Effects of a fructose-rich diet and the aldose reductase inhibitor, ONO-2235, on the development of diabetic neuropathy in streptozotocin-treated rats

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Abstract
Streptozotocin-diabetic rats were maintained on a 72% fructose diet for 4 wk and some were treated with an aldose reductase inhibitor (either alrestatin: 0.9 g .cntdot. kg-1 .cntdot. day-1 or ONO-2235: 50 mg .cntdot. kg-1 .cntdot. day-1). Fructose feeding significantly influenced the development of impaired motor nerve conduction velocity in the diabetic rats and this effect was positively correlated with sorbitol accumulation in the sciatic nerve of diabetic rats maintained on a fructose-rich diet. Treatment with ONO-2235, a new aldose reductase inhibitor, prevented both slowing of motor nerve conduction velocity and elevation of nerve sorbitol concentration. Erythrocyte sorbitol levels were significantly correlated to those of the sciatic nerve (r = 0.86, p < 0.001) and the retina (r = 0.91, P < 0.001) in these animals. These findings suggest that increased polyol pathway activity may be related to the pathogenesis of diabetic neuropathy and erythrocyte sorbitol concentrations may prove a useful indicator for the presence of diabetic complications.