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Effect of cytochrome P450 inhibition on toxicity of diclofenac in chickens: Unravelling toxicity in Gyps vultures
2022
Locke,Sara | Naidoo,Vinny | Hassan,Ibrahim | Duncan,Neil
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.
Show more [+] Less [-]Acaricidal activity of the aqueous and hydroethanolic extracts of 15 South African plants against Rhipicephalus turanicus and their toxicity on human liver and kidney cells
2019
Fouche, Gerda(University of Pretoria Faculty of Natural and Agricultural Sciences Chemistry Department) | Adenubi, Olubukola T.(University of Pretoria Department of Paraclinical Sciences) | Leboho, Tlabo(Council for Scientific and Industrial Research (CSIR) Biosciences) | McGaw, Lyndy J.(University of Pretoria Department of Paraclinical Sciences) | Naidoo, Vinny(University of Pretoria Faculty Veterinary Science Biomedical Research Centre) | Wellington, Kevin W.(Council for Scientific and Industrial Research (CSIR) Biosciences) | Eloff, Jacobus N.(University of Pretoria Department of Paraclinical Sciences)
Hot water and hydroethanolic (70:30) extracts were prepared from 15 plant species, which were investigated to discover eco-friendly and less expensive tick control methods as an alternative to synthetic acaricides. A contact bioassay was used to determine the acaricidal activity of these extracts against the cattle tick, Rhipicephalus turanicus (Acari: Ixodidae) at a concentration of 20% (200 mg/mL). The hydroethanolic extracts had better activity than the hot water extracts against R. turanicus. The hydroethanolic extract from Tabernaemontana elegans (leaves) had the best mortality (87.0%). This was followed by Calpurnia aurea (stems) with a mortality of 75.0%, Schkuhria pinnata (whole plant) with a mortality of 67.0% and Aloe rupestris (leaves) with a mortality of 66.6%. The toxicity of the plant extracts was also investigated and it was found that most of the hydroethanolic and hot water extracts were either safe or very safe on human Vero kidney and liver HepG2 cells. From this study, it was evident that botanicals have the potential to be developed as environmentally benign natural acaricides against R. turanicus.
Show more [+] Less [-]First report of field outbreaks of ergot-alkaloid toxicity in South Africa
1996
Schneider, D.J. (Regional Veterinary Laboratory, Stellenbosch (South Africa)) | Miles, C.O. | Garthwaite, I. | Van Halderen, A. | Wessels, J.C. | Lategan, H.J.
Teratogenicity of a mutagenised Rift Valley fever virus (MVP 12) in sheep
2002
Hunter, P. (Onderstepoort Biological Products Ltd. (South Africa)) | Erasmus, B.J. | Vorster, J.H.
Putative avocado toxicity in two dogs
1994
Buoro, I.B.J. | Nyamwange, S.B. | Munyua, S.M. (Nairobi Univ. (Kenya)) | Chai, D.