Reduction in the diabetogenic effect of alloxan in mice by treatment with the antineoplastic agent ICRF-187.
Blood glucose concentrations were markedly elevated in CD-1 mice 48 hr after iv administration of alloxan (75 mg/kg). Treatment with three doses of ICRF-187 (96 to 345 mg/kg) given 60 min before and 4 and 8 hr after alloxan significantly attenuated the increase in blood glucose. Pretreatment with dimethyl sulfoxide (DMSO), a known free radical scavenger, at doses of 3.5 to 7.3 g/kg also protected against the alloxan diabetogenic action. When the lowest doses of ICRF-187 (96 mg/kg) and DMSO (3.5 g/kg) were combined, alloxan exerted no hyperglycemic effect. The protective effects of ICRF-187 and DMSO were confirmed morphologically. In alloxan-treated animals, beta cell granules were absent. In contrast, the degree of granulation showed only a mild to moderate reduction in those alloxan-treated animals given ICRF-187 alone, DMSO alone, or the combination of ICRF-187 and DMSO. These results suggest that ICRF-187 may alter the mechanism of free radical generation thought to be responsible for the production of alloxan diabetes.
D000496:Alloxan / Q000037:antagonists & inhibitors*; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D002614:Chelating Agents / Q000494:pharmacology; D003921:Diabetes Mellitus, Experimental / Q000517:prevention & control*; D004305:Dose-Response Relationship, Drug; D005609:Free Radicals; D007515:Islets of Langerhans / Q000473:pathology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D010879:Piperazines / Q000627:therapeutic use*; D011929:Razoxane / Q000494:pharmacology / Q000627:therapeutic use*
D001786:Blood Glucose; D002614:Chelating Agents; D005609:Free Radicals; D010879:Piperazines; D011929:Razoxane; D000496:Alloxan