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

Naidoo, Vinny; Swan, Gerry E.

doi:10.1016/j.cbpc.2008.07.014

Cited by 84 publications

(74 citation statements)

References 39 publications

(48 reference statements)

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“…Whilst the mechanism behind ketoprofen's toxicity in G. coprotheres is unknown, we have previously proposed that diclofenac toxicity is related to the ability of NSAIDs to interfere with uric acid transport at the cellular level (Naidoo and Swan 2009). It is plausible that ketoprofen toxicity occurs in the same way, i.e.…”

Section: Discussionmentioning

confidence: 99%

The toxicokinetics of ketoprofen in Gyps coprotheres: toxicity due to zero-order metabolism

Naidoo

Venter

Wolter³

et al. 2010

Arch Toxicol

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In a safety study, Cape GriVon vultures (Gyps coprotheres) were dosed with ketoprofen at single doses of »1 mg/kg (n = 5) and 5 mg/kg (n = 11). No toxicity was reported in the 1 mg/kg group, with the AUC inf , V z and Cl being 10.42 g/ml h, 0.37 l/kg and 0.10 l/h kg, respectively. Toxicity occurred in the 5 mg/kg group, with 7 of the 11 birds dying. Clinical signs of toxicity included depression, loss of appetite and apparent coma. Animals died within 48 h of dosing. The AUC inf , V z and Cl in the birds that survived were 52.26 g/ml h, 0.45 l/kg and 0.10 l/h kg, respectively. The AUC inf , V z and Cl in the birds those died were 207.90 g/ml h, 0.26 l/kg and 0.02 l/h kg, respectively. Based on the increase in the AUC inf and C max in the birds that died, we surmise that toxicity resulted from saturation of the metabolic process. While the exact metabolic pathway remains unknown in these vultures, we believe that toxicity may be due to pharmacogenomic diVerences in the cytochrome P450 pathway.

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Section: Discussionmentioning

confidence: 99%

The toxicokinetics of ketoprofen in Gyps coprotheres: toxicity due to zero-order metabolism

Naidoo

Venter

Wolter³

et al. 2010

Arch Toxicol

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“…Such factors are already covered in a recently published review article by Paital et al [29]. The authors made a perspective that hunting [31], pollution [30,[32][33][34], food scarcity and cannibalism [24,33,34], ingestion of contaminated food and food poisoning [35][36][37][38][39][40][41], multiple physiological disorders including nutritional problems [14,42], lack of proper nesting and resting places [8], genotoxic factors [43,44], problems related to breeding [24,45], electrocution and air traffic [38,46,47] epidemic and endemic diseases [38,[48][49][50][51], pathological susceptibility [22,41,48,[52][53][54] etc. may be contributing factors for vulture mortality.…”

Section: Other Reasons For Vulture Mortalitymentioning

confidence: 99%

“…Postmortem analyses of vulture carcasses from different locations have found traces of diclofenac and its derivative compounds in their tissues, while the biomagnification of the drug diclofenac in vultures is believed to be the sole cause of mass mortality of their population. Many authors states that diclofenac contributes to renal failure and hepatotoxicity, is the only cause of vulture population decline in India [11][12][13][14][15][16][17][18]28,34,[56][57][58][59][60]. However, the available reports are inadequate for arguing whether diclofenac is the only main cause of vulture mortality or whether, following diclofenac biomagnification, the increased susceptibility of vultures to microbial pathogens, diseases or physiological disorders, such as OS followed by metabolic depression, is responsible for their mortality in large scale [29].…”

Section: Biochemical Insightsmentioning

confidence: 99%

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Role of Cyclonic Storm as Natural Disaster and other Factors on Vulture Mortality in India

Paital¹

2016

J Geogr Nat Disast

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Post mortem analyses in vultures across India and its neighboring countries traced diclofenac and its derivative compounds in their carcasses. Therefore, it is inferred that biomagnification of diclofenac from the consumed infected domestic animal carcasses contributes mortality by causing renal failure and hepatic damages in vultures. However, reports also indicate that both extrinsic environmental and intrinsic cellular causes might also be contributing factors. It offers a debate to confirm whether only diclofenac is the primary cause of vulture mortality versus their susceptibility to microbial pathogens, diseases or physiological conditions, such as oxidative stress due to diclofenac biomagnification. It is observed that natural disasters such as heavy cyclonic storm which affect arboreal life may be one of the major causes of the death of vultures in some parts of India. Therefore, extrinsic insults such as heavy cyclonic storms are believed to be also contributing factor to affect arboreal life including vultures in some other parts of the world. A perspective is made on the above facts as a cause of catastrophic mortality of vultures in India.

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“…El uso de este fármaco en los países de Pakistán, Nepal e India entre 1990 y 2007 ha provocado la pérdida de aproximadamente el 97% de la población endémica de tres especies de buitres: buitre dorsiblanco bengalí (Gyps bangalensis), buitre hindú (Gyps indicus) y buitre picofino (Gyps tenuirostris), siendo clasificadas por la lista roja de las especies IUCN como en peligro crítico de extinción (Naidoo y Swan 2009;Taggart et al 2007;Anon 2015). Como consecuencia, los gobiernos de estos países prohibieron el uso veterinario de este fármaco en 2006(Anon 2015.…”

Section: Introductionunclassified

Diclofenaco en buitres: ¿podría provocar el declive de la población española?

Lindon

2017

Revista Complutense De Ciencias Veterinarias

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RESUMENEl diclofenaco es un potente antiinflamatorio utilizado en medicina veterinaria, responsable de la pérdida del 97% de las aves carroñeras del continente Asiático. La reciente autorización de comercialización en España de una especialidad farmacéutica que contiene este fármaco ha creado una preocupación, especialmente relevante, por ser este país la reserva de buitres de Europa. Con esta revisión pretendemos evaluar el riesgo que puede existir analizando el escenario español. El diclofenaco en aves provoca insuficiencia renal aguda por necrosis de las células del túbulo contorneado proximal impidiendo la excreción del ácido úrico, derivando en gota visceral grave y muerte. Los buitres son extremadamente sensibles ya que eliminan más lentamente ciertos fármacos y la dosis terapéutica recomendada en mamíferos es mortal en ellos. En Asia se dieron unas condiciones que favorecieron la grave problemática causada, tales como lascreencias religiosas, la formulación oral en bolo y el reducido coste de esta molécula.Palabras clave: diclofenaco, buitres, gota visceral, AINEs. ABSTRACTDiclofenac is a powerful anti-inflammatory that isused at veterinarian medicine. It is responsible for the 97% of the loss of the Carrion Birds of the Asian continent. Therecent

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

Abstract: Diclofenac (DF), a non-steroidal anti-inflammatory drug (NSAID),

Cited by 84 publications

References 39 publications

The toxicokinetics of ketoprofen in Gyps coprotheres: toxicity due to zero-order metabolism

The toxicokinetics of ketoprofen in Gyps coprotheres: toxicity due to zero-order metabolism

Role of Cyclonic Storm as Natural Disaster and other Factors on Vulture Mortality in India

Diclofenaco en buitres: ¿podría provocar el declive de la población española?

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