An aldose reductase inhibitor reverses early diabetes-induced changes in peripheral nerve function, metabolism, and antioxidative defense

SPECIFIC AIMSAldose reductase inhibitors (ARIs) prevent peripheral nerve dysfunction and morphological abnormalities in animal models of diabetes. However, some experimental intervention studies and clinical trials of ARIs on diabetic neuropathy (DN) appeared disappointing because of either 1) their inadequate design and, in particular, insufficient correction of the sorbitol pathway activity or 2) the inability to reverse established functional and metabolic deficits of DN by AR inhibition in general. Moreover, it has recently been hypothesized that the key physiological role of AR is the detoxification of lipid peroxidation products, and thus inhibition of the enzyme under diabetic conditions could actually be detrimental rather than beneficial. The present study was therefore designed 1) to evaluate whether diabetes-induced neurovascular dysfunction, nerve conduction deficits, and the key metabolic abnormalities can be reversed by treatment with an adequate dose of ARI, i.e., a dose that completely inh...