The radical scavenger edaravone counteracts diabetes in multiple low-dose streptozotocin-treated mice.
Edaravone is a potent scavenger of hydroxyl radicals and attenuates oxidative damage-related neurodegenerative diseases. Previous studies suggest that oxidative stress plays a key role in the pathogenesis of diabetes. The present study examined the effect of edaravone on diabetes in multiple low-dose streptozotocin-treated mice. Mice treated with low-doses of streptozotocin for five consecutive days showed progressive hyperglycemia and an increased incidence of diabetes. Daily treatment with edaravone during the streptozotocin injections counteracted the multiple low-dose streptozotocin-induced hyperglycemia in a dose-dependent manner. Edaravone protected against the multiple low-dose streptozotocin-induced reduction in pancreatic insulin. The suppressive effects of edaravone were also observed when it was administered after the last injection of streptozotocin. Histochemical examination showed that multiple low-dose streptozotocin treatment caused mononuclear cell infiltration in pancreatic islets, followed by hyperglycemia, and that edaravone significantly inhibited the multiple low-dose streptozotocin-induced insulitis. Multiple low-dose streptozotocin treatment also increased the lipid peroxidation product thiobarbituric acid reactive substance in pancreatic tissues of mice, and this effect was completely inhibited by edaravone. These findings suggest that edaravone, even after streptozotocin treatment, counteracts the development of multiple low-dose streptozotocin-induced diabetes by scavenging free radicals, which are possible mediators of the immune destruction of islet beta cells.
Fukudome
Daisuke
D
Laboratory of Medicinal Pharmacology, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamada-oka, Suita, Osaka 565-0871, Japan.
Matsuda
Maki
M
Kawasaki
Toshiyuki
T
Ago
Yukio
Y
Matsuda
Toshio
T
D000818:Animals; D000983:Antipyrine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D001786:Blood Glucose / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy*; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy; D000077553:Edaravone; D016166:Free Radical Scavengers / Q000627:therapeutic use*; D006943:Hyperglycemia / Q000188:drug therapy; D007004:Hypoglycemic Agents; D007328:Insulin / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010179:Pancreas / Q000187:drug effects / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
D001786:Blood Glucose; D016166:Free Radical Scavengers; D007004:Hypoglycemic Agents; D007328:Insulin; D017392:Thiobarbituric Acid Reactive Substances; D000077553:Edaravone; D000983:Antipyrine