Oxidative stress has been implicated to play a role, at least in part, in pathogenesis of many disease conditions and toxicities in animals. Overproduction of reactive oxygen species and free radicals beyond the cells intrinsic capacity to neutralize following xenobiotics exposure leads to a state of oxidative stress and resultant damages of lipids, protein, and DNA. Lead and cadmium are the common environmental heavy metal pollutants and have widespread distribution. Both natural and anthropogenic sources including mining, smelting, and other industrial processes are responsible for human and animal exposure. These pollutants, many a times, are copollutants leading to concurrent exposure to living beings and resultant synergistic deleterious health effects. Several mechanisms have been explained for the damaging effects on the body system. Of late, oxidative stress has been implicated in the pathogenesis of the lead- and cadmium-induced pathotoxicity. Several ameliorative measures to counteract the oxidative damage to the body system aftermath or during exposure to these toxicants have been assessed with the use of antioxidants. The present review focuses on mechanism of lead- and cadmium-induced oxidate damages and the ameliorative measures to counteract the oxidative damage and pathotoxicity with the use of supplemented antioxidants for their beneficial effects.

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Veterinary use of the nonsteroidal anti-inflammatory (NSAID) drug diclofenac in South Asia has resulted in the collapse of populations of three vulture species of the genusGyps to the most severe category of global extinction risk. Vultures are exposed to diclofenac when scavenging on livestock treated with the drug shortly before death. Diclofenac causes kidney damage, increased serum uric acid concentrations, visceral gout, and death. Concern about this issue led the Indian Government to announce its intention to ban the veterinary use of diclofenac by September 2005. Implementation of a ban is still in progress late in 2005, and to facilitate this we sought potential alternative NSAIDs by obtaining information from captive bird collections worldwide. We found that the NSAID meloxicam had been administered to 35 captiveGyps vultures with no apparent ill effects. We then undertook a phased programme of safety testing of meloxicam on the African white-backed vultureGyps africanus, which we had previously established to be as susceptible to diclofenac poisoning as the endangered AsianGyps vultures. We estimated the likely maximum level of exposure (MLE) of wild vultures and dosed birds by gavage (oral administration) with increasing quantities of the drug until the likely MLE was exceeded in a sample of 40G. africanus. Subsequently, sixG. africanus were fed tissues from cattle which had been treated with a higher than standard veterinary course of meloxicam prior to death. In the final phase, ten Asian vultures of two of the endangered species(Gyps bengalensis,Gyps indicus) were dosed with meloxicam by gavage; five of them at more than the likely MLE dosage. All meloxicam-treated birds survived all treatments, and none suffered any obvious clinical effects. Serum uric acid concentrations remained within the normal limits throughout, and were significantly lower than those from birds treated with diclofenac in other studies. We conclude that meloxicam is of low toxicity toGyps vultures and that its use in place of diclofenac would reduce vulture mortality substantially in the Indian subcontinent. Meloxicam is already available for veterinary use in India.

Widespread veterinary use of the non-steroidal anti-inflammatory drug diclofenac is responsible for the population collapse of three species of Gyps vulture in south Asia; these species are now critically endangered. Vultures die when they consume carcasses of livestock that contain lethal residues of diclofenac. National and international conservation organizations have urgently recommended that diclofenac be banned and replaced with alternative drugs that are relatively safe to Gyps vultures and other scavenging birds. We tested the safety of the NSAID meloxicam on the oriental white-backed vulture, long-billed vulture and a range of other scavenging birds in India (Egyptian vulture Neophron percnopterus, cattle egret Bubulcus ibis, house crow Corvus splendens, large-billed crow Corvus machrorhynchos and common mynah Acridotheres tristis). Meloxicam was administered by oral intubation [at 0.5 and 2.0 mg kg À1 vulture body weight (bw)], or through feeding with muscle or liver tissue (at 0.3 to 2.1 mg kg À1 vulture bw) from meloxicam-treated buffalo Bubalus bubalis. We estimate that 2.0 mg kg À1 bw is the maximum likely exposure in the wild. All 31 Gyps vultures and the 20 other scavenging birds given meloxicam survived. Feeding behaviour remained normal and there were no significant differences between the treated and control groups in body mass, or the blood haematology and biochemistry parameters monitored, including those known to be affected by diclofenac (uric acid levels and alanine transferase activity). Meloxicam is used to treat a wide range of livestock ailments and is licensed and manufactured in India. We recommend that meloxicam be introduced as rapidly as possible across the Indian sub-continent as an alternative to diclofenac.