Protection against isoproterenol-induced myocardial necrosis in rats by 6-mercaptopurine and 6-thioguanine or by irradiation.
Isoproterenol produces myocardial necrosis in rats. To investigate the possible role of oxygen free radicals generated by xanthine oxidase and neutrophils, we examined the effects of the xanthine oxidase inhibitors, 6-mercaptopurine (6MP) and 6-thioguanine (6TG) combined and allopurinol, or of irradiation (to induce leukopenia) on isoproterenol-induced myocardial necrosis (ISOMN). The incidence and severity of ISOMN was significantly reduced by 6MP + 6TG but not by the specific inhibitor of xanthine oxidase, allopurinol, indicating that the protective effects of 6MP + 6TG may be due to its free radical scavenging activity rather than its xanthine oxidase inhibitory activity. Irradiation provided complete protection against ISOMN in all rats. Marked leukopenia or other radiation-induced protective factors could play a role in the mechanism of the protection.
Joseph
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Division of Research and Testing, Food and Drug Administration, Washington, D.C. 20204.
Balazs
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D000493:Allopurinol / Q000494:pharmacology; D000818:Animals; D006331:Heart Diseases / Q000139:chemically induced / Q000517:prevention & control*; D007545:Isoproterenol / Q000037:antagonists & inhibitors* / Q000633:toxicity; D007962:Leukocytes / Q000187:drug effects / Q000502:physiology; D007970:Leukopenia / Q000503:physiopathology; D008297:Male; D015122:Mercaptopurine / Q000494:pharmacology*; D009206:Myocardium / Q000473:pathology; D009336:Necrosis; D011833:Radiation Injuries, Experimental / Q000097:blood; D051381:Rats; D011919:Rats, Inbred Strains; D013866:Thioguanine / Q000494:pharmacology*
D000493:Allopurinol; D015122:Mercaptopurine; D013866:Thioguanine; D007545:Isoproterenol