Gene expression of antioxidant enzymes in experimental diabetic neuropathy

Chronic hyperglycemia results in a large deficit in nerve blood flow. Both autoxidative- and ischemia-induced lipid peroxidation occurs, with resultan t peripheral sensory neuropathy in streptozotocin-induced diabetes in the r at. Free radical defenses, especially involving antioxidant enzymes, have b een suggested to be reduced, but scant information is available on chronic hyperglycemia. We evaluated the gene expression of glutathione peroxidase, catalase, and superoxide dismutase (cuprozinc and manganese separately) in L4,5 dorsal root ganglion (DRG) and superior cervical ganglion, as well as enzyme activity of glutathione peroxidase in DRG and sciatic nerve in exper imental diabetic neuropathy of 3 months and 12 months durations. We also ev aluated nerve electrophysiology of caudal, sciatic-tibial, and digital nerv es. A nerve conduction deficit was seen in all nerves in experimental diabe tic neuropathy at both 3 and 12 months. Gene expression of glutathione pero xidase, catalase, cuprozinc superoxide dismutase, and manganese superoxide dismutase were not reduced in experimental diabetic neuropathy at either 3 or 12 months. Catalase mRNA was significantly increased in experimental dia betic neuropathy at 12 months. Glutathione peroxidase enzyme activity was n ormal in sciatic nerve. We conclude that gene expression is not reduced in peripheral nerve tissues in very chronic experimental diabetic neuropathy. Changes in enzyme activity may be related to duration of diabetes or due to post-translational modifications.