Effect of oral administration of low doses of pentobarbital on the induction of cytochrome P450 isoforms and cytochrome P450-mediated reactions in immature Beagles

Kawalek, Joseph C.; Howard, Karyn D.; Farrell, Dorothy E.; Derr, Janice; Cope, Carol V.; Jackson, J.; Myers, Michael J.

doi:10.2460/ajvr.2003.64.1167

Cited by 5 publications

(6 citation statements)

References 23 publications

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“…Furthermore, the barbiturate provoked an explicit and significant increase in the in vitro metabolism of the chosen CYP2B22-dependent substrates; i.e., benzphetamine [ 10 , 100 , 102 ], benzyloxyresorufin [ 10 , 94 , 96 , 101 ], and 7-EFMC [ 94 ]. Some of the present results corroborated those previously observed in other veterinary species treated with PB, such as sheep [ 33 ], beagle dog [ 39 , 111 ], pig [ 30 ], and rabbit [ 34 ]. However, PB (100 μM) did not induce the CYP2B-depedent O -demethylation of 7-EFMC in horse primary hepatocytes [ 40 ].…”

Section: Discussionsupporting

confidence: 91%

“…Phenobarbital significantly increased the in vitro metabolism ( N- demethylation) of the abovementioned substrates, and especially of 7-MFMC. These results were quite clear, and at least partly confirmed those obtained in canines [ 111 ] and pigs [ 30 ]; nevertheless, they should be considered with caution, in light of the shortcomings in bovine CYP2C expression, regulation, and substrate specificity mentioned above.…”

Section: Discussionsupporting

confidence: 82%

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Induction by Phenobarbital of Phase I and II Xenobiotic-Metabolizing Enzymes in Bovine Liver: An Overall Catalytic and Immunochemical Characterization

Cantiello

Carletti

Giantin

et al. 2022

IJMS

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In cattle, phenobarbital (PB) upregulates target drug-metabolizing enzyme (DME) mRNA levels. However, few data about PB’s post-transcriptional effects are actually available. This work provides the first, and an almost complete, characterization of PB-dependent changes in DME catalytic activities in bovine liver using common probe substrates and confirmatory immunoblotting investigations. As expected, PB increased the total cytochrome P450 (CYP) content and the extent of metyrapone binding; moreover, an augmentation of protein amounts and related enzyme activities was observed for known PB targets such as CYP2B, 2C, and 3A, but also CYP2E1. However, contradictory results were obtained for CYP1A, while a decreased catalytic activity was observed for flavin-containing monooxygenases 1 and 3. The barbiturate had no effect on the chosen hydrolytic and conjugative DMEs. For the first time, we also measured the 26S proteasome activity, and the increase observed in PB-treated cattle would suggest this post-translational event might contribute to cattle DME regulation. Overall, this study increased the knowledge of cattle hepatic drug metabolism, and further confirmed the presence of species differences in DME expression and activity between cattle, humans, and rodents. This reinforced the need for an extensive characterization and understanding of comparative molecular mechanisms involved in expression, regulation, and function of DMEs.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionsupporting

confidence: 82%

Induction by Phenobarbital of Phase I and II Xenobiotic-Metabolizing Enzymes in Bovine Liver: An Overall Catalytic and Immunochemical Characterization

Cantiello

Carletti

Giantin

et al. 2022

IJMS

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“…by using primary hepatocytes, liver slices or established cell lines), in laboratory species (e.g. Jones et al ., ; Zheng et al ., ) and, seldom, in the dog (Kawalek et al ., ; Fukunaga et al ., ). On the contrary, a single‐dose protocol was used in those in vivo studies where the effects of PB were investigated in veterinary species (Dupuy et al ., ; Chirulli et al ., ; Goryia et al ., ; Marini et al ., ).…”

Section: Discussionmentioning

confidence: 98%

“…Thus, PB was (Dupuy et al ., ) and it is still used as a prototypical inducer useful to characterize DMEs expression (Longo et al ., ), NR‐dependant regulation phenomena (Tamasi et al ., ), as well as potential drug–drug interactions (Ballent et al ., ). By contrast, few papers investigating the in vivo effects of PB upon DMEs gene expression in veterinary species have been published so far and none in cattle (Kawalek et al ., ; Chirulli et al ., ; Goryia et al ., ; Marini et al ., ; Makino et al ., ).…”

Section: Discussionmentioning

confidence: 98%

Tissue distribution and phenobarbital induction of target SLC‐ and ABC‐ transporters in cattle

Zancanella

Giantin

Lopparelli

et al. 2012

Vet Pharm & Therapeutics

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In veterinary pharmaco-toxicological sciences, few data about uptake and efflux drug transporters (DTs) expression and regulation phenomena have been published. In this study, the tissue distribution and transcriptional modulation of solute carrier (SLC) and ATP-binding cassette (ABC) DTs were investigated in cattle orally administered with phenobarbital (PB) by using a quantitative real-time RT-PCR approach. The criterion for target gene selection was the PB-responsiveness in human and rodent model species. All target DTs were expressed in the liver. Only two of the seven PB-responsive target DTs (SLCO1B3 and SLC10A1) were not constitutively expressed in cattle extra-hepatic tissues. The greatest number of DTs (SLCO2B1, ABCB1, ABCC2, ABCG2) were expressed in intestine and testis, followed by, adrenal gland (SLCO2B1, ABCB1, ABCG2), lung (ABCB1, ABCG2), kidney, and skeletal muscle (ABCG2). PB administration never altered DTs mRNA levels, except for an increase in hepatic ABCC2 mRNA and a down-regulation of renal ABCG2. Altogether, these results confirm only to some extent data obtained in humans and laboratory species; clearly, they should be considered a preliminary step for further molecular investigations about species-differences in DT gene expression and regulation as well as in DT expression and function.

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“…As shown in Table 1 several drugs have been demonstrated to induce various CYPs and UDP-glucuronosyltransferase in humans. Among them, phenobarbital has been found to induce some CYPs in dogs [17–20] . The drug induces enzyme through activating CAR.…”

Section: Enzyme Inductionmentioning

confidence: 99%

Possible drug–drug interaction in dogs and cats resulted from alteration in drug metabolism: A mini review

Sasaki

Shimoda

2015

Journal of Advanced Research

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Effect of oral administration of low doses of pentobarbital on the induction of cytochrome P450 isoforms and cytochrome P450-mediated reactions in immature Beagles

Abstract: Several CYP isoforms and their associated reactions were induced in dogs by oral administration of low amounts of pentobarbital.

Cited by 5 publications

References 23 publications

Induction by Phenobarbital of Phase I and II Xenobiotic-Metabolizing Enzymes in Bovine Liver: An Overall Catalytic and Immunochemical Characterization

Induction by Phenobarbital of Phase I and II Xenobiotic-Metabolizing Enzymes in Bovine Liver: An Overall Catalytic and Immunochemical Characterization

Tissue distribution and phenobarbital induction of target SLC‐ and ABC‐ transporters in cattle

Possible drug–drug interaction in dogs and cats resulted from alteration in drug metabolism: A mini review

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