Synergistic neroprotective activiity of benfotiamine co administered with erythropoietin in chemotherapy induced peripheral neuropathy in rats

Author(s): Hariprasad M.G.*, Rema Razdan, Yasha T.C.

Abstract

Chemotherapeutic drugs like Cisplatin, Taxols used in cancer are associated with the development of peripheral neuropathy (PN). Severe neuropathy can occur in 3% to 7% of treated cases with single agents but the severity can increase to 38% with combined regimens. The treatment options for PN currently include anti-depressants, anti-convulsants and opioid analgesics. These agents are modestly effective for symptomatic relief, but they neither affect the underlying pathology nor do they slow progression of the disease. Therefore, effective treatment for chemotherapy induced neuropathy would be a major advantage for cancer patients. Benfotiamine (BT) a lipid soluble form of thiamine plays important role in various biological pathways reported beneficial effect in diabetic retinopathy. Erythropoietin (EPO) has recently been considered as a tissue protective cytokine.EPO is reported to protect neurons from ischemia reperfusion-induced injury, metabolic stress, HIV-induced damage or even mechanical injury such as nerve compression or trauma.Thereforethe present study was undertaken to evaluate the individual and combination effects of BT and EPO in cisplatin induced peripheral neuropathy in rats. PN was induced by Cisplatin - 2mg/kg,i.p. twice weekly for 8 weeks. The degree of protection was determined by measuring electrophysiological properties of sciatic nerve like nerve conduction velocity, behavioralparameters like motor in-coordination, thermal & cold hyperalgesia, grip strength, biochemal parameters like measurement of endogenous antioxidants and histopathological studies.PN was evidenced in Cisplatin control rats and ameliorated with administration of BT (100 mg/kg p.o daily)and EPO (500U/kg i.p. thrice weekly) for 8 weeks by augmenting all the above parameters.T4 exhibited neuroprotective activity, which would be attributed to its activity as neurotrophic effect.

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