The Pied Crow (Corvus Albus) Is Insensitive to Diclofenac at Concentrations Present in Carrion

Abstract

ABSTRACT:Diclofenac, a nonsteroidal anti-inflammatory drug (NSAID), kills vultures (Gyps spp.) that consume tainted carcasses. As a result, vulture populations in India, Nepal, and Pakistan have been devastated. Studies on meloxicam and ketoprofen demonstrated that the toxicity of the NSAIDs is unpredictable, thereby necessitating individual testing of all available NSAIDs. Because it is no longer practical to use vultures for toxicity testing, we evaluated the Pied Crow (Corvus albus) as a model. Pied Crows (n56) were exposed to a dose of 0.8 and 10 mg/kg of diclofenac, with no signs of toxicity, and a rapid half-life of elimination. Using primary renal cell and hepatocyte cultures, a high tolerance was demonstrated at the cellular level. Meta-analysis of pharmacokinetic data for the Domestic Chicken (Gallus gallus) and the African White-backed (Gyps africanus), Cape Griffon (Gyps coprotheres), and Turkey Vultures (Cathartes aura) showed a trend toward toxicity when the half-life of elimination increased. We conclude that the crow is not susceptible to diclofenac and, more important, that toxicity in the Gyps species is probably related to zero-order metabolism.

Bioavailability and biochemical effects of diclofenac sodium 0.1% ophthalmic solution in the domestic chicken (Gallus gallus domesticus)

“…Previous studies demonstrated that sensitivity differences in response to NSAIDs exist between avian species . For example, one report determined that although chickens can succumb to diclofenac toxicity (50% lethal dose ~10 mg/kg), they are more tolerant of the biochemical effects (abnormal renal parameters and acute renal tubular necrosis) compared to Gyps vultures (50% lethal dose ~0.1 mg/kg) .…”

“…Biochemical or fatal changes of diclofenac‐treated birds in previous studies occurred at doses ranging from 0.005 mg/kg to 20 mg/kg with Gyps vultures being the most sensitive to effects . Of the studies that utilized chickens, a 2 mg/kg dose caused biochemical, but nonlethal, changes .…”

“…Multiple studies have evaluated the toxic effects of oral and injectable diclofenac in various avian species following a sharp decline in the population of Gyps vultures in South Asia after the scavenger birds ingested carrion from diclofenac‐treated livestock. These studies reported fatal renal disease and secondary visceral gout formation in the affected birds . Topical diclofenac sodium ophthalmic solution has been used in domestic and wild‐caught birds for treatment of ocular inflammation without reported negative clinical side effects .…”

Gota úrica visceral em coruja suindara (Tyto alba) de vida livre

“…Além das desordens metabólicas nutricionais e consequentes patologias renais sendo incriminadas como causas da gota úrica (Poffers et al 2002, Herbert et al 2011, o diclofenaco e derivados também tem sido incriminado como causador desta patologia, devido à contaminação ambiental por estes fármacos, levando a altos índices de mortalidade de rapinantes de vida livre (Muralidharan & Dhananjayan 2010, Naidoo et al 2011, Harris 2013, o que devemos estar atento, uma vez que estas drogas estão sendo amplamente utilizadas na medicina veterinária.…”

Comparative metabolism as a key driver of wildlife species sensitivity to human and veterinary pharmaceuticals

“…The choice of this species was twofold, firstly the easier availability to the study site, as well as being less endangered than the Indian vulture species. From this controlled acute toxicity study, the Cape Griffon vulture was shown to be equally susceptible to diclofenac as the oriental white-backed vulture at 0. , and a mean residence time of 15.11 + 4.13 h. To evaluate the importance of the pharmacokinetic profile obtained, Naidoo et al [61] compared it to those published for other bird species (figure 2). This included the African white-backed vulture (Gyps africanus), the pied crow (Corvus albus), the turkey vulture (Cathartes aura) and the domestic chicken (Gallus domesticus).…”