Fukudome Daisuke, Matsuda Maki, Kawasaki Toshiyuki, Ago Yukio, Matsuda Toshio
Laboratory of Medicinal Pharmacology, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamada-oka, Suita, Osaka 565-0871, Japan.
Eur J Pharmacol. 2008 Mar 31;583(1):164-9. doi: 10.1016/j.ejphar.2008.01.033. Epub 2008 Feb 5.
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.
依达拉奉是一种有效的羟基自由基清除剂，可减轻与氧化损伤相关的神经退行性疾病。先前的研究表明，氧化应激在糖尿病发病机制中起关键作用。本研究检测了依达拉奉对多次低剂量链脲佐菌素处理小鼠糖尿病的影响。连续五天用低剂量链脲佐菌素处理的小鼠出现进行性高血糖，糖尿病发病率增加。在注射链脲佐菌素期间每日给予依达拉奉，以剂量依赖的方式抵消了多次低剂量链脲佐菌素诱导的高血糖。依达拉奉可防止多次低剂量链脲佐菌素诱导的胰腺胰岛素减少。在最后一次注射链脲佐菌素后给予依达拉奉时，也观察到了其抑制作用。组织化学检查显示，多次低剂量链脲佐菌素处理导致胰岛单核细胞浸润，随后出现高血糖，而依达拉奉显著抑制了多次低剂量链脲佐菌素诱导的胰岛炎。多次低剂量链脲佐菌素处理还增加了小鼠胰腺组织中脂质过氧化产物硫代巴比妥酸反应物质，而依达拉奉完全抑制了这种作用。这些发现表明，即使在链脲佐菌素处理后，依达拉奉也可通过清除自由基来抵消多次低剂量链脲佐菌素诱导的糖尿病的发展，自由基可能是胰岛β细胞免疫破坏的介质。
