Comparative studies of xanthine oxidase inhibitors viz. allopurinol and febuxostat against induced hyperuricaemia in a poultry model.

In this study, an attempt was made to evaluate the relative efficacy of two important anti-gout agents, viz. allopurinol and febuxostat, in the control of hyperuricaemia/gout using a poultry model. A 21-day study was conducted on 48 Vencobb-400 broiler chicks randomly divided into four groups. In one group hyperuricaemia/gout was induced by the oral administration of diclofenac (group D); in two other groups the ameliorative effect of the two drugs under study was investigated by providing both simultaneously, i.e. diclofenac and allopurinol (group DA), diclofenac and febuxostat (group DF); and the fourth group was kept un-induced and untreated as a control (group C). Both allopurinol and febuxostat inhibit xanthine oxidase enzymes, thereby reducing the production of uric acid. The birds kept on diclofenac alone exhibited the highest level of hyperuricaemia, clinical signs of gout, and overt adverse changes in the visceral organs, whereas these changes were lesser in allopurinol- and febuxostat-treated groups. Furthermore, haematological, biochemical, patho-morphological, and ultra-structural studies using transmission electron microscopy were carried out to evaluate the pathology and, thus, the ameliorative effect of allopurinol and febuxostat. The findings proved that allopurinol and febuxostat carry definite ameliorative potential as anti-hyperuricemic and anti-gout agents in poultry, which was better expressed by febuxostat compared to allopurinol.

"Free" copper: a new endogenous chemical mediator of inflammation in birds.

For acceptance of any chemical agent as an endogenous chemical mediator of inflammation, the agent in question must fulfill some biological requirements which are (a) it should be ubiquitously present in tissues in inactive form, (b) it should be activated during process of inflammation whose increase should be identifiable, (c) it should induce or amplify some events of inflammation, (d) there must be some natural inhibitor of such active form in tissues, (e) it should be able to induce inflammatory reaction after exogenous injection, (f) such reaction should be inhibited by exogenous use of their antagonists, and (g) it should be amplified by use of agonists. Copper in its protein free or protein bound form are reported to act as pathogenic factor in inflammatory processes due to oxidative stress. But their role as endogenous chemical mediator of inflammation does not appear to be investigated thoroughly in light of abovementioned biological criterion of mediator. Present study aims at thorough exploration on role of free copper as endogenous chemical mediator of inflammation in light of above facts. It was done by estimation of total copper, protein-bound copper, and free copper along with estimation of free radical generation, increase in vascular permeability, and cellular infiltration during acute inflammatory reaction induced by carrageenan and concanavalin using chicken skin as test model. It was further evaluated by use of exogenous free copper in experimental model and their subsequent inhibition and amplification by chemical chelators of copper. Present study confirms that free copper fulfilled all the biological requirements for accepting it as an endogenous chemical mediator of inflammation.