Comparison of in vitro activities of biotransformation enzymes in pig, cattle, goat and sheep

Szotáková, Barbora; Baliharová,; Lamka, J.; Nozinová, E; Wsól, Vladimı́r; Velík, J.; Machala, Miroslav; J, Neca; Souček, Pavel; Šůsová, Simona; Skálová, Lenka

doi:10.1016/s0034-5288(03)00143-7

Cited by 91 publications

(93 citation statements)

References 26 publications

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“…In contrast, Monshouwer et al (1998) and Anzenbacher et al (1998) could not detect PROD activity in cultured pig hepatocytes and minipig liver microsomes, respectively. The possible reasons for those disagreements between different studies are discussed elsewhere (Szotá ková et al, 2004). Activities of COH and PNPH in the present study were approximately within the activity range reported earlier (Zamaratskaia et al, 2006).…”

Section: Discussionsupporting

confidence: 73%

“…First, general knowledge about the effects of industrial pollutants and pharmacologically active substances is important in veterinary science (Szotá ková et al, 2004). Second, CYP450 in food-producing animals, including pigs, are crucial in the regulation of the amounts of drugs and other chemicals in animal tissues and possibly food products for human consumption and animal feeding stuffs.…”

Section: Introductionmentioning

confidence: 99%

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Modulation of porcine cytochrome P450 enzyme activities by surgical castration and immunocastration

Zamaratskaia

Žlábek

Chen

et al. 2009

Animal

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The present study aimed to evaluate some cytochrome P450 metabolic enzyme activities in hepatic microsomes prepared from entire male pigs (uncastrated pigs), surgically castrated pigs and pigs immunized against gonadotropin-releasing hormone (immunocastrated pigs). The activities of the following enzymes were measured: ethoxyresorufin O-deethylase (EROD, CYP1A1/ 1A2), methoxyresorufin O-deethylase (MROD, CYP1A2), pentoxyresorufin O-depentylase (PROD, CYP2B), coumarin hydroxylase (COH, CYP2A) and p-nitrophenol hydroxylase (PNPH, CYP2A/2E1). The total cytochrome P450 contents were not affected by either surgical or immunocastration. Hepatic microsomal activities for EROD, PROD, COH and PNPH were lower in entire male pigs compared with surgically castrated and immunocastrated pigs ( P , 0.05). Surgically and immunocastrated male pigs were similar with respect to EROD, MROD, PROD and COH activities ( P . 0.05), whereas surgically castrated pigs exhibited lower PNPH activity compared with immunocastrated pigs ( P 5 0.029). The effect of different concentrations of testicular steroidstestosterone, 17b-estradiol, free estrone and androstenone -on enzyme activities was evaluated by in vitro microsomal study. Testosterone at the concentration of 8 pmol/ml inhibited EROD activities and estradiol-17b at the concentration of 1.8 pmol/ml inhibited PROD activities in hepatic microsomes from surgically castrated pigs. The highest concentration of androstenone (7520 pmol/ml) inhibited COH activities, whereas a 42-fold lower concentration of androstenone (180 pmol/ml) stimulated COH activities in surgically castrated pigs. Both free estrone (3.5 pmol/ml) and androstenone (55 pmol/ml) inhibited EROD activities in microsomes from entire male pigs. Stimulation of COH activities by the highest dose of free estrone (18 pmol/ml) was recorded in microsomes from entire male pigs. However, these effects of steroids were not concentration-dependent and the maximum extent did not exceed 615% variation compared with the controls. There was no inhibition of PNPH activities in the hepatic microsomes from either entire or castrated pigs. In conclusion, we showed that EROD, PROD, COH and PNPH activities were lower in entire male pigs compared with those in surgically and immunocastrated pigs. Direct inhibition by the testicular steroids -testosterone, 17b-estradiol, free estrone and androstenone -was not the primary cause of the reduced enzyme activities.Keywords: castration, cytochrome P450, porcine liver microsomes, steroids ImplicationsThe present study evaluated some cytochrome P450 enzyme activities in liver microsomes from uncastrated male pigs, surgically castrated pigs and pigs immunized against gonadotropin-releasing hormone (immunocastrated pigs). We found that CYP1A1, CYP2A, CYP2B and CYP2E1 activities were lower in uncastrated male pigs compared with surgically castrated and immunocastrated pigs. These findings strengthen the hypothesis of testicular steroid involvement in cytochrome P450 enzyme regulation. The differences in the ac...

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Section: Discussionsupporting

confidence: 73%

Section: Introductionmentioning

confidence: 99%

Modulation of porcine cytochrome P450 enzyme activities by surgical castration and immunocastration

Zamaratskaia

Žlábek

Chen

et al. 2009

Animal

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“…It has been shown that there are significant species variations regarding the elimination kinetics of several drugs (Shukla et al, 2007). Szotakova et al, (2004) have demonstrated marked differences in the in vitro activities of biotransformation enzymes among animal species. Plasma from human, mouse, porcine and rat was used in these studies in order to evaluate the in vitro stability of the HDACIs.…”

Section: Discussionmentioning

confidence: 99%

In vitro plasma stability, permeability and solubility of mercaptoacetamide histone deacetylase inhibitors

Konsoula

Jung

2008

International Journal of Pharmaceutics

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Histone deacetylase inhibitors (HDACIs) are emerging as a new class of therapeutic agents with potent antitumor activities in a broad spectrum of human cancers. In this study, the in vitro plasma stability, permeability, solubility, and lipophilicity (logD) of two mercaptoacetamide-based HDACIs (coded as W2 and S2) were evaluated and compared to Vorinostat (SAHA). The results demonstrated that the compounds manifested high solubility in HCl (pH 1.2) but lower in PBS (pH 7.4) than SAHA. Moreover, mercaptoacetamide-based HDACIs exhibited higher lipophilicity values compared to SAHA. The permeability of these compounds was evaluated using the Caco-2 cell monolayer as a model of the intestinal mucosa. The Caco-2 studies revealed that the compounds S2 and W2 are highly permeable with apparent permeability coefficients (P app ) in the apical to basolateral direction of 7.33 × 10 −6 and 15.0 × 10 −6 cm/s, respectively. The in vitro stability was determined in human, mouse, porcine and rat plasma. Data showed that the compound W2 is more stable in human and rat plasma and the S2 is more stable in all plasma species than SAHA. Taken together, these results indicate that the mercaptoacetamide-based HDACIs possess favorable solubility, lipophilicity, permeability and plasma stability features.

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“…Many studies have mapped out the molecular biology of this superfamily and nowadays it can be divided into many subfamilies, each of which (particularly those belonging to numbers 1 to 4) is linked to a different set of drugs [33,56]; moreover, numerous investigators have identified the substrate specificities of each single isoform [33]. Recently, some studies which report the metabolism of substrates as models for specific enzymatic pathways in liver preparations of farm animals have been published too [29,37,49,55].…”

Section: Discussionmentioning

confidence: 99%

Effect of breed and gender on bovine liver cytochrome P450 3A (CYP3A) expression and inter-species comparison with other domestic ruminants

et al. 2005

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-The cytochrome P450 (P450) superfamily represents a group of relevant enzymes in the field of drug metabolism and several exogenous or constitutional factors contribute to regulate its expression. Cattle represent an important source of animal-derived food-products and studies concerning the P450 expression are needed for the extrapolation of pharmacotoxicological data from one species to another and for the evaluation of the consumer's risk associated with the consumption of harmful residues found in foodstuffs. In the present study, possible breed-, genderand species-differences in P4503A (the P450 subfamily more expressed in the human liver) expression were studied in vitro in Piedmontese (PDM) and Limousin (LIM) meat cattle breeds of both sexes and in domestic Ruminants (cattle, sheep and goats). Cytochrome P450 and P4503A contents as well as CYP3A-dependent drug metabolising enzymes (DME) were measured in liver microsomes. Significant lower levels of P450 (P < 0.001) and P4503A (P < 0.05) contents were observed in PDM vs. LIM of both sexes; the P4503A-dependent DME activities were significantly (P values ranging from 0.05 up to 0.001) higher in PDM cattle, particularly in males. A gendereffect in DME activities was noticed (P < 0.05) only in PDM male cattle. With regards to the species, the expression of both P4503A apoprotein and some of the related DME activities were more pronounced in sheep (P < 0.01 vs. cattle) and in goats (P < 0.05 vs. sheep; P < 0.01 vs. cattle) than in cattle. The significant differences in P4503A expression observed in LIM and PDM cattle are consistent with previously published data on strain-and breed-differences pointed out in rats and men. As far as a possible sex-effect is concerned, no clear-cut evidence is likely to be drawn. Finally, P4503A expression was more relevant in small ruminants. ruminants / liver drug metabolism / CYP3A / gender / breed

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Comparison of in vitro activities of biotransformation enzymes in pig, cattle, goat and sheep

Cited by 91 publications

References 26 publications

Modulation of porcine cytochrome P450 enzyme activities by surgical castration and immunocastration

Modulation of porcine cytochrome P450 enzyme activities by surgical castration and immunocastration

In vitro plasma stability, permeability and solubility of mercaptoacetamide histone deacetylase inhibitors

Effect of breed and gender on bovine liver cytochrome P450 3A (CYP3A) expression and inter-species comparison with other domestic ruminants

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