Diclofenac toxicity in Gyps vulture is associated with decreased uric acid excretion and not renal portal vasoconstriction

dc.contributor.authorNaidoo, Vinny
dc.contributor.authorSwan, Gerry E.
dc.date.accessioned2010-04-13T10:24:39Z
dc.date.available2010-04-13T10:24:39Z
dc.date.issued2009-04
dc.description.abstractDiclofenac (DF), a non-steroidal anti-inflammatory drug (NSAID), is largely regarded as one of the most devastating environmental toxicant in recent times, after accidental exposure via their food-chain lead to massive mortalities in three vulture species on the Asian subcontinent. Although the use of diclofenac was recently banned on the Indian subcontinent, following the favourable safety profile of meloxicam, its mechanism of toxicity remains unknown. In an attempt to establish this mechanism, we test three hypotheses using models established from either the domestic chicken (Gallus domesticus) or the African White-backed vulture (Gyps africanus). We demonstrate that both DF and meloxicam are toxic to renal tubular epithelial (RTE) cells following 12 h of exposure, due to an increase in production of reactive oxygen species (ROS), which could be temporarily ameliorated by pre-incubation with uric acid (UA). When cultures were incubated with either drug for only 2 h, meloxicam showed no toxicity in contrast to diclofenac. In both cases no increase in ROS production was evident. In addition, diclofenac decreased the transport of uric acid, by interfering with the p-amino-hippuric acid (PAH) channel. We conclude that vulture susceptibility to diclofenac results from a combination of an increased ROS, interference with UA transport and the duration of exposure.en
dc.description.sponsorshipRoyal Society for the Protection of Birds (RSPB). National Research Foundation of South Africa (NRF). Bayer Animal Health South Africa.en
dc.identifier.citationNaidoo, V & Swan, GE 2009, 'Diclofenac toxicity in Gyps vulture is associated with decreased uric acid excretion and not renal portal vasoconstriction', Comparative Biochemistry and Physiology Part C: Toxicology & Pharmacology, vol. 149, no. 3, pp. 269-274. [http://www.sciencedirect.com/science/journal/03009629]en
dc.identifier.issn1095-6433
dc.identifier.other10.1016/j.cbpc.2008.07.014
dc.identifier.other8621439700
dc.identifier.other7102127047
dc.identifier.otherI-7222-2013 
dc.identifier.otherA-1508-2008
dc.identifier.urihttp://hdl.handle.net/2263/13907
dc.language.isoenen
dc.publisherElsevieren
dc.rightsElsevieren
dc.subjectDiclofenacen
dc.subjectVultureen
dc.subjectMechanism of toxicityen
dc.subjectVulture crisisen
dc.subject.lcshToxicology -- South Africaen
dc.subject.lcshVeterinary toxicologyen
dc.subject.lcshPoisoning in animalsen
dc.titleDiclofenac toxicity in Gyps vulture is associated with decreased uric acid excretion and not renal portal vasoconstrictionen
dc.typePostprint Articleen

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