El-Hage A N, Herman E H, Ferrans V J
Res Commun Chem Pathol Pharmacol. 1981 Sep;33(3):509-23.
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.
给CD - 1小鼠静脉注射四氧嘧啶（75毫克/千克）48小时后，其血糖浓度显著升高。在四氧嘧啶给药前60分钟以及给药后4小时和8小时给予三剂ICRF - 187（96至345毫克/千克）进行治疗，可显著减轻血糖的升高。以3.5至7.3克/千克的剂量用已知的自由基清除剂二甲基亚砜（DMSO）进行预处理，也可防止四氧嘧啶的致糖尿病作用。当将最低剂量的ICRF - 187（96毫克/千克）和DMSO（3.5克/千克）联合使用时，四氧嘧啶未产生高血糖作用。ICRF - 187和DMSO的保护作用在形态学上得到了证实。在四氧嘧啶处理的动物中，β细胞颗粒缺失。相比之下，在单独给予ICRF - 187、单独给予DMSO或ICRF - 187与DMSO联合使用的四氧嘧啶处理动物中，颗粒化程度仅显示轻度至中度降低。这些结果表明，ICRF - 187可能改变了被认为是导致四氧嘧啶糖尿病产生的自由基生成机制。
