Allopurinol-Induced Myocardial and Renal Damage in Nonarteriosclerotic (Virgin) and Arteriosclerotic (Breeder) Sprague-Dawley Rats

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Abstract
Non-arteriosclerotic (virgin) and arteriosclerotic (breeder), male Sprague-Dawley rats were treated with high (40 mg), moderate (10 mg) and low (5 mg) doses of the potent xanthine oxidase inhibiting agent, allopurinol. After 10 days of treatment, the animals began to die suddenly due to myocardial infarction, hepatic necrosis and nephrotoxic damage. Serum CPK [Creatine phosphokinase], SGOT [glutamic oxaloacetic transaminase] and LDH [lactate dehydrogenase] were abnormally elevated in the myocardial infarct prone breeder rats and the otherwise healthy, virgin rats commensurate with a high incidence of heart damage in the virgin and breeder rats. Although the high dose of allopurinol caused hepatic fatty infiltration, experimental animals were hypolipidemic. The severity of islet .beta. cell degranulation paralleled degree of hyperglycemia in all animals given allopurinol. Elevated BUN [blood urea nitrogen] levels, high circulating urate levels, hydronephrosis and urate stones were commensurate with allopurinol dose administered. Increased adrenal weight, hyperplasia, lipid depletion and abnormally high circulating Cmpd. B [compound B] levels, along with marked thymus gland involution, attested to the severe noxious effect of overdose with allopurinol. Apparently the unusual appearance of myocardial damage in the nonarteriosclerotic virgin and myocardial infarct-prone arteriosclerotic breeder rats is primarily related to cardiotoxic and nephrotoxic effects of large doses of allopurinol and secondarily to its hepatotoxic effects.