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

Toxicol Lett. 1983 Jun;17(1-2):181-5. doi: 10.1016/0378-4274(83)90055-3.

Abstract

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.

MeSH terms

  • Animals
  • Cerebellum / drug effects*
  • Cerebellum / enzymology
  • Drug Interactions
  • Galactosidases / metabolism*
  • Glucuronidase / metabolism*
  • Kinetics
  • Misonidazole / toxicity*
  • Nitroimidazoles / toxicity*
  • Peripheral Nerves / drug effects*
  • Peripheral Nerves / enzymology
  • Rats
  • Rats, Inbred Strains
  • Thiamine / pharmacology*
  • Thiamine Pyrophosphate / pharmacology*
  • Vitamin E / pharmacology*
  • beta-Galactosidase / metabolism*

Substances

  • Nitroimidazoles
  • Vitamin E
  • Misonidazole
  • Galactosidases
  • beta-Galactosidase
  • Glucuronidase
  • Thiamine Pyrophosphate
  • Thiamine