Protective Effect of Vitamin E on Nerve Conduction and Dorsal Root Ganglia Against Cisplatin-Induced Peripheral Neurotoxicity in Rats

Background: Cisplatin is commonly used against several solid tumors. Severe peripheral neuropathy is a major clinical issue affecting 1040% of patients treated with cisplatin and is associated with apoptosis of sensory dorsal root ganglia. Vitamin E is one of the several substances with suggested effects on peripheral nerves but still its exact benefit is not clear. The aim of this study is to investigate the possible protective effect of a-tocopherol the active form of vitamin E on cisplatin-induced peripheral neurotoxicity in rats. Methods: The study included four groups: Control, cisplatin, vitamin E-control and cisplatin-vitamin E groups. Twentyfour hours after the end of treatments, tail sensory nerve and sciatic motor nerve conduction velocities were conducted also the histopathology of the sciatic nerve was studied. The sciatic dorsal root ganglia (DRG) malondialdehyde (MDA), superoxide dismutase (SOD) activity, glutathione, NF-kappa B (NF-KB) and antiapoptotic Bc1-2, apoptotic Bax and caspase3 expression as well as serum TNF-cit were measured. Results: Cisplatin (2mg/kg/twice weekly, in a total of eight intraperitoneal injections) significantly decreased sensory nerve conduction velocity without affecting the motor nerve conduction velocity and caused sciatic nerve axonal degeneration with loss of myelination. Cisplatin also increased dorsal root ganglia MDA level, NF-KB, Bax and caspase-3 expression as well as serum TNF-cit and decreased dorsal root ganglia superoxide dismutase activity and glutathione levels and Bcl2 expression in the cisplatin group compared to the control group. Oral vitamin E (daily oral a-tocopherol 1000mg/kg) concomitant with the cisplatin doses, significantly improved the sensory nerve conduction velocity, preserved sciatic nerve fibers morphology, decreased dorsal root ganglia MDA level and NF-KB, Bax and caspase-3 expression and serum TNFa and increased DRG superoxide dismutase and glutathione levels and Bc1-2 expression in the cisplatin-vitamin E group compared to the unprotected cisplatin group. Conclusion: Vitamin E has potential neuro protective effects in cisplatin-induced sensory neuropathy linked to its anti-oxidant, anti-inflammatory and anti-apoptotic actions on dorsal root ganglia which may spark its future use in clinical settings. Correspondence to: Dr. Sandra M. Younan, The Department of Physiology, Faculty of Medicine, Cairo University, E-mail: [email protected]