The effect of allopurinol on focal cerebral ischaemia: an experimental study in rabbits

Abstract

In this experimental study, the neuroprotective effect of the xanthine oxidase inhibitor allopurinol on focal cerebral ischaemia created by permanent middle cerebral artery occlusion (MCAO) was investigated. Using high performance liquid chromatography (HPLC), we measured hypoxanthine, xanthine, and uric acid (UA) levels in rabbit brains following focal cerebral ischaemia. Rabbits were randomly and blindly assigned into four groups of eight animals each. The control groups received 2% carboxymethylcellulose solution, while 10% allopurinol 150 mg/kg was given to the treatment group 1 h before ischaemia. Each group was subdivided into two groups which were sacrificed 4 h or 24 h after ischaemia, respectively. UA and xanthine values of the rabbits in the control groups were quite high at both times and highest after 24 h, particularly in the centre of the ischaemia. A significant decrease in UA and xanthine values was observed in rabbits that were given allopurinol (P<0.05). According to our results, it was concluded that allopurinol pretreatment protects neural tissue in the early period after arterial occlusion and prevents cerebral injury in the late period, especially in the perifocal area, possibly by preventing the formation of free radicals with xanthine oxidase inhibition.

Therapeutic Effects of Xanthine Oxidase Inhibitors: Renaissance Half a Century after the Discovery of Allopurinol

“…Similar to allopurinol in a rat model of transient middle cerebral artery occlusion, oxypurinol reduced the ischemic cerebral damage and attenuated the neurological deficits Phillis, 1991, 1992;Phillis and Lin, 1991). Allopurinol was also effective in a rabbit model of focal cerebral ischemia (Akdemir et al, 2001) and in hypoxic-ischemic injury models in rat pups, as well as in newborn lambs, even if its administration was delayed to the beginning of the reperfusion period (Palmer et al, 1990(Palmer et al, , 1993Shadid et al, 1998). Allopurinol, at relatively high doses, was also effective in transient middle cerebral occlusion models (Lindsay et al, 1991).…”

Proof of concept and feasibility studies examining the influence of combination ribose, adenine and allopurinol treatment on stroke outcome in the rat

“…Beneficial effect of allopurinol have been described in various animal models of brain injury including cerebral ischaemia (Akdemir et al, 2001;Ansari et al, 2013;Dong et al, 2015;Isik et al, 2005;Martz et al, 1989), but have been mostly described in terms of its antioxidant properties, although maintenance of the cerebral adenine nucleotide pool during ischaemia has been reported (Phillis et al, A one-way ANOVA was conducted across the three groups (Saline, RibAde and RibAdeAll). An unpaired t-test was conducted between saline and the combined treatment groups (RibAde and RibAdeAll).…”

Plasticity of purine release during cerebral ischemia: clinical implications?

“…The production of xanthine, which is not a substrate for purine salvage (Fig. 1), during cerebral metabolic stress in humans [83,84] and animals [62,[85][86][87][88] as well as loss of adenosine per se from the brain [15,16], likely contribute to reduced post-insult levels of adenine nucleotides. Indeed inhibition of xanthine oxidase has been shown to improve post-ischemic levels of adenine nucleotides [89] as has inhibition of adenosine transport, perhaps by reducing the loss of adenosine to the periphery [90].…”