gamma-linolenic-acid and Ischemia

A reduction in nerve conduction velocity and an increase in resistance to ischemic conduction failure are early signs of neural dysfunction in both diabetic patients and animal models of diabetes. The effect of Bimoclomol (BRLP-42), a drug under clinical development for the treatment of diabetic complications, on experimental peripheral neuropathy was examined in rats made diabetic by injection of streptozotocin. Daily oral doses of Bimoclomol (10 or 20 mg/kg) or control dose of gamma-linolenic acid (260 mg/kg), an agent with known neuropathy-improving effects, were administered for 3 months. Treatments began 1 day after diabetes induction to assess the prophylactic efficacy of Bimoclomol. Neuropathy was evaluated electrophysiologically by measuring motor and sensory nerve conduction velocities and resistance to ischemic conduction failure of sciatic nerve in vivo. Bimoclomol significantly reduced nerve conduction slowing and retarded the typical elevated ischaemic resistance due to streptozotocin-induced neuropathy, suggesting that the drug might be a useful treatment for diabetic peripheral neuropathies.

Topics: Animals; Blood Glucose; Diabetes Mellitus, Experimental; Diabetic Neuropathies; Electromyography; gamma-Linolenic Acid; Ischemia; Male; Neural Conduction; Piperazines; Pyridines; Rats; Rats, Wistar; Sciatic Nerve; Vascular Resistance; Vasodilator Agents

In rats with 6 weeks streptozotocin-diabetes there was a 53% reduction in sciatic nerve laser Doppler flux compared to controls (p < 0.01). Treatment of a parallel group of diabetic rats with evening primrose oil, by dietary admixture throughout the protocol, prevented this ischaemia (Doppler flux was 91% of evening primrose-oil-treated controls and was not significantly different). There were no differences in systemic arterial pressure. In another experiment evening primrose oil markedly antagonised the development of exaggerated resistance to anoxic conduction failure in sciatic nerves from diabetic rats. The resistance to anoxia of nerves from non-diabetic rats was also reduced by evening primrose oil. These observations suggest that the sciatic nerves of diabetic rats with short-term streptozotocin-diabetes are markedly ischaemic and that this ischaemia is involved in the development of increased resistance to anoxic/ischaemic conduction failure in diabetic nerve. The findings also promote evening primrose oil as a potential treatment to prevent nerve ischaemia.

Topics: Animals; Blood Glucose; Blood Pressure; Coconut Oil; Diabetes Mellitus, Experimental; Diabetic Nephropathies; Dietary Fats; Fatty Acids, Essential; gamma-Linolenic Acid; Hypolipidemic Agents; Ischemia; Linoleic Acids; Male; Neural Conduction; Oenothera biennis; Plant Oils; Rats; Rats, Wistar; Sciatic Nerve