Effect of ivermectin on activities of cytochrome P450 isoenzymes in mouflon (Ovis musimon) and fallow deer (Dama dama)

Skálová, Lenka; Szotáková, Barbora; Machala, Miroslav; Neča, Jiřı́; Souček, Pavel; Havlasová, J; Wsól, Vladimı́r; Křı́dová, Lenka; Kvasničková, Eva; Lamka, J.

doi:10.1016/s0009-2797(01)00227-7

Cited by 31 publications

(27 citation statements)

References 17 publications

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“…In this study, a lack of a gender-effect was demonstrated in the in vitro liver drug metabolism of ivermectin, an antiparasitic macrocyclic lactone widely used in both veterinary and human medicine. This drug is known to be metabolised by CYP3A in man [61] whereas it might act either as a mild inducer of CYP3A in wild ruminants [53] or as a substrate of p-glycoprotein in the lamb [11]. Definitely more difficult to explain are the highest catalytic activities found in male PDM.…”

Section: Discussionmentioning

confidence: 99%

“…Based on our results and bibliographic evidence, no clear-cut conclusions can therefore be made. On a literature basis, it is known that among the most investigated constitutional factors are the species-differences in P450-dependent DME activities [35]; this is clearly evident for ruminants [10,30,46,51,53,55]. In the present study, no difference was noticed in P450 concentrations; by contrast, the amount of CYP3A apoprotein was significantly higher in OV as compared to cattle (CA); the order of magnitude was CA < GT < OV and these results confirm the presence of species-differences in the expression of some P450 isoforms and their lower expression, including CYP3A, in cattle vs. small ruminants [55,58].…”

Section: Discussionmentioning

confidence: 99%

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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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Section: Discussionmentioning

confidence: 99%

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 levels of 7-ethoxyresorufin (EROD), 7-methoxyresorufin (MROD), 7-pentoxyresorufin (PROD) O-dealkylases, and 7-benzyloxyresorufin O-dearylase (BROD) activity were determined at 37°C using fluorimetric determination of resorufin [9,51] 7-Penthoxyresorufin O-dealkylase PROD CYP2B [9,50] 7-Benzyloxyresorufin O-dearylase BROD CYP2B, CYP3A [9,50] 7-Methoxy-4-trifluoromethyl-coumarin demethylase MFCD CYP2C [13,40] 6-Chlorzoxazone hydroxylase CXOH CYP2E1, (CYP1A) [39,44] Thiobenzamide oxidase TBSO FMO [10] D,L-glyceraldehyde reductase GALR AKR1A [23] Metyrapone reductase METR (mic, cyt) 11b-HSD 1, AKR1C4, CBR [30] 4-Pyridine-carboxaldehyde reductase PCAR (mic, cyt) 3a-HSD, AKR1A, AKR1C [37] Daunorubicin reductase (pH 8.5) DAUR8 AKR1A [36] Daunorubicin reductase (pH 6.0) DAUR6 AKR1C2, CBR [16,36] Acenaphthenol dehydrogenase ANDH AKR1C1-4 [8,38] Oracin dehydrogenase ORDH (mic, cyt) 11b-HSD 1, AKR1C1-4, CBR [48,52] p-Nitrophenol-UGT UGT UGT [32] 1-Chloro-2,4-dinitrobenzene-GST GST GST [19] foxide, DMSO). Assays were performed using the Perkin-Elmer luminescence spectrophotometer LS 50B, with excitation and emission wavelengths of 530 nm and 585 nm, respectively.…”

Section: Enzyme Assaysmentioning

confidence: 99%

“…A chlorzoxazone hydroxylase (CXOH) assay was performed [39,44]. The final concentration of substrate (dissolved in 60 mM KOH) was 1 mM.…”

Section: Enzyme Assaysmentioning

confidence: 99%

Activities of biotransformation enzymes and flubendazole metabolism in lambs (Ovis aries): effect of gender and flubendazole therapy

Bártíková

Křížová

Štěpničková

et al. 2010

Pharmacological Reports

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Abstract:The effect of flubendazole (FLU) therapy on in vitro FLU biotransformation and the activities of selected biotransformation enzymes were investigated in male and female lambs. Four experimental groups were used: control (untreated) ewes and rams and FLU-treated ewes and rams (orally, 15 mg/kg per day, for three consecutive days). Subcellular fractions were prepared from liver and intestinal mucosa 24 h after the final dosage was administered. Activities of cytochromes P450 (CYP), flavine monooxygenases (FMO), carbonyl reducing enzymes, UDP-glucuronosyl transferase (UGT) and glutathione S-transferase were tested. Significant gender differences were observed for FMO-mediated activity (2-fold higher in ram lambs) and UGT activity (up to 30% higher in ewe lambs), but no gender differences were observed in FLU metabolism. FLU-treatment of lambs moderately changed the activities of some CYPs, FMO, and UGT in liver microsomes. In vitro FLU reduction was not altered in the liver, but was slightly higher in the small intestine of FLU pre-treated lambs. This correlated with the higher carbonyl reductase activities measured in the gut mucosa of these animals.

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“…6β-testosterone hydroxylase activity (6β-TOH) was assayed using the method described by Reinerinck et al (1991) with slight modifications (Skalova et al, 2001). The final concentration of substrate (dissolved in methanol) was 250µM and the amount of microsomal protein was 0.6-0.8 mg.…”

Section: Enzyme Assaysmentioning

confidence: 99%

A single adulticide dose of albendazole induces cytochromes P4501A in mouflon (Ovis musimon) with dicrocoeliosis

Lamka¹,

Křížová²,

Cvilink³

et al. 2007

Vet. Med. - Czech

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Contact handling with wild or semi-domesticated animals requires limiting animal stress to minimum. In this respect, single administration of drug should be preferred in contact therapy of mouflon (Ovis musimon) infected by lancet fluke (Dicrocoelium dendriticum). We tested single administration of albendazole (ABZ) (30 mg/kg of body weight) in a form of oral suspension and investigated to reach anthelmintic effects and to modulate biotransformation enzymes in liver and small intestine. Two weeks after ABZ administration coprology and necropsy findings document the adulticide effect in liver. The activities of eight biotransformation enzymes and ABZ biotransformation were tested in hepatic and intestinal subcellular fractions from control and ABZ treated animals. The highest inductive effect of ABZ was detected on cytochromes P4501A (CYP1A) activities. Increased amount of CYP1A proteins was confirmed using western blotting. In hepatic and intestinal microsomes, velocity of albendazole sulfoxide (ABZSO) formation was unaffected, but a shift in ratio of individual ABZSO enantiomers was observed. The second step of ABZ biotransformation corresponding to the formation of the pharmacologically inactive albendazole sulfone, was significantly accelerated both in liver and intestine of ABZ treated animals. The increase of ABZ deactivation could facilitate the development of anthelmintic resistance in parasites. Although single ABZ dose is therapeutically effective, its potential to induce CYP1A should be taken in account for controling helmithoses.

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Effect of ivermectin on activities of cytochrome P450 isoenzymes in mouflon (Ovis musimon) and fallow deer (Dama dama)

Cited by 31 publications

References 17 publications

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

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

Activities of biotransformation enzymes and flubendazole metabolism in lambs (Ovis aries): effect of gender and flubendazole therapy

A single adulticide dose of albendazole induces cytochromes P4501A in mouflon (Ovis musimon) with dicrocoeliosis

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