Electrophysiological and Biochemical Effects of Exposure to 2,5‐Hexanedione on Peripheral Nerve in Experimental Diabetic Rats

Abstract

DM could possibly be exposed to nhexane converted to 2,5-HD in liver. To clarify 2,5-HD influences on peripheral nerves in DM, electrophysiological and biochemical changes in DM rats were compared in 2,5-HD treated and untreated groups. Four groups of rats were studied: the Control group consisted of non-diabetic rats treated with a placebo; the HD group, of non-diabetic rats treated with 2,5-HD; the DM group, of diabetic rats treated with a placebo; the DM+HD group, of diabetic rats treated with 2,5-HD. 2,5-HD was administered at 100 mg/kg/day, five days a week for 8 weeks.The motor nerve conduction velocity (MCV) and motor distal latency (DL) in the rat's tails and glucose, fructose, sorbitol and myoinositol levels in the sciatic nerves were measured. The MCV in the DM+HD group was significantly reduced from the 4th week compared with those in the other groups.2,5-HD had no influence on the levels of glucose, fructose, sorbitol and myo-inositol in either the diabetic or non-diabetic group. These results indicated that exposure to 2,5-HD hastened the onset of peripheral neuropathy in experimental diabetic rats. This study indicates that 2,5-HD in combination with DM enhances the neurotoxicity. But the mechanisms of the neurotoxic interactions between 2,5-HD and DM are still unknown. It can be hypothesized that workers with hyperglycemia can suffer from neuropathy due to exposure to n-hexane earlier than those without hyperglycemia. (J Occup Health 1998; 40: 148-153) Key words: Neurotoxicity, Diabetes mellitus, 2,5-Hexanedione, Motor nerve conduction velocity, Motor distal latency, Glucose, Sorbitol, Fructose, Myo-inositol, RatThe compound 2,5-hexanedione (2,5-HD) is the neurotoxic metabolite of n-hexane, which is widely used as a solvent in industry and chemistry. 2,5-HD is known to produce peripheral neuropathy'' 2), which is indicated by progressive distal numbness in the limbs in humans. In severe cases, decreased motor nerve conduction velocity (MCV) is observed'-'). Indeed, the prevalence of patients with diabetes mellitus (DM) is very high 6) and many people with hyperglycemia work in industry. DM causes peripheral neuropathy as one of its chronic complications'), the signs of which are distal tingling paresthesia, pain and dysesthesia in the limbs', 9). Nevertheless, DM patients often show no symptoms in the beginning of this neuropathy, though decreased MCV is observed earlier than the onset of other symptoms. DM produces decreased MCV by increasing glucose levels and hyperactivity of the polyol pathway in peripheral nerve axons and Schwann cells10, "). Within the polyol pathway, glucose is reduced to sorbitol by aldose reductase coupled with the oxidation of NADPH to NADP+ in the first step in the pathway. Sorbitol is oxidized to fructose coupled with the reduction of NAD+ to NADH by sorbitol dehydrogenase in the second step in the pathway. Thus, the increase in polyol pathway activity results in the increase in sorbitol and fructose, and leads to a reduction in myo-inositol levels in peripheral ner...