Effect of allopurinol on ischemia and reperfusion-induced cerebral injury in spontaneously hypertensive rats.

Abstract

In spontaneously hypertensive rats, we studied the participation of xanthine oxidase-linked free radical in ischemia and reperfusion-induced cerebral injury, using allopurinol, a xanthine oxidase inhibitor. The loss of righting reflex was noted in some animals after a 4 hour occlusion of bilateral common carotid arteries and 19 of 25 animals died within 72 hours after reperfusion. One hour after reperfusion, the cerebral water content increased significantly, with an increase in sodium content and a decrease in potassium content. In 7 animals treated with oral administrations of allopurinol (200 mg/kg) 24 hours and 1 hour before occlusion, no death was found either during occlusion or after reperfusion, and the loss of righting reflex was noted in only one animal 24-72 hours following reperfusion. The increase in cerebral water content and accompanied changes in electrolyte contents were clearly prevented by allopurinol. These results suggest the possibility that the production of xanthine oxidase-linked free radical participates in cerebral injury due to ischemia and reperfusion in spontaneously hypertensive rats.

β-Hydroxybutyrate, a Cerebral Function Improving Agent, Protects Rat Brain Against Ischemic Damage Caused by Permanent and Transient Focal Cerebral Ischemia

“…This implies that some mechanism to generate oxygen radicals still works and aggravates ischemic damage in permanent ischemia caused by occluding cerebral arteries. Allopurinol reduced infarct volume of cortical tissue more effectively than caudate tissue (11), suggesting that a collateral blood supply existed in the cortical area where the branches of MCA have extensive anastomoses with distal branches of the anterior and posterior cerebral arteries (12). During the period of ischemia, the depletion of tissue ATP due to the restriction of its production results in an elevated concentration of AMP.…”

Nephrotoxicity of allopurinol is enhanced in experimental hypertension.

“…This adverse reaction to chronic allopurinol administration is in sharp contrast to the benefits of this drug in other organ systems (e.g., it attenuates ischemia and reperfusion-induced cerebral injury in this hypertensive strain). 20 We used the endogenous creatinine clearance as an index of the glomerular filtration rate and kidney function. There are inherent inaccuracies with this method due to incomplete bladder emptying and a variable contribution of tubular secretion to creatinine excretion.…”

Superoxide radical generation and histopathological changes in hippocampal CA1 after ischaemia/ reperfusion in gerbils

“…However, it takes longer for the hypoxanthine-xanthine oxidase system and activated neutrophils to generate superoxide radicals, sl-36 Therefore, excessive generation of superoxide radicals on the third and fifth days after reperfusion in the present study may result from the hypoxanthine-xanthine oxidase system and from activated neutrophils. Ito et al 37 reported amelioration of ischaemia/reperfusion cerebral damage by administering a xanthine oxidase inhibitor. Shiga et al ss reported that pretreatment of monoclonal antibody ofneutrophils inhibited the brain oedema on the day following a transient ischaemia, probably due to exhaustion of circulatory neutrophils.…”