Protection against misonidazole-induced neuropathy in rats: a biochemical assessment

A biochemical method for assessing the chemically induced neurotoxicity of misonidazole (MISO) in the rat has been used to assess whether the concurrent administration of thiamine, thiamine pyrophosphate (TPP) or vitamin E (Vit.E) could afford protection against the neurotoxic side effects of the drug. The tissues analysed were distal sections of the sciatic/posterior tibial nerve (SPTN), trigeminal ganglia and cerebellum. MISO was administered i.p. to Wistar rats at a dose of 400 mg/kg per day for 7 consecutive days to produce the maximal measurable enzyme changes after 4 weeks. The concurrent i.p. and i.m. dosing of thiamine (0.1-100 mg/kg) for 15 consecutive days did not abate the subsequent PNS and CNS enzyme changes. However, with concurrent i.m. dosing of 1.0 mg/kg TPP or p.o. dosing of vitamin E (30 mg/kg) afforded some protection against both the PNS and CNS MISO-induced neurotoxic side effects as measured biochemically.