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Pegolo, Sara (2010) Enzimi farmaco-metabolizzanti epatici in specie di interesse veterinario. [Tesi di dottorato]

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Abstract (inglese)

In veterinary medicine, the characterisation of the P450 isoenzymes is still incomplete and moreover, the substrates used were selected on the basis of the available knowledge from experiments in human or laboratory species without any kinetic or inhibition study (Fink-Gremmels, 2008). Defining the contribution of a P450 isoform in the metabolism of a specific drug is of great interest not only for veterinary pharmacology and toxicology but also for human health, for the potential presence of toxic residues in food animal products.
During the PhD course, projects dealing with the evaluation of cytochrome P450 activities in veterinary species have been developed. The aim was to increase knowledge about drug metabolizing enzymes in veterinary species and about the modulation of their activity. The modulation may be due to factors as breed but also exposure to environmental contaminants or somministration of illicit drugs used to enhance growth and consequently increase profit (Johnson, 2007). Data collected from these in vitro studies can be actually used to evaluate the effects of drug-drug interactions and for the plan of experimental projects aiming to identify in vivo markers of exposure or treatment.
I) Determination of CYP1A and CYP2C activities in bovine liver. In this study, accuracy, precision, LOD and LOQ of High Performance Liquid Chromatography (HPLC) methods previously developed in the lab for the evaluation of ethoxyresorufin-O-deethylase (EROD) e tolbutamide methyl-hydroxylase (TMOH) activities, have been determined. The aim was to calculate the enzyme kinetic parameters: respectively 0.23 ± 0.051 and 1010 ± 155.7 μM for Km and 0.488 ± 0.035 and 0.089 ± 0.006 nmol/min/mg protein for Vmax. The methods were proved to be so sensitive to determine also very low levels of enzyme activity as those of veal calves fed with milk replacers and low iron content diet. Finally, to verify the presence of intra-specific differences in enzyme activity, EROD and TMOH were determined with liver microsomes from Charolais (CH), Blonde D’Aquitaine (BD) and Piedmontese (PM). The results of EROD evidenced higher activity in CH vs PM (p<0.05). So, for the first time, the presence of breed differences in this enzyme activity was established, confirming also what reported by other authors for CYP3A-dependent activities (Dacasto et al., 2005). These differences may influence bioavailability and clinical efficacy of xenobiotics (Sallovitz et al., 2002) and may be of particular interest in veterinary species for the potential presence of toxic residues in food animal products.
II) Testosterone hydroxylation in bovine liver: enzyme kinetic and inhibition study. This study evaluated, by HPLC analysis, the kinetic of testosterone (TST) hydroxylase activities in vitro, with liver microsomes from cattle. Kinetic parameters for 6b–, 16b– and 2b –TST hydroxylase activities (OHT) were 93.4±13.8, 36.4±6.1 and 110.8±15.2 ±M respectively for Km and 0.558±0.03, 0.280±0.013 and 0.338±0.017 nmol/min/mg protein for Vmax.. Moreover, chemical inhibition studies with a CYP3A inhibitor (ketoconazole) and CYP2B inhibitors (orphenadrine and 9-ethynylphenanthrene) were performed to establish the involvement of CYP3A and potentially of CYP2B in these enzyme reactions. To further confirm the results obtained, an anti-peptide antibody against bovine CYP3A4 was also used. The antibody specificity with bovine liver microsomes was evaluated and then immunoinhibition studies were conducted, evidencing > 90% inhibition for 16b– and 2b –OHT activities and > 80% for 6b–OHT. These results seemed to suggest the predominant involvement of CYP3A in the production of the three main TST-hydroxylated metabolites in bovine liver while CYP2B seemed to be not involved.
III) Effects of illicit treatments on CYP3A in bovine liver and in primary cultures of bovine hepatocytes. These experiments intended to prove the applicability of the HPLC method and TST substrate for evaluating CYP3A activity, aiming to actually verify illicit treatments effect and collect more data respect to previous studies in veal calf and beef cattle.
In the first experiment, 6b-, 16b- and 2b-OHT were determined in bovine treated with dexamethasone (D) and dexamethasone+estradiol (DE). The results obtained evidenced a significant induction for 6b- and 16b-OHT in D and DE vs control (K, p<0.05) and for 2b–OHT in D and DE vs K (p<0.05 and p<0.01, respectively), confirming what reported for human (McCune et al., 2000). These results were confirmed by Immunoblotting which evidenced increasing in CYP3A protein expression in D and D+E vs K (p<0.01 and p<0.05, respectively).
In the second experiment, 6b-, 16b- and 2b-OHT were determined in bovine hepatocytes after 24 h incubation with boldenone (B), androsta-1,4-diene-3,17-dione (A) and B + A. The results showed an inhibitory trend in hepatocytes incubated with growth promoters vs controls (K). In particular, 6b and 16b OHT were inhibited in A and B vs K while 2b-OHT in A vs K (p<0.05). At the protein level instead, no significant difference was found in CYP3A expression (Immunoblotting). The inhibitory effect observed may be due to the high doses used; inhibitory/toxic effects of high doses of inducing agents were evidenced for instance by Kostrubsky et al. (1999) who used human hepatocytes to study induction of cytochrome P450, stressing the importance of large dose-response studies as well as the need to assess toxicity in these investigations.
The results obtained in these experiments confirmed the modulation of expression and regulation of cytochrome P450 enzymes by estrogens, corticosteroids and anabolic steroids. There is the need however, to explain deeply for bovine the mechanism through that these compounds act at pre- and post-transcriptional level.
IV) Determination of CYP1A activity in the liver of Zosterisessor ophiocephalus as biomarker of pollution in the Venice Lagoon. Recently, it was proved that biomarkers (BM) are very useful to evidence early biological changes in environmental pollution. One of the most common BM used in fishes is the induction of the P450 system and in particolar ethoxyresorufin O-deethylase activity (EROD) is a marker of fish exposure to potentially toxic compounds, i.e. poli-chlorinated biphenils and polycyclic aromatic hydrocarbons (Burgeot et al., 1994). The aim of this study was to evaluate by HPLC EROD activity in Zosterisessor ophiocephalus, a benthic fish that may represent an useful bioindicator of environmental stress in the Venice Lagoon. Fishes were collected in spring and autumn in three different areas of the Venice Lagoon: Porto Marghera (PM), Valle di Brenta (VB) and Porto Canale (PC); the samples were then classified in females, males and sneakers (small males, < 1 years-old).
Factorial analysis of EROD activity results evidenced that site, fish category and season were significant (p<0,001), and the interactions category*site and category *season as well (p<0,001). Considering site effect in particular, in PM EROD activity values were significantly higher than in VB and in PC (p<0,01 and p<0,001, respectively) and in VB higher than in PC (p<0,01). These results were in agreement with the available data relative to persistent organic pollutants (POPs) concentration (expressed as enrichment factor, EF) in the sediments of the Venice Lagoon, that showed major contamination in the area close to Porto Marghera (EF>12), intermediate in the area of Valle di Brenta (EF=5-12) and low around Porto Canale (EF=1-5; Guerzoni et al., 2004). However, site effect depended on the fish category and in particular differences were found between males and females, due more probably to the analyzed samples than to real differences in induction. From these results, EROD activity may be considered an useful biomarker even if, considering the multifactorial response of individuals, it is important to use several significant biomarkers to accurately evaluate the effects of environmental pollution in the aquatic ecosystem.
V) Luminescence high-throughput methods for determining CYP3A and CYP2C activities in horse liver. In the last part of the thesis, results of kinetic and inhibition studies to evaluate CYP2C and CYP3A activities in horse liver through Glo assays were reported. The aim was to evaluate the performances of this technique for drug metabolism or drug-drug interaction studies. Enzyme kinetic parameters for CYP3A and CYP2C activities were respectively 14.5 ± 7.3 and 175.9 ± 16.2 μM for Km and 0.022 ± 0.0004 and 0.025 ± 0.0009 nmol/min/mg protein for Vmax. Ketoconazole (CYP3A inhibitor) evidenced IC50 values of 0.035 μM, confirming good specificity of the luciferin (L)-derivative substrate used for CYP3A (L-IPA). Sulfaphenazole (CYP2C inhibitor) evidenced IC50 values of 47.2 μM, suggesting the need to conduct further studies to verify substrate specificity (L-H), for instance using other selective inhibitors for the CYP2C subfamily as ibuprofen or diclofenac. Luminescence methods allowed to analyse many samples in short time, to monitor more than one isoform simultaneously in the same plate and showed good sensitivity confirmed by LOD values: 0.2 and 0.11 nM for L-H and L-IPA, respectively. So, these results may represent a good starting point to apply this technique in drug metabolism and drug-drug interaction studies in veterinary species

Abstract (italiano)

Nel corso dei tre anni di dottorato sono stati sviluppati progetti relativi alla valutazione dell’attività epatica di isoforme di citocromo P450 in specie di interesse veterinario. In medicina veterinaria, la caratterizzazione del sistema P450 è ancora incompleta; inoltre, i substrati utilizzati sono stati selezionati sulla base delle conoscenze disponibili a partire da esperimenti condotti nell’uomo o nelle specie di laboratorio senza studi di cinetica enzimatica o di inibizione (Fink-Gremmels, 2008). Definire il contributo di un’isoforma di citocromo P450 nel metabolismo di un farmaco specifico è importante non solo per la farmacologia e la tossicologia veterinarie ma anche per la salute dell’uomo, per la possibile presenza di residui nei prodotti di origine animale.
L’obiettivo della presente tesi di dottorato è stato dunque quello di aumentare le conoscenze sugli enzimi che metabolizzano i farmaci in specie di interesse veterinario e sulla modulazione della loro attività. Tale modulazione può essere dovuta a fattori come la razza ma anche all’esposizione ad inquinanti ambientali oppure alla somministrazione di sostanze illecite utilizzate allo scopo di determinare incremento ponderale, riduzione degli indici di conversione alimentare e quindi aumento complessivo del reddito (Johnson, 2007). Le informazioni ottenute con tali studi in vitro dunque possono essere utili per valutare l’effetto di interazioni tra farmaci e per il disegno sperimentale di progetti volti all’identificazione di marker in vivo di esposizione o trattamento.
I) Valutazione dell’attività di CYP1A e CYP2C nel fegato di bovino. Nel presente lavoro, sono stati verificati accuratezza, precisione, LOD e LOQ di metodi in High Performance Liquid Chromatography (HPLC) precedentemente messi a punto nel laboratorio per la valutazione dell’attività di etossiresorufina-O-deetilasi (EROD) e tolbutamide metil-idrossilasi (TMOH) in microsomi epatici di bovino allo scopo di determinare i parametri di cinetica enzimatica: rispettivamente 0,23 ± 0,051 e 1010 ± 155,7 μM per la Km e 0,488 ± 0,035 e 0,089 ± 0,006 nmol/min/mg proteina per laVmax. La sensibilità dei metodi messi a punto ha permesso di valutare anche livelli di attività enzimatica molto bassi come quelli dei vitelli a carne bianca che vengono alimentati con una dieta a base di sostitutivi del latte e basso contenuto di ferro. Infine, per verificare l’esistenza di differenze intra-specifiche nell’attività enzimatica, le attività di EROD e TMOH sono state determinate utilizzando microsomi epatici di bovini di razza Charolais (CH), Blonde D’Aquitaine (BD) e Piemontese (PM). I risultati ottenuti per l’attività di EROD hanno evidenziato una maggiore attività nei bovini di razza CH vs PM (p<0,05). E’ stata dunque dimostrata, per la prima volta, l’esistenza di differenze intra-specifiche dovute alla razza relative a questa attività enzimatica, confermando quanto evidenziato da altri autori in relazione ad attività CYP3A-dipendenti (Dacasto et al., 2003). Tali differenze potrebbero influenzare la biodisponibilità e l’efficacia clinica di xenobiotici (Sallovitz et al., 2002) e potrebbero essere di particolare interesse nelle specie di interesse veterinario per l’ipotetica presenza di residui potenzialmente tossici negli alimenti di origine animale. Per quanto riguarda invece l’attività di TMOH non sono state evidenziate differenze statisticamente significative.
II) Valutazione dell’attività di idrossilazione del testosterone nel fegato di bovino: studio di cinetica enzimatica e di inibizione. In questo studio è stata valutata, tramite analisi in HPLC, la cinetica delle reazioni di idrossilazione del testosterone (TST) in vitro, con microsomi epatici di bovino. I parametri di cinetica enzimatica per le attività di 6b–, 16b– e 2b –TST idrossilasi (OHT) sono risultati 93,4±13,8, 36,4±6,1 e 110,8±15,2 ±M rispettivamente, per la Km e 0,558±0,03, 0,280±0,013 e 0,338±0,017 nmol/min/mg proteina per la Vmax.. Inoltre sono stati effettuati degli studi di inibizione chimica con inibitori di CYP3A (chetoconazolo) e di CYP2B (orfenadrina e 9-etinilfenantrene) per definire il coinvolgimento di CYP3A e potenzialmente di CYP2B in queste reazioni enzimatiche. I risultati ottenuti sono stati ulteriormente confermati con l’impiego di un anticorpo anti-peptide contro CYP3A4 di bovino. Dopo aver valutato la sua specificità con microsomi epatici di bovino, sono stati effettuati degli studi di immunoinibizione, che hanno evidenziato un’inibizione > 90% per le attività di 16b– e 2b –OHT e > 80% per 6b–OHT. Nel complesso, questi risultati sembrerebbero suggerire il coinvolgimento predominante di CYP3A nella produzione dei tre principali metaboliti del TST nel fegato di bovino mentre CYP2B non sembrerebbe essere coinvolto.
III) Effetti di trattamenti illeciti su CYP3A nel fegato del bovino da carne e in colture primarie di epatociti di bovino. L’obiettivo principale di entrambe le prove sperimentali descritte è stato quello di dimostrare l’applicabilità del metodo HPLC e del substrato TST per la valutazione dell’attività enzimatica CYP3A-dipendente, allo scopo di verificare l’effetto del trattamento e di acquisire ulteriori evidenze sperimentali rispetto ai risultati di studi precedentemente coinvolti dal nostro gruppo di ricerca sul vitello a carne bianca e sul vitellone.
In un primo esperimento, sono state determinate le attività di 6b-, 16b- e 2b-OHT in microsomi epatici di bovini trattati con desametazone (D) e desametazone + estradiolo (DE). I risultati ottenuti hanno evidenziato un’induzione statisticamente significativa nelle attività di 6b- e 16b-OHT in D e DE vs controlli (K, p<0,05) e nell’attività di 2b–OHT in D e DE vs K (p<0,05 e p<0,01, rispettivamente), confermando quanto riportato in letteratura per l’uomo (McCune et al., 2000). Tali risultati sono stati convalidati ulteriormente dall’analisi in Immunoblotting che ha evidenziato un aumento dell’espressione di CYP3A in D e D+E vs K (p<0,01 e p<0,05, rispettivamente).
In un secondo esperimento, sono state determinate le attività di 6b-, 16b- e 2b-OHT in epatociti di bovino dopo 24 h di incubazione con boldenone (B), androsta-1,4-diene-3,17-dione (A) e B + A. I risultati ottenuti hanno evidenziato un trend inibitorio negli epatociti incubati con promotori di crescita rispetto a K. In particolare, le attività di 6b e 16b OHT sono state inibite in A e B vs K mentre l’attività di 2b-OHT in A vs K (p<0,05). A livello di proteina invece, non è stata riscontrata alcuna differenza statisticamente significativa nell’espressione di CYP3A (Immunoblotting). L’effetto inibitorio osservato potrebbe essere dovuto alle dosi utilizzate; un caso di effetto inibitorio/tossico di alte dosi di sostanze inducenti è riportato da Kostrubsky et al. (1999) che hanno utilizzato epatociti di uomo per studiare l’induzione del sistema citocromo P450 evidenziando la necessità di effettuare degli studi dose-risposta in un ampio range di concentrazioni delle sostanze utilizzate e di valutarne la tossicità.
Nel complesso, i risultati ottenuti in questi due esperimenti hanno confermato la modulazione da parte di estrogeni, corticosteroidi ed anabolizzanti dell’espressione e la regolazione degli enzimi citocromo P450-dipendenti. Chiaramente, rimane comunque la necessità di spiegare più approfonditamente per quanto riguarda il bovino i meccanismi tramite i quali queste sostanze agiscono sia a livello pre-trascrizionale che post-trascrizionale.
IV) Valutazione dell’attività di CYP1A nel fegato di Zosterisessor ophiocephalus come biomarcatore di inquinamento nella laguna di Venezia. Recentemente, è stato dimostrato che i biomarcatori (BM) sono molto utili per rilevare dei cambiamenti biologici precoci nell’inquinamento ambientale. Uno dei BM più comunemente usati nei pesci è l’induzione dell’attività di etossiresorufina-O-deetilasi (EROD) che è un indicatore dell’esposizione dell’organismo a composti potenzialmente tossici, come ad esempio i policloro-bifenili e gli idrocarburi aromatici policiclici (Burgeot et al., 1994). Di conseguenza, lo scopo del presente lavoro è stato quello di valutare l’attività di EROD tramite HPLC in Zosterisessor ophiocephalus, una specie bentonica che date le sue caratteristiche, può rappresentare un utile indicatore biologico dei livelli di stress ambientale presente nella Laguna di Venezia. I pesci sono stati raccolti in primavera ed in autunno in tre aree della Laguna di Venezia: Porto Marghera (PM), Valle di Brenta (VB) e Porto Canale (PC); i campioni sono stati poi suddivisi in femmine, maschi e sneakers (maschi giovani). L’analisi fattoriale ha evidenziato la significatività dei fattori sito, categoria e stagione (p<0,001) ma anche delle interazioni categoria*sito e categoria*stagione (p<0,01). Per quanto riguarda l’effetto del sito in particolare, PM possedeva valori di attività di EROD significativamente più elevati rispetto a VB e PC (p<0,01 e p<0,001, rispettivamente) e VB rispetto a PC (p<0,001). Tali risultati sembrerebbero essere in accordo con i dati disponibili relativi alla concentrazione di inquinanti organici persistenti (POP) espressa come fattore di arricchimento (EF) nei sedimenti della Laguna di Venezia, i quali indicano una contaminazione maggiore nell’area circostante a Marghera (EF>12), intermedia nei pressi di Valle di Brenta (EF=5-12) e ridotta nel territorio contiguo al sito di Porto Canale (EF=1-5; Guerzoni et al., 2004). L’effetto del sito dipendeva comunque dalla categoria di animali considerata ed in particolare sono state evidenziate delle differenze tra maschi e femmine, dovute probabilmente comunque al campione analizzato più che a differenze reali in termini di induzione. Dai risultati ottenuti, l’attività di EROD è da considerarsi un buon biomarcatore anche se, considerando la natura multifattoriale della risposta dell’individuo, è necessario l’utilizzo congiunto di più biomarcatori significativi per effettuare una valutazione accurata degli effetti dell’inquinamento nell’ecosistema acquatico.
V) Messa a punto di metodi high-throughput in luminescenza per la valutazione dell’attività di CYP3A e di CYP2C nel fegato di cavallo. Nell’ultimo capitolo della tesi, sono riportati i risultati relativi agli studi di cinetica enzimatica e di inibizione chimica volti alla valutazione delle attività di CYP2C e CYP3A nel fegato di cavallo mediante l’utilizzo di saggi Glo. Lo scopo è stato quello di valutare le performance di questa tecnologia allo scopo di applicarla in studi di metabolismo e di interazioni tra farmaci. I parametri di cinetica enzimatica per le attività di CYP3A e di CYP2C sono risultati rispettivamente 14,5 ± 7,3 e 175,9 ± 16,24 μM per la Km e 0,022 ± 0,004 e 0,025 ± 0,0009 nmol/min/mg proteina per la Vmax. Chetoconazolo (inibitore di CYP3A) ha evidenziato un valore di IC50 pari a 0,035 μM, confermando quindi una buona specificità del substrato luciferina (L)-derivato utilizzato per CYP3A (L-IPA). Sulfafenazolo (inibitore di CYP2C) ha evidenziato un valore di IC50 pari a 47,2 μM, suggerendo dunque la necessità di effettuare ulteriori studi volti a verificare la specificità di substrato (L-H), ad esempio utilizzando altri inibitori selettivi per tale sottofamiglia come l’ibuprofene o il diclofenac. I metodi in luminescenza messi a punto permettono di analizzare un numero elevato di campioni in tempi brevi, di monitorare più di un’isoforma contemporaneamente nella stessa piastra e sono caratterizzati da una buona sensibilità, confermata dai valori di LOD ottenuti: 0,2 e 0,11 nM per L-H e L-IPA, rispettivamente. I risultati ottenuti dunque possono costituire un ottimo punto di partenza per poter applicare la tecnologia di tali saggi in studi relativi alle specie di interesse veterinario con vantaggi di costi e tempi di realizzazione delle analisi

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Tipo di EPrint:Tesi di dottorato
Relatore:Capolongo, Francesca
Dottorato (corsi e scuole):Ciclo 22 > Scuole per il 22simo ciclo > SCIENZE VETERINARIE > SANITA' PUBBLICA E PATOLOGIA COMPARATA
Data di deposito della tesi:NON SPECIFICATO
Anno di Pubblicazione:25 Gennaio 2010
Parole chiave (italiano / inglese):citocromo P450; HPLC; cinetica enzimatica; validazione; inquinamento ambientale; trattamenti illeciti; metodi luminescenza
Settori scientifico-disciplinari MIUR:Area 07 - Scienze agrarie e veterinarie > VET/07 Farmacologia e tossicologia veterinaria
Struttura di riferimento:Dipartimenti > pre 2012 - Dipartimento di Sanità pubblica, Patologia comparata ed Igiene veterinaria
Codice ID:2453
Depositato il:28 Ott 2010 17:12
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Le url contenute in alcuni riferimenti sono raggiungibili cliccando sul link alla fine della citazione (Vai!) e tramite Google (Ricerca con Google). Il risultato dipende dalla formattazione della citazione.

Abraham, G., Gottschalk, J., Ungemach, F.R., 2004. Possible role of dexamethasone in sensitizing the beta-2-adrenergic receptor system in vivo in calves during concomitant treatment with clenbuterol. Pharmacology 72, 196-204. Cerca con Google

Addison, R. F., Edwards, A. J., 1988. Hepatic microsomal mono-oxygenase activity in flounder Platichthys flesus from polluted sites in Langesundfjord and from mesocosms experimentally dosed with diesel oil and copper. Marine Ecology Progress Series 46, 51-54. Cerca con Google

Aiba, T., Takehara, Y., Okuno, M., Hashimoto, Y., 2003, Poor correlation between intestinal and hepatic metabolic rates of CYP3A4 substrates in rats. Pharm Res 20, 745-748. Cerca con Google

Akingbemi, B.T., 2005. Estrogen regulation of testicular function. Reproductive Biology and Endocrinology 51, 1-13. Cerca con Google

Al Katheeri, N.A., Wasfi, I.A., Lambert, M., Giuliano Albo, A., Nebbia, C., 2006. In vitro and in vivo metabolism of dexamethasone in the camel. Veterinary journal 172, 532-543. Cerca con Google

Arts, C.J.M., Schilt, R., Van Ginkel, L.A., 1996. Boldenone is a naturally occurring anabolic steroid in cattle. Proceedings of the EuroResidue III, Haagsma, N., Ruiter, A., Eds., Veldhoven, The Netherlands, 212-216. Cerca con Google

Backes W.L., 1993. NADPH-cytochrome P450 reductase: function. In: J.B. Schemkmann and H. Greim, Editors, Handbook of Experimental Pharmacology: Cytochrome P450, Springer, Berlin, NY (1993), pp. 15–34. Cerca con Google

Baliharova, V., Velik, J., Savlik, M., Szotakova, B., Lamka, J., Tahotna, L., Skalova, L., 2004, The effects of fenbendazole, flubendazole and mebendazole on activities of hepatic cytochromes P450 in pig. J Vet Pharmacol Ther 27, 85-90. Cerca con Google

Ball, G.F., Balthazard, J., 2004. Hormonal regulation of brain circuits mediating male sexual behavior in birds. Physiology and Behavior 83, 329-346. Cerca con Google

Bergmeyer H.U., Bernt E., Hess B. (1963) Lactic dehydrogenase. In: H.U. Bergmeyer (Eds.), Methods of Enzymatic Analysis. Academic Press, New York, pp.736-741. Cerca con Google

Bernhardt, R., 2006. Cytochromes P450 as versatile biocatalysts. Journal of Biotechnology 25, 128-45. Cerca con Google

Burnstein, K.L., Maiorino, C.A., Dai, J.L., Cameron, D.J., 1995. Androgen and glucocorticoid regulation of androgen receptor .cDNA expression. Molecular and Cellular Endocrinology II 5, 1777186 Cerca con Google

Bernstein A.G., A. Barbante, G. Ferrari, A. Marcomini, S. Guerzoni and R. Zonta (2002). Sources and occurrence of Persistent Toxic Substances (PTS) in the Lagoon of Venice (Italy). Paper presented at the 1st UNEP Regional Workshop on Assessment of PTS sources and concentrations in the environment, 4-6 February 2002, Athens (Greece). Cerca con Google

Bjornsson, T.D., Callaghan, J.T., Einolf, H.J., Fischer, V., Gan, L., Grimm, S., Kao, J., King, S.P., Miwa, G., Ni, L., Kumar, G., MacLeod, J., Obach, R.S., Roberts, S., Roe, A., Shah, A., Snikeris, F., Sullivan, J.T., Tweedie, D., Vega, J.M., Walsh, J., Wrighton, S. A., 2003. The conduct of in vitro and in vivo drug–drug interaction studies: A pharmaceutical research and manufacturers of America (PhRMA) perspective. Drug Metabolism and Disposition 31, 815–832. Cerca con Google

Bogaards, J. J. P., Bertrand, M., Jackson P., Oudshoorn, M. J., Weaver, R. J., Van Bladeren, P. J., Walther, B., 2000. Determining the best animal model for human cytochrome P450 activities: a comparison of mouse, rat, rabbit, dog, micropig, monkey and man. Xenobiotica 30, 1131-1152. Cerca con Google

Brandin, H., Viitanen, E., Myrberg, O., Arvidsson, A.K., 2007, Effects of herbal medicinal products and food supplements on induction of CYP1A2, CYP3A4 and MDR1 in the human colon carcinoma cell line LS180. Phytother Res 21, 239-244. Cerca con Google

Burgeot, T., Bocquéné, G., Truquet, P., Le Dean, L., Galgani, F., 1994. Induction of EROD activity in red mullet (Mullus barbatus) along the French Mediterranean coasts. Science of the Total Environment 142, 213-220. Cerca con Google

Burgeot, T., Bocquènè, G., Porte, C., Dimeet, J., Santella, R.M. Garcia de la Parra, L.M., Pfhol-Leszkowicz, A., Raoux, C., Galgani, F., 1996. Bioindicators of pollutant exposure in the northwestern Mediterranean Sea. Marine Ecology progress Series 131, 125-141. Cerca con Google

Burke, M., Mayer, R.T., 1974. Ethoxyresorufin: direct fluometric assay of a microsomal O-dealkylation which is preferentially inducible by 3-methylchloranthrene. Drug Metabolism and Disposition 2, 583-588. Cerca con Google

Cali , J.J., Ma, D., Sobol, M., Simpson, D.J, Frackman, S., Good, T.D., Daily , W.J., Liu, D ., 2006. Luminogenic cytochrome P450 assays. Expert Opinion on Drug Metabolism & Toxicology 2, 629-645. Cerca con Google

Cantiello, M., Carletti, M., Dacasto, M., Martin, P.G.P., Pineau, T., Capolongo, F., Gardini, G., Nebbia, C., 2008. Cytochrome P450 inhibition profile in liver of veal calves administered a combination of 17-estradiol, clenbuterol, and dexamethasone for growth-promoting purposes. Food and Chemical Toxicology, doi: 10.1016/j.fct.2008.05.018. Cerca con Google

Cantiello, M., Giantin, M., Carletti, M., Lopparelli, R.M., Capolongo, F., Lasserre, F., Bollo, E., Nebbia, C., Martin, P.G., Pineau, T, Dacasto, M., 2009. Effects of dexamethasone, administered for growth promoting purposes, upon the hepatic cytochrome P450 3A expression in the veal calf. Biochemical pharmacology 77, 451-463. Cerca con Google

Capolongo, F., Dacasto, M., Carletti, M., Nebbia, C., Merlanti, R., Montesissa, C., 2003. Effetti di alcuni trattamenti illeciti sul metabolismo ossidativo P450-dipendente nel fegato del vitello a carne bianca: risulatti preliminari. Atti S.I.S. Vet., LVIII, 130. Cerca con Google

Capponi, L., Schmitz, A., Thormann, W., Theurillat, R., Mevissen, M., 2009. In vitro evaluation of differences in phase 1 metabolism of ketamine and other analgesics among humans, horses, and dogs. American Journal of Veterinary Research 70, 777-786. Cerca con Google

Chauret, N., Gauthier, A., Martin, J., Nicoll–Griffith, D.A., 1997. In vitro comparison of cytochrome P450-mediated metabolic activities in human, dog, cat and horse. Drug Metabolism and Disposition 25, 1130–1136. Cerca con Google

Chesne, C., Guyomard, C., Guillouzo, A., Schmid, J., Ludwig, E., Sauter, T., 1998, Metabolism of Meloxicam in human liver involves cytochromes P4502C9 and 3A4. Xenobiotica 28, 1-13. Cerca con Google

Choo, J.J., Emery, P.W., Rotwell, N.J., 1991. Dose-dependent effects of a steroid, nandrolone phenylpropionate (Durabolin), on body composition and muscle protein metabolism in female fats. Annals of nutrition and metabolism 35, 141-147. Cerca con Google

Casarett, L.J., Doull, J., 2001. Biotransformation of xenobiotics, Induction of Cytochrome P450. In: C.D. Klaassen (Eds.), Toxicology: The Basic Science Of Poisons. McGraw-Hill, New York, pp. 135-136. Cerca con Google

Chiesara, E., Radice, S., 1997. Metabolismo dei farmaci, Induzione e Inibizione farmaco-metabolica. In: F. Clementi e G.Fumagalli (Eds.). Farmacologia Generale e Molecolare,. UTET, Torino, pp. 458-472. Cerca con Google

Clarke, M.L., Harvey, D.G., Humphreys, J.R. (Edizione 1981) In: Ballière and Tindall, Veterinary Toxicology, London. Cerca con Google

Clarke, S.E., 1998. In vitro assessment of human cytochrome P450. Xenobiotica 28, 1167-202. Cerca con Google

Commissione dell’Unione Europea, Regolamento del Consiglio 2377/90/CE. Gazzetta Ufficiale, L224 (1990) Cerca con Google

Commissione dell’Unione Europea, Direttiva Comunitaria 2003/74/CE. Official Journal of the European Communities, L 262 (2003) 17-21. Cerca con Google

Commissione dell’Unione Europea, Direttiva del Consiglio 96/23/CE. Official Journal of the European Communities, L125 (1996) 10 Cerca con Google

Cohen, J., 1988. Statistical Power Analysis for the Behavioural Sciences 2nd Edition. Lawrence Erlbaum Associates. Cerca con Google

Courtheyn, D., Le Bizec, B., Brambilla, G., De Brabander, H.F., Cobbaert, E., Van de Wiele, M., Vercammen, J., De Wasch, K., 2002. Recent developments in the use and abuse of growth promoters. Analytica Chimica Acta 473, 71-82. Cerca con Google

Cribb, A., Nuss, C., Wang, R.W., 1995. Antipeptide antibodies against overlapping sequences differentially inhibit human CYP2D6. Drug Metabolism and Disposition, 23, 671–675. Cerca con Google

Cuzzocrea, S., Bruscoli, S., Crisafulli, C., Mazzon, E., Agostini, M., Muià, C., Esposito, E., Di Virgilio, R., Meli, R., Vegeto, E., Maggi, A., Riccardi, C., 2007. Estrogen receptor antagonist fulvestrant (ICI 182,780) inhibits the anti-inflammatory effect of glucocorticoids. Molecular Pharmacology 71, 132-144. Cerca con Google

Dacasto, M., Eeckhoutte, C., Capolongo, F., Dupuy, J., Carletti, M., Calle´ja, C., Nebbia, C., Alvinerie, M., Galtier, P., 2005. Effect of breed and gender on bovine liver cytochrome P450 3A (CYP3A) expression and inter-species comparison with other domestic ruminants. Veterinary Research 36, 179–190. Cerca con Google

Daxenberger, A., Ibarreta, D., Meyer, H.H., 2001. Possible health impact of animal oestrogens in food. Human Reproduction Update. 7, 340-55. Cerca con Google

Derendorf, H., Hochhaus, G., 1995. Handbook of pharmacokinetic/pharmacodinamic correlation. CRC Press, USA. Cerca con Google

Doehmer, J., Tewes, B., Klein, K.U., Gritzko, K., Muschick, H., Mengs, U., 2008, Assessment of drug-drug interaction for silymarin. Toxicol In Vitro 22, 610-617. Cerca con Google

Donato, M.T., 2004. Qué es el citocromo P-450 y cómo funziona. In: Cascales Angosto M, Gómez- Lechón MJ, Citocromo P-450, Istituto de España, Real Accademia Nacional de Farmacia, Realigraf S.A., Madrid, España Cerca con Google

Dupuy, J., Escudero, E., Eeckhoutte, C., Sutra, J.F., Galtier, P., Alvinerie, M., 2001, In vitro metabolism of 14C-moxidectin by hepatic microsomes from various species. Vet Res Commun 25, 345-354. Cerca con Google

Eeckhoutte, C., Albo, A.G., Carletti, M., Giaccherino, A.R., Galtier, P., Nebbia, C., Dacasto, M., 2002. Time-dependent variations of drug-metabolising enzyme activities (DMEs) in primary cultures of rabbit hepatocytes. Toxicology In Vitro 16, :375-382. Cerca con Google

Eggens, M., Bergman, A., Vethaak, D., 1995. Seasonal variation of hepatic EROD activity in flounder (Platichthys flesus) in the Dutch Wadden Sea. Marine Environmental Research 39, 231 - 234. Cerca con Google

Ekins, S., VandenBranden, M., Ring, B.J., Wrighton, S.A., 1997. Examination of purpored probes of human CYP2B6. Pharmacogenetics 7, 165-179. Cerca con Google

Elbarbry, F., Wilby, K., Alcorn, J., 2006. Validation of a HPLC method for the determination of p-nitrophenol hydroxylase activity in rat hepatic microsomes. Journal of Chromatography B 834, 199-203. Cerca con Google

El-Sankary, W., Bombail, V., Gibson, G.G., Plant, N., 2002. Glucocorticoid-mediated induction of CYP3A4 is decreased by disruption of a protein: DNA interaction distinct from the pregnane X receptor response element. Drug Metabolism and Disposition 30, 1029-1034. Cerca con Google

Everaarts, J. M., Shugart, L. R., Gustin, M. K., Hawkins, W. E., Walker, W. W., 1993. Biological markers in fish: DNA integrity, hematological parameters and liver somatic index. Marine Environmental Research 35, 101–107. Cerca con Google

Flaws, J.A., Bush, T.L., 1998. Racial differences in drug metabolism: an explanation for higher breast cancer mortality in blacks? Medical Hypotheses 50, 327-329. Cerca con Google

Fletcher, G. L., King, M. J., Kiceniuk, J. W., Addison, R. F., 1982. Liver hypertrophy in winter fluonder following exposure to environmentally oiled sediments. Comparative Biochemistry and Physiology - Part C 73, 457–462. Cerca con Google

Fink-Gremmels, J., 2008. Implications of hepatic cytochrome P450-related biotransformation processes in veterinary sciences. European Journal of Pharmacology 585, 502-509. Cerca con Google

Franco, A., Malavasi, S., Pranovi, F., Nasci, C., Torricelli, P., 2002. Ethoxyresorufin O-deethylase (EROD) activity and fluctuating asymmetry (FA) in Zosterisessor ophiocephalus (Teleostei, Gobiidae) as indicators of environmental stress in the Venice Lagoon. Journal of Aquatic Ecosystem Stress and Recovery 9, 239-247 Cerca con Google

Galgani, F., Bocquéné, G., Luçon, M., Grzebyk, D., Letrouit, F., Claisse, D., 1991. EROD measurements in fish from the northwest part of France. Marine Pollution Bulletin 22, 494-500. Cerca con Google

Galgani, F., Payne, J. F., 1991. Biological effects of contaminants: microplate method for measurement of ethoxyresorufin-O-deethylase (EROD) in fish. ICES Tech. Marine Environmental Science 13, 1-11. Cerca con Google

Galgani, F., Bocquene, G., Truquet, P., Burgeot, T., Chiffoleau, J.F., Claisse, D., 1992. Monitoring of pollutant biochemical effects on marine organisms of the French coasts. Oceanologica Acta 15, 355-364. Cerca con Google

Gentile, D.M., Tomlinson, E.S., Maggs, J.L., Park, B.K., Back, D.J., 1996. Dexamethasone metabolism by human liver in vitro. Metabolite identification and inhibition of 6-hydroxylation. Journal of Pharmacology and Experimental Therapeutics 277, 105-112. Cerca con Google

Giantin, M., Carletti, M., Capolongo, F., Pegolo, S., Lopparelli, R.M., Gusson, F., Nebbia, C., Cantiello, M., Martin, P., Pineau, T., Dacasto, M., 2008. Effect of breed upon cytochrome P450 and phase II enzyme expression in cattle liver. Drug Metabolism and Disposition 36, 885-893. Cerca con Google

Giantin, M, Lopparelli, R.M., Zancanella, V.,Martin, P., Polizzi, A., gallina, G., Gottardo, F., Montesissa, C., Ravarotto, L., Pineau, T., Dacasto, M., 2009. Effects of illicit dexamethasone upon hepatic drug metabolizing enzymes and related transcription factors mRNAs and their potential use as biomarkers in cattle. Cerca con Google

Accettato per la pubblicazione in Journal of Agricultural and Food Chemistry. Cerca con Google

Greco, W.R., Hakala, M.T., 1979. Evaluation of methods for estimating the dissociation constant of tight binding enzyme inhibitors. The Journal of Biological Chemistry 254, 12104-12109. Cerca con Google

Griffin, D., 1999. Dietary management. In:Howard J., Current Veterinary Therapy: Food Animal Practice, Saunders Company, USA. Cerca con Google

Gonzalez, F.J., 1992. Human cytochromes P450: problems and prospects. Trends in pharmacological sciences 13, 346-52. Cerca con Google

Gorski JC, Vannaprasaht S, Hamman MA, Ambrosius WT, Bruce MA, Haehner-Daniels B, Hall SD., 2003. The effect of age, sex, and rifampin administration on intestinal and hepatic cytochrome P450 3A activity. Clin Pharmacol Ther. 74, 275-287. Cerca con Google

Guengerich, F.P., 1996. In vitro techniques for studying drug metabolism. Journal of Pharmacokinetics and Biopharmaceutics 24, 521-33. Cerca con Google

Guengerich, F.P., 1997. Comparison of catalytic selectivity of cytochrome P450 subfamily enzymes from different species. Chemico-Biological Interactions 106, 161-182. Cerca con Google

Guerzoni, S., Ferrari, G., Molinaroli, E., Rossini, P., Sarretta, A., 2004. Is the Lagoon of Venice healthy? A look at budgets and pathways of POPs in Venice. Organohalogenated Compounds 66, 1448–1454 Cerca con Google

Guo, Z., Raeissi, S., White, R.B., and Stevens, J.C., 1997. Orphenadrine and Methimazole Inhibit Multiple Cytochrome P450 Enzymes in Human Liver Microsomes. Drug Metabolism and Disposition 25, 390-393. Cerca con Google

Guo, L. Q, Taniguchi, M., Xiao, Y. Q, Baba, K., Ohta, T., and Yamazoe, Y., 2000. Inhibitory effect of natural furanocoumarins on human microsomal cytochrome P450 3A activity. The Japanese Journal of Pharmacology 82, 122–129. Cerca con Google

Gusson, F., Carletti, M., Giuliano Albo, A., Dacasto, M., Nebbia, C., 2006. Comparison of hydrolitic and conjugative biotransformations pathways in horse, cattle, pig, broiler chick, rabbit and rat liver subcellular fractions. Veterinary Research Commununication 30, 271–283. Cerca con Google

Hanioka, N., Tatarazako, N., Jinno, H., Arizono, K., Ando, M., 2000. Determination of cytochrome P4501A activities in mammalian liver microsomes by high–performance liquid chromatography with fluorescence detection. Journal of Chromatography B 744, 399–406. Cerca con Google

Hartl, M.G., 2002. Benthic Fish as Sentinel Organisms of Estuarine Sediment Toxicity. The Vienna Scxhool of marine Biology: A Tribute to Jörg Ott. Facultas Universitätsverlag: pp. 89-100. Cerca con Google

Hao, M., Zhao, Y., Chen, P., Huang, H., Liu, H., Jiang, H., Zhang, R., Wang, H., 2008, Structure-activity relationship and substrate-dependent phenomena in effects of ginsenosides on activities of drug-metabolizing P450 enzymes. PLoS ONE 3, e2697. Cerca con Google

He XJ, Ejiri N, Nakayama H, Doi K., 2005a. Changes in cytochrome P450 isozymes (CYPs) protein levels during lactation in rat liver. Exp Mol Pathol. 79, 224-228. Cerca con Google

He XJ, Ejiri N, Nakayama H, Doi K., 2005b. Effects of pregnancy on CYPs protein expression in rat liver. Exp Mol Pathol. 78, 64-70. Cerca con Google

Hellum, B.H., Nilsen, O.G., 2008, In vitro inhibition of CYP3A4 metabolism and P-glycoprotein-mediated transport by trade herbal products. Basic Clin Pharmacol Toxicol 102, 466-475. Cerca con Google

Hickman, D., Wang, J., Wang, Y., Unadkat, J.D., 1998. Evaluation of the selectivity of in vitro probes and suitability of organic solvents for the measurement of human cytochrome P450 monooxygenase activities. Drug Metabolism and Disposition 26, 207–215. Cerca con Google

Hijazi, Y., Boulieu, R., 2002. Contribution of CYP3A4, CYP2B6, and CYP2C9 isoforms to N-demethylation of ketamine in human liver microsomes. Drug Metabolism and Disposition 30, 853-8. Cerca con Google

Holdway, D. A., Brennan, S. E., Ahokas, J. T., 1994. Use of hepatic MFO and blood enzyme biomarkers in sand flathead (Platycephalus bassensis) as indicators of pollution in Port Phillip Bay, Australia. Marine Pollution Bulletin 28, 683-695. Cerca con Google

Hylland, K., Nissen-Lie, T., Christensen, P. G., Sandvik, M., 1998. Natural Modulation of Hepatic Metallothionein and Cytochrome P4501A in Flounder, Platichthys flesus L. Marine Environmental Research 46, 51-55. Cerca con Google

Ioannides, C., Parke, D.V., 1990. The cytochrome P450 I gene family of microsomal hemoproteins and their role in the metabolic activation of chemicals. Drug Metabolism Reviews 22, 1-85. Cerca con Google

Ioannides, C. Ed. (1996). Cytochromes P450 Metabolic and toxicological aspects. CRC Press, Boca Raton, FL. Cerca con Google

Ioannides, C., 1998. Effect of diet and nutrition on the expression of cytochrome P450. Xenobiotica 29, 109-154. Cerca con Google

Ioannides, C., 2006. Cytochrome P450 expression in the liver of food-producing animals. Current Drug Metabolism 7, 335-348. Cerca con Google

Istasse, I., De Haan, V., Van Enaeme, C., Buts, B., Baldwin, P., Gielen, M., Demeter, D., Bienfait, J.M., 1989. Effects of dexamethasone injections on performance in a pair of monozygotic cattle twins. Journal of Animal Physiology and Animal Nutrition 62,150-158 Cerca con Google

Johnson, B.J., Chung, K.Y. , 2007. Alterations in the physiology of growth of cattle with growth-enhancing compounds. Veterinary Clinics of North America: Small Animal Practise 23, 321-332. Cerca con Google

Kaltenbach, C.C., Dunn, T.G., 1984. Endocrinologia della riproduzione. In: Hafez E.S.E., Biologia e Tecnologia della Riproduzione nelle Specie Animali di Interesse Zootecnico, Editoriale Grasso, Bologna. Cerca con Google

Kamanga-Sollo, E., Pampusch, M.S., Xi, G., White, M.E., Hathaway, M.R., Dayton, W.R., 2004. IGF-I mRNA levels in bovine satellite cell cultures: effects of fusion and anabolic steroid treatment. Journal of Cell Physiology 201, 181-9. Cerca con Google

Kaneko, J.J., Harvey, J.W., Bruss, M.L., 1997. Appendix VIII. Blood analyte reference values in large animals. In: Kaneko, J.J., Harvey, J.W. and Bruss, M.L. (Eds.), Clinical Biochemistry of Domestic Animals, Fifth Edition. Academic press, San Diego, CA, pp.890-891. Cerca con Google

Kawamoto, T., Kakizaki, S., Yoshinari, K., Negishi, M., 2000. Estrogen activation of the nuclear orphan receptor CAR (constitutive active receptor) in induction of the mouse Cyp2b10 gene. Molecular Endocrinology 14, 1897-1905. Cerca con Google

Kennedy, S.W., Lorenzen, A., James, C.A., Collins, B.T., 1993. Ethoxyresorufin-O-deethylase and porphyrin analysis in chicken embryo hepatocyte cultures with a fluorescence multiwell plate reader. Analytical Biochemistry 211, 102-112. Cerca con Google

Kiyosawa, N., Kwekel, J.C., Burgoon, L.D., Williams, K.J., Tashiro, C., Chittim, B., Zacharewski, T.R., 2008. o,p'-DDT elicits PXR/CAR-, not ER-, mediated responses in the immature ovariectomized rat liver. Toxicological Sciences 101, 350-363. Cerca con Google

Kostrubsky, V.E, Ramachandran, V., Venkataramanan, R., Dorko, K., Esplen, J.E., Zhang, S., Sinclair, J.F., Wrighton, S.A., Strom, S.C., 1999. The use of human hepatocyte cultures to study the induction of cytochrome P-450. Drug Metabolism and Disposition 27, 887-894. Cerca con Google

Lapis, P., Pass, G.J., McKinnon, R.A., Stupans, I., 2000. Characterisation of tolbutamide hydroxylase activity in the common brushtail possum, (Trichosurus vulpecula) and koala (Phascolarctos cinereus): inhibition by the Eucalyptus terpene 1,8-cineole. Comparative Biochemistry and Physiology Part C 127, 351–357. Cerca con Google

Lasserre, P., Marzollo, A. (Eds.), 2000. The Venice Lagoon Ecosystem. Inputs and Interactions between Land and Sea. UNESCO, Paris and The Parthenon Publishing Group, Lanes and N.Y. Press, pp. 1-508. Cerca con Google

Leclercq, I., Desager, J.P., Vandenplas, C., Horsmans, Y., 1996. Fast determination of low–level cytochrome P450 1A1 activity by high–performance liquid chromatography with fluorescence or visible absorbance detection. Journal of Chromatography B 681, 227–232. Cerca con Google

Li, X., Makela, S., Streng, T., Santti, R., Poutanen, M., 2003, Phenotype characteristics of transgenic male mice expressing human aromatase under ubiquitin C promoter. J Steroid Biochem Mol Biol 86, 469-476. Cerca con Google

Lin, Y., Lu, P., Tang, C., Mei, Q., Sandig, G., Rodrigues, A.D., Rushmore, T.H., Shou, M., 2001. Substrate inhibition kinetics for cytochrome P450-catalyzed reactions. Drug Metabolism and Disposition 29, 368-374. Cerca con Google

Lin, H.L., Kent, U.M., Hollenberg, P.F., 2002. Mechanism-based inactivation of cytochrome P450 3A4 by 17-alpha-ethynylestradiol: evidence for heme destruction and covalent binding to protein. Journal of Pharmacology and Experimental Theraputics 301, 160-7. Cerca con Google

Lowry, O.H., Rosenbrough, N.Y., Farr, A.L., Randall, R.Y., 1951. Protein measurement with the Folin phenol reagent. Journal of Biological Chemistry 193, 265–275. Cerca con Google

Ma, Y.M., Ma, Z.Q., Gui, C.Q., Yao, J.S., Sun, R.Y., 2003. Hepatotoxicity and toxicokinetics of ketoconazole in rabbits. Acta Pharmacologica Sinica 24, 778-782. Cerca con Google

Maradonna, F., Polzonetti, V., Bandiera, S.M., Migliarini, B., Carnevali, O., 2004. Modulation of the hepatic CYP1A1 System in the Marine Fish Gobius niger, Exposed to Xenobiotic Compounds. Environmental science &Technology 38, 6277–6282. Cerca con Google

Marcomini A., V. Bonamin, S. Degetto and A. Giacometti (1999). Occurrence of organochlorine pollutants in three dated sediment cores from the lagoon of Venice. Organohaogenated Compounds, 43, 373-382. Cerca con Google

Machala, M., Soucˇek, P., Necˇa, J., Ulrich, R., Lamka, J., Szota´kova´, B., Ska´lova,´ 2003. Inter-species comparisons of hepatic cytochrome P450 enzyme levels in male ruminants. Archives of Toxicology 77, 555–560. Cerca con Google

McCune, J.S., Hawke, R.L., LeCluyse, E.L., Gillenwater, H.H., Hamilton, G., Ritchie, J., Lindley, C., 2000. In vivo and in vitro induction of human cytochrome P4503A4 by dexamethasone. Clinical Pharmacoogy and Therapeutic 68, 356–366. Cerca con Google

Merlanti, R., Gallina, G., Capolongo, F., Contiero, L., Biancotto, G., Dacasto, M., Montesissa, C., 2007. An in vitro study on metabolism of 17beta-boldenone and boldione using cattle liver and kidney subcellular fractions. Analitica Chimica Acta 586, 177-183. Cerca con Google

Miller, P.J., 1986. Gobiidae. In: Whitehead P.J.P., Buchot, M.L., Hureau, J.C., Nielsen, J., Tortonese, E. (eds.). Fishes of the North-eastern Atlantic and the Mediterranean. Vol. 3, UNESCO, Paris: 1019-1085 Cerca con Google

Miners, J.O., Smith, K.J., Robson, R.A., McManus, M.E., Veronese, M.E., Birkett, D.J., 1988. Tolbutamide hydroxylation by human liver microsomes. Biochemical Pharmacology 37, 1137-1144. Cerca con Google

Miners, J.O., Birkett, D.J., 1998. Cytochrome P4502C9: an enzyme of major importance in human drug metabolism. British Journal of Clinical Pharmacology 45, 525-538. Cerca con Google

Montesissa, C., Anfossi, P., van’t Klooster, G., Mengelers, M., 1996. The use of cultured hepatocytes from goats and cattle to investigate xenobiotic oxidative metabolism. Veterinary Research Communications 20, 449-460. Cerca con Google

Mugford CA, Kedderis GL., 1998. Sex-dependent metabolism of xenobiotics. Drug Metab Rev. 30, 441-498. Cerca con Google

Moslemi, S., Seralini, G.E., 1997. Inhibition and inactivation of equine aromatase by steroidal and non-steroid al compounds. A comparison with human aromatase inhibition. Journal of Enzyme Inhibition and Medicinal Chemistry 12, 241-254. Cerca con Google

Nakamura, A., Yamamoto, Y., Tasaki, T., Sugimoto, C., Masuda, M., Kazusaka, A., Fujita, S., 1995. Anti-peptide antibodies to the P4502D subfamily in rat, dog and man. Xenobiotica 25, 1103-1109. Cerca con Google

Nebbia, C., 2001. Biotransformation enzymes as determinants of xenobiotic toxicity in domestic animals. The Veterinary Journal 161, 238-252. Cerca con Google

Nebbia, C., Dacasto, M., Rossetto Giaccherino, A., Giuliano Albo, A., Carletti, M., 2003. Comparative expression of liver cytochrome P450-dependent monooxygenases in the horse and in other agricultural and laboratory species. The Veterinary Journal 165, 53–64. Cerca con Google

Nebbia, C., Dacasto, M., Carletti, M., 2004. Postnatal development of hepatic oxidative, hydrolytic and conjugative drug-metabolizing enzymes in female horses. Life Sciences 74, 1605-1619. Cerca con Google

Nebert, D.W., Roe, A.L., 2000. Ethnic and genetic differences in metabolism genes and risk of toxicity and cancer. The Science of the Total Environment 274, 93-102. Cerca con Google

Northrop, D.B., 1998. On the meaning of KM and V/K. Journal of Chemical Education 75, 1153-1157. Cerca con Google

Oesch-Bartlomowicz, B., Oesch, F., 2005. Phosphorylation of cytochromes P450: first discovery of a posttranslational modification of a drug-metabolizing enzyme. Biochemical and Biophysical Research and Communications 338, 446–449. Cerca con Google

Ogg, M.S., Williams, J.M., Tarbit, M., Goldfarb, P.S., Gray, T.J., Gibson, G.G., 1999, A reporter gene assay to assess the molecular mechanisms of xenobiotic-dependent induction of the human CYP3A4 gene in vitro. Xenobiotica 29, 269-279. Cerca con Google

Oikari, A., Nakari, T., 1982. Kraft pulp mill effluent components cause liver dysfunction in trout. Bulletin of Environmental Contamination and Toxicology 28, 226–270. Cerca con Google

Palamanda, J., Feng, W.W., Lin, C.C., Nomeir, A.A., 2000. Stimulation of tolbutamide hydroxylation by acetone and acetonitrile in human liver microsomes and in a cytochrome P-450 2C9-reconstituted system. Drug Metabolism and Disposition 28, 38–43. Cerca con Google

Pampori, N.A., Shapiro, B.H., 1993. Sexual dimorphism in avian hepatic monooxygenases. Biochemical Pharmacology 46, 885-890. Cerca con Google

Parkinson, A., 1996. Biotransformation of xenobiotics. In: C.D. Klaassen (Eds.), Casarett & Doull's Toxicology: The Basic Science Of Poisons. McGraw-Hill, New York, pp. 113-186. Cerca con Google

Pascussi, J.M, Drocourt, L., Fabre, J.M., Maurel, P., Vilarem, M.J., 2000a. Dexamethasone induces pregnane X receptor and retinoid X receptor-  expression in human hepatocytes: synergistic increase of CYP3A4 induction by pregnane X receptor activators. Molecular Pharmacology 58, 361-372. Cerca con Google

Pascussi, J.M, Gerbal-Chaloin, S., Fabre, J.M., Maurel, P., Vilarem, M.J., 2000b. Dexamethasone enhances constitutive androstane receptor expression in human hepatocytes: consequences on cytochrome P450 gene regulation. Molecular Pharmacology 58, 1441-1450. Cerca con Google

Pascussi, J.M., Gerbal-Chaloin, S., Drocourt, L., Maurel, P., Vilarem, M.J., 2003. The expression of CYP2B6, CYP2C9 and CYP3A4 genes: a tangle of networks of nuclear and steroid receptors. Biochim Biophys Acta 17, 243-53. Cerca con Google

Peffer, R.C, Moggs, J.G, Pastoor, T., Currie, R.A, Wright, J., Milburn, G., Waechter, F., Rusynm, I., 2007. Mouse liver effects of cyproconazole, a triazole fungicide: role of the constitutive androstane receptor. Toxicological Sciences 99, 315–325. Cerca con Google

Poels, C. L. M., Van Der Gaag, M. A., Van De Kerkhoff, J. F. J., 1980. An investigation into the long-term effects of Rhine water on rainbow trout. WaterResearch 14, 1029–1035. Cerca con Google

Pohl, R.J., Fouts, J.R., 1980. A rapid method for assaying the metabolism of 7-ethoxyresorufin by microsomal subcellular fractions. Analytical Biochemistry 107, 150-155. Cerca con Google

Poulos, T.L., 1991. Modeling of mammalian P450s on basis of P450cam X-ray structure. Methods in Enzymology 206, 11-30. Cerca con Google

Rahman, A., Korzekwa, K.R., Grogan, J., Gonzalez, F.J., Harris, J.W., 1994. Selective biotransformatijon of taxol to 6 alpha-hydroxytaxol by human cytrochrome P450 2C8. Cancer Research 54, 5543-5546. Cerca con Google

Ramsak, A., Stopar, K., Sepcic, K., Berden-Zrimec, M., Bajit, O., Malej, A., 2007. Reflection pf hydrocarbon pollution on hepatic EROD activity in the black goby (Gobius niger). Environmental Toxicology and Pharmacology 24, 304-310. Cerca con Google

Rendic, S., Nolteernsting, E., Schänzer, W., 1999. Metabolism of anabolic steroids by recombinant human cytochrome P450 enzymes. Gas chromatographic-mass spectrometric determination of metabolites. Journal of Chromatography B 735, 73-83. Cerca con Google

Ringel, M., Oesch, F., Gerl, M., Klebach, M., Quint, M., Bader, A., Böttger, T., Hengstler, J.G., 2001. Permissive and suppressive effects of dexamethasone on enzyme induction in hepatocyte co-coltures. Xenobiotica 32, 653-666. Cerca con Google

Reidy, G. F., Mehta, I., Murray, M., 1989. Inhibition of oxidative drug metabolism by orphenadrine: in vitro and in vivo evidence for isozymespecific complexation of cytochrome P-450 and inhibition kinetics. Molecular Pharmacology 35, 736–743. Cerca con Google

Roberts, E. S., Hopkins, Eddy, N., Foroozesh, M., Alworth, W. L., Halpert, J. R., Hollenberg, P. F., 1997. Inactivation of Cytochrome P450s 2B1, 2B4, 2B6, and 2B11 by Arylalkynes. Drug Metabolism and Disposition 25, 1242-1248. Cerca con Google

Roy, H.P., 2007. Pharmacogenetic Studies of Antidepressant Response: How Far from the Clinic? Psychiatric Clinics of North America 30, 125-138. Cerca con Google

Ryan, D.E., and Lewin, W., 1990. Purification and characterization of hepatic microsomal P-450. Pharmacoogy and Therapeutics 45, 153–239. Cerca con Google

Sallovitz, J., Lifschitz, A., Imperiale, F., Pis, A., Virkel, G., Lanusse, C., 2002. Breed differences on the plasma availability of moxidectin administered pour-on to calves. Veterinary Journal 164, 47–53. Cerca con Google

Schimmer, B.P., Parker, K.L., 2006. “Adrenocorticotropic hormone; adrenocortical steroids and their synthetic analogs; inhibitors of the synthesis and actions of adrenocortical hormones” in “Goodman & Gilman's the Pharmacological Basis of Therapeutics 11th Ed.” (editori: Brunton L., Lazo J., Parker K.L.) McGraw Hill, New York Cerca con Google

Schmelzer, E., Acikgoez, A., Frühauf, N.R., Crome, O., Klempnauer, J., Christians, U., Bader, A., 2006. Biotransformation of cyclosporin in primary rat, porcine and human liver cell co-cultures. Xenobiotica 36, 693-708. Cerca con Google

Schmidely, P., 1993. Quantitative bibliographic review on the use of anabolic hormones with steroidogenic action in ruminants for meat production. II. Principal mode of action. Reproduction Nutrition Developement 33, 297-323. Cerca con Google

Schwerin, M., Kuehn, C., Wimmers, S., Walz, C., Goldammer, T., 2006. Trait-associated expressed hepatic and intestine genes in cattle of different metabolic type: putative functional candidates for nutrient utilization. Journal of American Breeding and Genetics 123, 307–314. Cerca con Google

Sidhu, J.S., Omiecinski, C.J., 1995. cAMP-associated inhibition of phenobarbital-inducible cytochrome P450 gene expression in primary rat hepatocyte cultures. Journal of Biology 270, 12762-73. Cerca con Google

Silver, G, Reid, LM, Krauter, K.S., 1990. Dexamethasone-mediated regulation of 3-methylcholanthrene-induced cytochrome P-450d mRNA accumulation in primary rat hepatocyte cultures. The Journal of Biologica Chemistry 25, 3134-3138. Cerca con Google

Sinclair, P.A., Hancock, S. Gilmore, W.J., Squires, E.J., 2005. Metabolism of the 16-androstene steroids in primary cultured porcine hepatocytes. The Journal of Steroid Biochemistry and Molecular Biology 96, 79-87. Cerca con Google

Sivapathasundaram, S., Magnisali, P., Coldham, N.G., Howells, L.C., Sauer, M.J., Ioannides, C., 2001. A study of the expression of the xenobiotic-metabolizing cytochrome P450 proteins and of testosterone metabolism in bovine liver. Biochemical Pharmacology 62, 635-645. Cerca con Google

Sivapathasundaram S., Sauer M.J., Ioannides C., 2003. Xenobiotic conjugation system in deer compared with cattle and rat. Comparative Biochemistry and Physiology Part C: Toxicology and Pharmacology 134, 169–173. Cerca con Google

Sloof, W., van Kreijl, C.F., Baars, A.J., 1983. Relative liver weights and xenobiotic-metabolizing enzymes of fish from polluted surface waters in the Netherlands. Aquatic Toxicology 4, 1–14. Cerca con Google

Skaanild, M. T., e Friis, C., 2002. Is Cytochrome P450 CYP2D Activity Present in Pig Liver? Pharmacology & Toxicology 91, 198-203. Cerca con Google

Szotáková, B., Baliharová, V., Lamka, J., Nožinová, E., Wsól, V., VelíK, J., Machala, M., Nec, J., Soucek, P., Šusová, S., Skálová, L., 2004. Comparison of in vitro activities of biotransformation enzymes in pig, cattle, goat and sheep. Research in Veterinary Science 76, 43–51. Cerca con Google

Stabenfeldt, G.H., 2002. Attività riproduttiva della femmina. In: Swenson MJ, Reece WO, Duke’s Fisiologia degli Animali Domestici, Idelson-Gnocchi, Italia Cerca con Google

Tang, C., Shou, M., Rodrigues, D., 2000. Substrate-dependent effect of acetonitrile on human liver microsomal cytochrome P450 2C9 (CYP2C9) activity. Drug Metabolism and Disposition 28, 567-572. Cerca con Google

Timbrell, J.A., 1982. Principles of biochemical toxicology, Taylor and Francis, London. Cerca con Google

Tirona, R.G., Lee, W., Leake, B.F., Cline, C.B., Lamba, V., Parviz, F., Duncan, S.A., Inoue, Y., Gonzalez, F.J., Schuetz, E.G., Kim, R.B., 2003. The orphan nuclear receptor HNF4alpha determines PXR- and CAR-mediated xenobiotic induction of CYP3A4. Nature Medicine 9, 220-224. Cerca con Google

Tydèn, E., Olseèn, L., Tallkvist, J., Tjälve, H., Larsson, P., 2007. Cytochrome P4503A, NADPH cytochrome P450 reductase and cytochrome b5 in the upper airways in horse. Research in Veterinary Science 85, 80-85. Cerca con Google

Tsuchiya, Y., Nakajima, M., Yokoi ,T., 2005. Cytochrome P450-mediated metabolism of estrogens and its regulation in human. Cancer Letters 227, 115-124. Cerca con Google

Tsuchiya, Y., Nakajima, M., Takagi, S., Taniya, T., Yokoi, T., 2006. MicroRNA regulates the expression of human cytochrome P450 1B1. Cancer Research 66, 9090–9098. Cerca con Google

Van’t Klooster, G.A.E., Woutersen-van Nijnanten, F.M.A., Klein, W.R., Blaauboer, B.J., Noordhoek, J., van Miert, A.S.J.P.A.M., 1992. Effects of various medium formulations and attachment substrata on the performance of cultured ruminant hepatocytes in biotransformation studies. Xenobiotica 22, 523-534. Cerca con Google

Vegiopoulos, A., Herzig, S., 2007. Glucocorticoids, metabolism and metabolic diseases. Molecular and Cellular Endocrinology 275, 43-61. Cerca con Google

Velík, J., Baliharová, V., Skálova, L., Szotáková, B., Wsól, V., Lamka, J., 2003. Stereospecific biotransformation of albendazole in mouflon and rat-isolated hepatocytes. Journal of Veterinary Pharmacology and Therapeutics 26, 297-302. Cerca con Google

Vignier, V., Vandermeulen, J.H., Fraser, A.J., 1992. Growth and food conversion by Atlantic salmon parr during 40 days’ exposure to crude oil, Transactions of the American Fisheries Society 121, 322–332. Cerca con Google

Vincenti, M., Girolami, F., Capra, P., Pazzi, M., Carletti, m., Gardini, G., Nebbia, C., 2009. Study of dexamethasone urinary excretion profile in cattle by LC-MS/MS: comparison between therapeutic and growth promoting administration. Journal of Agriculture and Food Chemistry 57, 1299-1306. Cerca con Google

Walsky, R.L., Obach R.S., 2004. Validated assays for human cytochrome P450 activities. Drug Metabolism and Disposition 32, 647–660. Cerca con Google

Wang, R.W., Lu, A.Y.H., 1997. Inhibitory Anti-Peptide Antibody Against Human CYP3A4. Drug Metabolism and Disposition 25, 762-767 Cerca con Google

Waxman, D.J., Morrissey, J.J, Naik, S., Jauregui, H.O., 1990. Phenobarbital induction of cytochromes P-450. High-level long-term responsiveness of primary rat hepatocyte cultures to drug induction, and glucocorticoid dependence of the phenobarbital response. Biochemical Journal 271, 113-119. Cerca con Google

Weaver, R.J., Dickins, M., Burke D., 1995. Hydroxylation of the antimalarial drug 58C80 by CYP2C9 in human liver microsomes: comparison with mephenytoin and tolbutamide hydroxylations. Biochemical Pharmacology 49, 997–1004. Cerca con Google

Whyte, J.J., Jung, R.E., Schmitt, C.J., Tillit, D.E., 2000. Ethoxyresorufin-O-deethylase (EROD) activity in fish as a biomarker of chemical exposure. Critical Reviews in Toxicology 30, pp. 347–570. Cerca con Google

Williams, R.T., 1971. Biotransformation of xenobiotis: Phase I and Phase II Biotransformation. In: C.D. Klaassen (Eds.), Toxicology: The Basic Science Of Poisons. McGraw-Hill, New York, pp. 135-136. Cerca con Google

Williams, D.E., Lech, J.J. and Buhler, D.R., 1998. Xenobiotics and xenoestrogens in fish: modulation of cytochrome P450 and carcinogenesis. Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis 399, 179-192. Cerca con Google

Williams, E.T., Leyk, M., Wrighton, S.A., Davies, P.J.A., Loose, D.S., Shipley, G.L., Strobel, H.W., 2004. Estrogen regulation of the cytochrome P450 3A subfamily in humans. The Journal of Pharmacology and Experimental Therapeutics 31, 728-735. Cerca con Google

Williams, C.A., Lamprecht, E.D., 2008, Some commonly fed herbs and other functional foods in equine nutrition: a review. Vet J 178, 21-31. Cerca con Google

Witkamp, R., 1992. Oxidative drug metabolism in ruminants and laboratory species. (Tesi di dottorato), Utrecht. Cerca con Google

You, L., 2004. Steroid hormone biotransformation and xenobiotic induction of hepatic steroid metabolizing enzymes. Chemico-Biological Interaction 147, 233-246. Cerca con Google

Yuan, R., Madani, S., Wei, X., Reynolds, K., Huang, S., 2002. Evaluation of cytochrome P450 probe substrates commonly used by the pharmaceutical industry to study in vitro drug interactions. Drug Metabolism and Disposition 30, 1311–1319. Cerca con Google

Zancanella, V., Giantin, M., Lopparelli, R.M., Patarnello, T., Dacasto, M., Negrisolo, E. Proposed new nomenclature fo bos taurus cytochrome P450 involved in xenobiotic drug metabolism. Journal of veterinary Pharmacology and Therapeutics, doi: 10.1111/j.1365-2885.2010.0117.x Cerca con Google

Zeng, Z., Andrew, N.W., Arison, B.H., Luffer-Atlas, D., Wang, R.W., 1998. Identification of cytochrome P4503A4 as the major enzyme responsible for the metabolism of ivermectin by human liver microsomes. Xenobiotica 28, 313-321. Cerca con Google

Zhou, S., Koh, H.L., Gao, Y., Gong, Z.Y., Lee, E.J., 2004a. Herbal bioactivation: the good, the bad and the ugly. Life Sciences 74, 935-968. Cerca con Google

Zhou, S.F., Zhou, Z.W., Yang, L.P., Cai, J.P., 2009. Substrates, Inducers, Inhibitors and Structure-Activity Relationships of Human Cytochrome P450 2C9 and Implications in Drug Development. Curr Med Chem. Sep 1. [Epub ahead of print]. Cerca con Google

Zhu, B.T., Lee, A.J., 2005. NADPH-dependent metabolism of 17beta-estradiol and estrone to polar and nonpolar metabolites by human tissues and cytochrome P450 isoforms. Steroids 70, 225-244. Cerca con Google

Zweers-Zeilmaker, W.M., Horbach, G.J. and Witkamp, R.F., 1997. Differential inhibitory effects of phenytoin, diclofenac, phenylbutazone and a series of sulfonamides on hepatic cytochrome P4502C activity in vitro, and correlation with some molecular descriptors in the dwarf goat (Caprus hircus aegagrus). Xenobiotica 27, 769–780. Cerca con Google

Zweers-Zeilmaker, W.M., Horbach, G.J., Witkamp, R.F., 1998a. Effects of non steroidal anti-inflammatory drugs and sulfonamides on hepatic cytochrome P4502C activity in vitro in goats and cattle. Journal of Veterinary Pharmacology and Therapeutics 21, 154-157. Cerca con Google

Zweers-Zeimaker, W.M., Van Miert, A.S.J.P.A.M., Horbach, G.J., Witkamp, R.F., 1998b. In vitro complex formation and inhibition of hepatic cytochrome P450 activity by different macrolides and tiamulin in goats and cattle. Research in Veterinary Science, 66, 51–55. Cerca con Google

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