The effects of zenarestat, an aldose reductase inhibitor, on peripheral neuropathy in Zucker diabetic fatty rats.

We studied the effects of zenarestat, an aldose reductase inhibitor (ARI), on peripheral neuropathy in Zucker diabetic fatty (ZDF) rats, an animal model of type 2 diabetes. ZDF rats and their lean rats counterparts were fed a sucrose-containing diet, and zenarestat was given orally once a day for 8 weeks. Motor nerve conduction velocity (MNCV), F-wave minimal latency (FML), and sorbitol concentrations in the sciatic nerve were measured. In ZDF control rats, a remarkable accumulation of sorbitol, a delay in FML, and a slowing of MNCV were observed compared with lean rats. At a dose of 3.2 mg/kg, zenarestat had no significant effect on the delay in FML and the slowing of MNCV, although the sorbitol accumulation in the sciatic nerve was partially inhibited in ZDF rats. On the other hand, 32 mg/kg zenarestat treatment improved these nerve dysfunctions in ZDF rats, along with a reduction of nerve sorbitol accumulation almost to the level of lean rats. These data showed that zenarestat improved diabetic peripheral neuropathy in ZDF rats, a type 2 diabetes model, providing evidence for the therapeutic potential of zenarestat for the treatment of diabetic neuropathy.