Modulation of nitrogen dioxide toxicity by lithium.
The effect of short-term intake of LiCl in drinking fluid on NO2 toxicity was studied in mice as a function of mortality and of specific activities of mouse liver alcohol dehydrogenase (L-ADH) and aldehyde dehydrogenases (L-ALDH). Pretreatment with LiCl for 10 days decreased mortality in mice exposed to 60 to 70 PPM NO2 for 6 hr compared to controls. Pretreatment with LiCl for 10 days under continued exposure to 5 PPM NO2 resulted in a decrease in liver weight compared to control. Lithium treated mice exposed to NO2 showed less gain in body weight than the controls treated with LiCl and exposed to air. The latter group showed an induction of mitochondrial but not cytoplasmic L-ALDH and the NO2 exposure did not alter endogenous L-ALDH from corresponding controls. This induction of mitochondrial ALDH was associated with an increase in both Vmax and the apparent Km. Exposure to NO2 for 10 consecutive days resulted in inhibition of cytoplasmic L-ALDH. The data suggest that Li+ antagonized NO2 toxicity. A possible mechanism for reduction of NO2 toxicity by LiCl may be due to Li+ action on stabilizing cell membranes and/or modifying intercellular pulmonary response to NO2 injury.
D000079:Acetaldehyde / Q000378:metabolism; D000426:Alcohol Dehydrogenase; D000429:Alcohol Oxidoreductases / Q000378:metabolism; D000444:Aldehyde Dehydrogenase / Q000378:metabolism; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D000431:Ethanol / Q000378:metabolism; D005260:Female; D008094:Lithium / Q000494:pharmacology*; D008099:Liver / Q000201:enzymology; D008297:Male; D051379:Mice; D008930:Mitochondria, Liver / Q000201:enzymology; D009585:Nitrogen Dioxide / Q000037:antagonists & inhibitors / Q000633:toxicity*; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains
D000431:Ethanol; D008094:Lithium; D000429:Alcohol Oxidoreductases; D000426:Alcohol Dehydrogenase; D000444:Aldehyde Dehydrogenase; D000079:Acetaldehyde; D009585:Nitrogen Dioxide