Slowing of peripheral motor nerve conduction was ameliorated by aminoguanidine in streptozocin-induced diabetic rats

Abstract

The aims of this study were to investigate the effect of aminoguanidine (AG) on slowing of motor nerve conduction velocity (MNCV) of the sciatic nerve in streptozocin-induced diabetic rats and to assess its mechanism of action. The MNCV of the sciatic nerve was measured electrophysiologically in diabetic rats treated with and without AG for 16 weeks. To elucidate the action of AG, morphological lesion and abnormality of polyol pathway metabolism in the nerve were examined and tissue levels of advanced glycosylation end-products (AGE) were determined as an indicator of AGE accumulation in tissue. Diabetic rats were treated with AG at three doses of 10, 25 and 50 mg/kg for 16 weeks. Myelinated fiber morphometry and nerve Na+,K(-)-ATPase activity were determined. The AGE levels in renal cortex were measured by a specific ELISA. Aminoguanidine dose-dependently ameliorated slowing of MNCV 16 weeks after the treatment without changing body weight or blood glucose levels. No difference in myelinated fiber morphometry or Na+,K(+)-ATPase activity with or without AG treatment was detected in diabetic rats. Diabetes increased the AGE level in the renal cortex by six times compared to non-diabetic rats, and AG reduced the rise in the AGE level by 40%. The MNCV was inversely correlated with the AGE levels. We conclude that improvement of conduction slowing by AG in experimental diabetes may be through decreasing the AGE level in the peripheral tissues. Aminoguanidine may have a therapeutic potential in controlling diabetic peripheral neuropathy.

Effect of Treating Streptozotocin‐Induced Diabetic Rats With Sorbinil, Myo‐Inositol or Aminoguanidine on Endoneurial Blood Flow, Motor Nerve Conduction Velocity and Vascular Function of Epineurial Arterioles of the Sciatic Nerve

“…As has been previously reported, we demonstrate that treating streptozotocin-induced diabetic rats with sorbinil or aminoguanidine significantly improves the reduction in EBF and slowing of MNCV [3][4][5][6][7][8][9][10][11][12][24][25][26][27][28]. In sorbinil treated diabetic rats EBF and MNCV remained suppressed by 15 and 18%, respectively compared to controls, whereas in aminoguanidine treated rats EBF and MNCV, compared to controls, was decreased by 6 and 16%, respectively.…”

“…We have previously shown that endothelialdependent vascular relaxation of arterioles that provide circulation to the region of the sciatic nerve is impaired by diabetes [35,36]. In the present study we sought to determine the effect treatment of diabetic rats with sorbinil, an aldose reductase inhibitor, aminoguanidine, an inhibitor of nonenzymatic glycation, or myoinositol supplementation has on EBF, MNCV as well as vascular relaxation of arterioles that provide circulation to the region of the sciatic nerve.As has been previously reported, we demonstrate that treating streptozotocin-induced diabetic rats with sorbinil or aminoguanidine significantly improves the reduction in EBF and slowing of MNCV [3][4][5][6][7][8][9][10][11][12][24][25][26][27][28]. In sorbinil treated diabetic rats EBF and MNCV remained suppressed by 15 and 18%, respectively compared to controls, whereas in aminoguanidine treated rats EBF and MNCV, compared to controls, was decreased by 6 and 16%, respectively.…”

“…Based on these studies pharmacological compounds, like aldose reductase inhibitors and anti-glycation agents, have been developed for the treatment of diabetic neuropathy [59]. In diabetic animal models these agents have been shown to improve nerve function and endoneurial blood flow [3][4][5][6][7][8][9][10][11][12][24][25][26][27][28]. However, studies on the effect these agents may have on vascular function of vessels that provide circulation to nerves have been limited.…”

“…Treatment of diabetic rats with aminoguanidine, an inhibitor of the formation of advanced glycosylation end products [23], ameliorates the slowing of motor nerve conduction velocity and reduction of endoneurial blood flow [24][25][26][27][28]. This suggests that the formation of advanced glycation end products in the nerve or vascular tissue perturbs neural function [29][30][31][32].…”

Medical treatment of diabetic retinopathy

“…There are several published reports on the ability of aminoguanidine to inhibit AGE formation in vivo. [68][69][70][71][72][73][74][75][76][77] A recent report showed the ability of aminoguanidine to prevent the development of diabetic retinopathy in diabetic dogs followed for 5 years. 78 Optimism for the clinical use of aminoguanidine has been tempered by the gradual realisation that aminoguanidine also inhibits a range of other important pathways, most notably generation of nitric oxide by eNOS, which may increase nonspecific and unwanted side effects of the drug.…”