Misonidazole neurotoxicity in mice decreased by administration with pyridoxine

Journal Article · Sat Oct 01 04:00:00 EDT 1983 · Int. J. Radiat. Oncol., Biol. Phys.; (United States)

DOI:https://doi.org/10.1016/0360-3016(83)90326-7· OSTI ID:7013095

Eifel, P J; Brown, D M; Lee, W W; Brown, J M

A series of toxicological and pharmacological experiments was performed to test the hypothesis that alterations of pyridoxine (Vitamin B/sub 6/) metabolism may play an important role in the development of misonidazole (MISO) neurotoxicity. The formation of a Schiff's base between the final reduction product of MISO, 2-amino MISO (NH/sub 2/-MISO), and pyridoxal-HCl in ethanol was demonstrated. Mice receiving daily intraperitoneal injections of MISO suffered significantly less toxicity (as determined by survival, weight gain and neurological tests) when large doses of pyridoxine-HCl (PYR) were delivered concomitantly, and consequently were able to tolerate administration of more than twice as many MISO injections. PYR did not alter the pharmacokinetics of MISO, either when given simultaneously or when given by multiple repeated daily injections prior to MISO. The administration of PYR also did not alter the radiosensitization by MISO in an in vivo-in vitro cloning assay with the EMT6 tumor in BALB/c mice. If depletion or altered metabolism of pyridoxine by reduced metabolites is also responsible for the neurotoxic effects of nitroimidazoles in humans, then concomitant administration of pyridoxine (in doses greater than the molar quantity of NH/sub 2/-MISO formed) should inhibit the development of such symptoms and allow administration of larger doses of MISO than are currently clinically employable.

• Research Organization: Stanford Univ. School of Medicine, CA
• OSTI ID: 7013095
• Journal Information: Int. J. Radiat. Oncol., Biol. Phys.; (United States), Journal Name: Int. J. Radiat. Oncol., Biol. Phys.; (United States) Vol. 9:10; ISSN IOBPD
• Country of Publication: United States
• Language: English

Related Subjects

560152* -- Radiation Effects on Animals-- Animals
560305 -- Chemicals Metabolism & Toxicology-- Vertebrates-- (-1987)
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMALS
ANTINEOPLASTIC DRUGS
AZINES
AZOLES
CELL KILLING
DRUGS
EXPERIMENTAL NEOPLASMS
HETEROCYCLIC COMPOUNDS
HYDROXY COMPOUNDS
IMIDAZOLES
INJECTION
INTAKE
INTRAPERITONEAL INJECTION
MAMMALS
METABOLISM
MICE
MISONIDAZOLE
NERVOUS SYSTEM
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
PHARMACOLOGY
PYRIDINES
PYRIDOXINE
RADIOINDUCTION
RADIOSENSITIVITY EFFECTS
RADIOSENSITIZERS
RODENTS
SURVIVAL CURVES
TOXICITY
VERTEBRATES
VITAMIN B GROUP
VITAMINS