Beneficial remedy by probucol but exacerbation by endotoxin of the diabetic neuropathy and myopathy in mice

• Main Authors: Lu, Chia-Hsin, 盧佳欣
• Other Authors: Lin-Shiau, Shoei-Yn
• Format: Others
• Language: zh-TW
• Published: 1997
• Online Access: http://ndltd.ncl.edu.tw/handle/93956950094388976964

碩士 === 國立臺灣大學 === 毒理學研究所 === 85 === Diabetic neuropathy and myopathy are major complication in diabetic patients. It has been suggested that diabetic neuropathy is closely related to diabetic myopathy. Recently, many studies have demonstrated that free radical paly an important role in the pathogenesis of islet cell destruction in type I diabetes. Besides, a role for antioxidants in preventing IDDM have been demonstrated. Oxygen free radicals have been claimed to paly an important role in pathogenesis of diabetic neuropathy. In the present study, we attempted to address this working hypothesis by administration of an antioxidant probucol and/or endotoxin (lipopolysaccharide, LPS, an enhancer of free radical production) during the diabetic procession by streptozotocin infection in mice. The results showed that probucol administration certainly, although not completely, reduced blood sugar, water intake, urine excretion and improved the complications of diabetic neuropathy (motor nerve conduction velocity, rotarod motor activity and balancing ability as well as high frequency stimulation-induced synaptic fatigue). By contrast, LPS appears to exaggerate symptoms of the diabetic complications, but coadministration with probucol still showed its effectiveness in the improvement of the illness. However, discontinuous administration of probucol for one week, the blood sugar gradually increased. By measurement of the nitric oxide concentration in blood, the protein level and mRNA level of nitric oxide synthase, we suggest that free radical generation especially during bacterial infection appears to play a role in the pathogenesis of diabetic complications including neuropathy. Antioxidants such as probucol can be a beneficial remedy for the diabetic complications, but continuous administation seems to be needed for this achievement.