Effects of nitric oxide synthase inhibitors and melatonin on the hyperglycemic response to streptozotocin in rats.
Recent studies evidence that peroxynitrite is spontaneously formed when nitric oxide (NO) and superoxide coexist and suggest that it is likely to be involved in the destruction of the pancreatic beta cells. We examined whether drugs that inhibit nitric oxide synthase (NOS) or scavenge peroxynitrite could abrogate STZ-induced hyperglycemia in rats. Blood glucose levels were measured before (0 h) and 24, 48, and 72 h following intraperitoneal administration of 60 mg/kg streptozotocin (STZ). The levels of blood sugar in STZ-treated control animals were significantly elevated at all time points of observation with a peak increase at 48 h. The hyperglycemic response of STZ was found to be significantly reduced in animals pretreated with aminoguanidine (50 mg/kg i.p.), an inducible isoform-selective NOS (iNOS) inhibitor with antioxidant property, and by melatonin (6 mg/kg i.p.), an antioxidant that also prevents peroxynitrite formation but not by Nw-nitro-L-arginine methyl ester (L-NAME, 10 mg/kg i.p.), and 7-nitroindazole (7-NI, 50 mg/kg i.p.), the constitutive inhibitors of endothelial and neuronal NOS, respectively. These findings indicate the possible participation of iNOS-derived NO as well as oxygen free radicals in STZ-induced pancreatic beta cell destruction and compounds that act as scavengers of peroxynitrite may offer protection against such a damage.
Rao
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Department of Physiology and Pharmacology, Federal University of Ceará, P.O. Box 3157, Rua Cel. Nunes de Melo 1127, 60430-270 Fortaleza, CE, Brazil. vietrao@ufc.br
Santos
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Silva
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Teixiera
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D000704:Analysis of Variance; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001786:Blood Glucose / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006146:Guanidines / Q000494:pharmacology; D007191:Indazoles / Q000494:pharmacology; D007274:Injections, Intraperitoneal; D008297:Male; D008550:Melatonin / Q000494:pharmacology*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D051381:Rats; D017208:Rats, Wistar; D013311:Streptozocin
D000975:Antioxidants; D001786:Blood Glucose; D004791:Enzyme Inhibitors; D006146:Guanidines; D007191:Indazoles; D013311:Streptozocin; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496322:Nos1 protein, rat; C496318:Nos2 protein, rat; C496316:Nos3 protein, rat; D008550:Melatonin; C004479:pimagedine; C080122:7-nitroindazole; D019331:NG-Nitroarginine Methyl Ester