Mechanisms of streptozotocin- and alloxan-induced damage in rat B cells.
In studies to evaluate possible inhibitors of the B-cell toxin, streptozotocin, the superoxide scavenger, superoxide dismutase, did not prevent or reduce the toxic effects of streptozotocin as determined by loss of insulin secretion from rat pancreatic B cells in monolayer culture. However, 1,1-dimethyl urea, a scavenger of the hydroxyl radical, did afford significant protection. Both scavengers diminished the cytotoxic effects of alloxan. The inhibitors of poly (ADP-ribose) synthetase, 3-aminobenzamide and nicotinamide, also were effective in attenuating alloxan- and streptozotocin-induced B-cell toxicity. Tests of the hydroxyl-scavenging ability of the three streptozotocin antagonists revealed that 3-aminobenzamide, nicotinamide and 1,1-dimethyl urea were effective scavengers of this free radical. Conversely, 1,1-dimethyl urea, although not as potent as 3-aminobenzamide or nicotinamide, was found to inhibit poly (ADP-ribose) synthetase. These data indicate that these chemicals most likely attenuate alloxan-induced toxicity by scavenging the hydroxyl radical and diminish streptozotocin-induced toxicity by inactivation of the poly (ADP-ribose) system.
D000496:Alloxan / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn; D001549:Benzamides / Q000494:pharmacology; D002478:Cells, Cultured; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D007700:Kinetics; D008782:Methylurea Compounds / Q000494:pharmacology; D009536:Niacinamide / Q000494:pharmacology; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D051381:Rats; D013311:Streptozocin / Q000494:pharmacology*; D013482:Superoxide Dismutase / Q000494:pharmacology
D001549:Benzamides; D007328:Insulin; D008782:Methylurea Compounds; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D009536:Niacinamide; D013311:Streptozocin; D000496:Alloxan; C025160:3-aminobenzamide; D013482:Superoxide Dismutase; C018275:1,1-dimethylurea