ABSTRACT
To assess the contribution of oxidative stress in the pathophysiology of diabetic neuropathy and the possible protective effect of L-carnitine, coenzyme Q 10 [CoQ10] and acetylsalicylic acid [ASA] in streptozotocin-included diabetic neuropathy in rats. We also examined whether the studied drugs can promote satisfactory regeneration of sciatic nerve fibers following sciatic nerve crushing. Twenty rats were used as control and were divided into two groups. 10 rats each: Group I a was injected intraperitoneal [i.p.] by a single dose of saline and served as a control for group II a, group I b similar to group I a but with induced sciatic nerve crushing and served as control for group II b. Eighty rats were made diabetic by i.p streptozotocin [STZ] injection and were divided into: group II a [STZ-injected rats], group II b [STZ-injected rats with sciatic nerve crushing], groups III a, IV a and V a [STZ-injected rats treated with L-carnitine, CoQ1O and ASA respectively, for six weeks starting one week following STZ injection], groups III b, IV b and V b [STZ-injected rats,with sciatic nerve crushing, that received the same drugs as groups III a, IV a and V a]. At the end of the experimental period, distal motor latency [DL], maximum peak and peak to peak amplitude of compound muscle action potential [CMAP] were measured by percutaneous sciatic nerve stimulation. Blood samples were collected for measurement of plasma glucose and malondialdehyde [MDA] concentrations. The sciatic nerve was isolated for measuring reduced glutathione [GSH] concentration. STZ-injection induced diabetes, evidenced by significant higher mean value in plasma glucose concentration in groups IIa and IIb compared to that of the control groups Ia and Ib respectively. Significant sciatic nerve dysfunction could be observed, in the form of significantly prolonged DL and significantly decreased maximum peak and peak to peak amplitude of CMAP, in groups IIa and IIb compared to the control groups Ia and Ib respectively. STZ-injection resulted in oxidative stress evidenced by significant higher mean value in plasma MDA concentration and significant lower mean value in sciatic nerve GSH concentration in groups IIa and IIb compared to the control groups Ia and Ib respectively. Sciatic nerve crushing in group I b resulted in significant prolongation of DL and significant decrease in maximum peak and peak to peak amplitude of CMAP compared to group I a. Sciatic nerve crushing in group I b also resulted in significant lower mean value of sciatic nerve GSH concentration compared to group I a. The use of L-carnitine, CoQ10 as well as ASA, did not cause a significant change in plasma glucose concentration nor in body weight compared to groups IIa and IIb. The use of the above mentioned drugs improved oxidative stress parameters evidenced by significant lower mean value in plasma MDA concentration and significant higher mean value in sciatic nerve GSH concentration compared to groups IIa and IIb. The increase in sciatic nerve GSH concentration in groups III b and IV b that received L-carnitine and CoQ10 respectively, was significant compared to group Vb that received ASA as an antioxidant, whereas no significant difference in plasma MDA was found between different drug-treated groups. The use of the studied drugs resulted in significant improvement of DL as well as significant increase in maximum peak and peak to peak amplitude of CMAP compared to groups IIa and IIb. Group V a showed significant higher mean value in the maximum peak and peak to peak amplitude of CMAP compared to groups III a and IV a. Also group V b showed significant higher mean value in the maximum peak and peak to peak amplitude of CMAP compared to group III b. The results of the present study support the hypothesis that oxidative stress plays a key role in the pathophysiology of diabetic neuropathy and demonstrate that the use of antioxidants might have a protective role against diabetic neuropathy as well as a role in enhancing regeneration of functional nerve fibers. We recommend further human studies to evaluate the role of the addition of natural antioxidants, like L-carnitine or CoQ10, as well as ASA to the treatment regimen of diabetes, from the onset of the disease, in protection against diabetic neuropathy