Effect of cytochrome P450 inhibition on toxicity of diclofenac in chickens: Unravelling toxicity in Gyps vultures

Onderstepoort Journal of Veterinary Research

Field Value
Title Effect of cytochrome P450 inhibition on toxicity of diclofenac in chickens: Unravelling toxicity in Gyps vultures
Creator Locke, Sara Naidoo, Vinny Hassan, Ibrahim Duncan, Neil
Subject Veterinary; pharmacology; toxicology diclofenac; toxicity; vulture; cytochrome P450; pharmacokinetics; chicken
Description Diclofenac was responsible for the decimation of Gyps vulture species on the Indian subcontinent during the 1980s and 1990s. Gyps vultures are extremely sensitive (the lethal dose 50 [LD50] ~ 0.1 mg/kg – 0.2 mg/kg), with toxicity appearing to be linked to metabolic deficiency, demonstrated by the long T1/2 (~12 h – 17 h). This is in striking comparison to the domestic chicken (Gallus gallus domesticus), in which the LD50 is ~10 mg/kg and the T1/2 is ~1 h. The phase 1 cytochrome P450 (CYP) 2C subfamily has been cited as a possible reason for metabolic deficiency. The aim of this study was to determine if CYP2C9 homolog pharmacogenomic differences amongst avian species is driving diclofenac toxicity in Gyps vultures. We exposed each of 10 CYP-inhibited test group chickens to a unique dose of diclofenac (as per the Organisation for Economic Co-operation and Development [OECD] toxicity testing guidelines) and compared the toxicity and pharmacokinetic results to control group birds that received no CYP inhibitor. Although no differences were noted in the LD50 values for each group (11.92 mg/kg in the CYP-inhibited test group and 11.58 mg/kg in the control group), the pharmacokinetic profile of the test group was suggestive of partial inhibition of CYP metabolism. Evaluation of the metabolite peaks produced also suggested partial metabolic inhibition in test group birds, as they produced lower amounts of metabolites for one of the three peaks demonstrated and had higher diclofenac exposure. This pilot study supports the hypothesis that CYP metabolism is varied amongst bird species and may explain the higher resilience to diclofenac in the chicken versus vultures.
Publisher AOSIS
Contributor University of Pretoria
Date 2022-06-14
Type info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion — Experimental
Format text/html application/epub+zip text/xml application/pdf
Identifier 10.4102/ojvr.v89i1.1978
Source Onderstepoort Journal of Veterinary Research; Vol 89, No 1 (2022); 8 pages 2219-0635 0030-2465
Language eng
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https://ojvr.org/index.php/ojvr/article/view/1978/2356 https://ojvr.org/index.php/ojvr/article/view/1978/2357 https://ojvr.org/index.php/ojvr/article/view/1978/2358 https://ojvr.org/index.php/ojvr/article/view/1978/2359
Coverage — — Domestic chicken; 5 weeks; mixed sex
Rights Copyright (c) 2022 Sara Locke, Vinny Naidoo, Ibrahim Hassan, Neil Duncan https://creativecommons.org/licenses/by/4.0