Title page for ETD etd-11212012-185014


Document Type Master's Dissertation
Author Mompati, Kefiloe Felicity
Email kefymompati@yahoo.com
URN etd-11212012-185014
Document Title The insensitivity of the crow (Corvusalbus) to diclofenac toxicity
Degree MSc
Department Paraclinical Sciences
Supervisor
Advisor Name Title
Prof V Naidoo Supervisor
Keywords
  • crow
  • Corvusalbus
  • species
  • diclofenac toxicity
Date 2012-09-07
Availability unrestricted
Abstract
Diclofenac has previously been shown to be toxic in three species of Gyps vultures (G. bengalensis, G. tenuirostris, and G. indicus) on the Indian subcontinent. Due to the devastating effect on the population of vultures (>99.9% species mortality), numerous efforts were initiated in order to protect the species. One such effort involved the removal of further threats to the species. At present the major threat identified has been the other non-steroidal drugs (NSAIDs) available for veterinary use. From research on ketoprofen and meloxicam (the former toxic and the latter safe), it was evident that toxicity was not general for the class of NSAIDs and that other factors played a role in toxicity. This unfortunately meant that each drug had to be tested individually in the vulture. While possible, the endangered status of vulture globally makes this approach unethical. As a result an alternate method of testing needed to be validated or sought. It was believed that a surrogate model could be the answer. The aim of this study was to establish if the crow could serve as such a surrogate model.

The toxic effect of diclofenac in crows (n=6) was evaluated in a two cross over studies at doses of 0.8 and 10 mg/kg. No signs of toxicity were evident during the period of clinical monitoring, or necropsy or clinical pathology. In addition the drug was barely detectable in the birds and was described by a half-life of elimination of approximately 2.5 hours. To better explain the absence of observable toxicity, a follow-up study was initiated using freshly harvested renal tubular epithelial (RTE) cells and hepatocytes in a cell culture assay previously validated for cytotoxicity and reactive-oxidative generation. In general, the in vitro study results showed the hepatocytes and RTE cells to be tolerant to the presence of diclofenac, with cell viability remaining in the region of 80%. In contrast meloxicam appeared to be more toxic as previously seen with chicken primary RTE cells. Based on the in vivo and in vitro culture results, it was speculated that the absence of toxicity in the crow was due to a combination of rapid half-life of metabolism in combination with low susceptibility of the cells to toxicity.

To further explain the role of metabolism in toxicity, meta-analysis of pharmacokinetic data for the domestic chicken (Gallus gallusGyps africanus), Cape Griffon (Gyps coprotheres) and Turkey vultures () were evaluated for trends in toxicity. The data clearly showed a trend toward toxicity when the half-life of elimination increased. It was therefore concluded that toxicity in Gyps species is probably related to zero-order metabolism, and therefore cannot be predicted by a surrogate model due to inter-species differences in metabolism. The crow is therefore not a surrogate model for toxicity testing in the place of the vulture.

Copyright 2011, University of Pretoria. All rights reserved. The copyright in this work vests in the University of Pretoria. No part of this work may be reproduced or transmitted in any form or by any means, without the prior written permission of the University of Pretoria

Please cite as follows:

Mompati, KF 2011, The insensitivity of the crow (Corvusalbus) to diclofenac toxicity, MSc dissertation, University of Pretoria, Pretoria, viewed yymmdd < http://upetd.up.ac.za/thesis/available/etd-11212012-185014 / >

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