| Summary: | 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.
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