Preconditioning with subneurotoxic allyl nitrile: protection against allyl nitrile neurotoxicity.
High-dose cruciferous allyl nitrile can induce behavioral abnormalities in rodents, while repeated exposure to allyl nitrile at subneurotoxic levels can increase phase 2 detoxification enzymes in many tissues, although the brain has not been investigated yet. In the present study, we examined the effect of 5 days repeated exposure to subneurotoxic allyl nitrile (0-400 micromol/kg/day) on the brain. Elevated glutathione S-transferase activity was recorded in the striatum, hippocampus, medulla oblongata plus pons, and cortex. Enhancement of quinone reductase activity was observed in the medulla oblongata plus pons, hippocampus, and cortex. In the medulla oblongata plus pons, elevated glutathione levels were recorded. Following repeated subneurotoxic allyl nitrile exposure (0-400 micromol/kg/day), mice were administered a high-dose allyl nitrile (1.2 mmol/kg) which alone led to appearance of behavioral abnormalities. Compared with the 0 micromol/kg/day group, animals in the 200 and 400 micromol/kg/day pre-treatment groups exhibited decreased behavioral abnormalities and elevated GABA-positive cell counts in the substantia nigra pars reticulata and the interpeduncular nucleus. These data suggest that repeated exposure to subneurotoxic levels of allyl nitrile can induce phase 2 enzymes in the brain, which together with induction in other tissues, may contribute to protection against allyl nitrile neurotoxicity.
Tanii
H
H
Department of Hygiene, Graduate School of Medical Science, Kanazawa University, 13-1 Takara-Machi, Kanazawa 920-8640, Japan. taniih@med.kanazawa-u.ac.jp
Higashi
T
T
Saijoh
K
K
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000201:enzymology; D002452:Cell Count; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004790:Enzyme Induction / Q000187:drug effects*; D005982:Glutathione Transferase / Q000096:biosynthesis; D007150:Immunohistochemistry; D008297:Male; D050217:Metabolic Detoxication, Phase II / Q000502:physiology; D051379:Mice; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000096:biosynthesis; D009422:Nervous System Diseases / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D009498:Neurotoxins / Q000633:toxicity*; D009570:Nitriles / Q000633:toxicity*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D009498:Neurotoxins; D009570:Nitriles; C015660:allyl cyanide; D005680:gamma-Aminobutyric Acid; D016660:NAD(P)H Dehydrogenase (Quinone); D005982:Glutathione Transferase