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.
D000818:Animals; D002531:Cerebellum / Q000187:drug effects* / Q000201:enzymology; D004347:Drug Interactions; D005696:Galactosidases / Q000378:metabolism*; D005966:Glucuronidase / Q000378:metabolism*; D007700:Kinetics; D008920:Misonidazole / Q000633:toxicity*; D009593:Nitroimidazoles / Q000633:toxicity*; D010525:Peripheral Nerves / Q000187:drug effects* / Q000201:enzymology; D051381:Rats; D011919:Rats, Inbred Strains; D013831:Thiamine / Q000494:pharmacology*; D013835:Thiamine Pyrophosphate / Q000494:pharmacology*; D014810:Vitamin E / Q000494:pharmacology*; D001616:beta-Galactosidase / Q000378:metabolism*
D009593:Nitroimidazoles; D014810:Vitamin E; D008920:Misonidazole; D005696:Galactosidases; D001616:beta-Galactosidase; D005966:Glucuronidase; D013835:Thiamine Pyrophosphate; D013831:Thiamine