Ethanol has differential effects on rat neuron and thymocyte reactive oxygen species levels and cell viability.
In rat thymocytes and cerebellar granule cells, reactive oxygen species (ROS) levels were increased and cell viability was decreased as a result of exposure to ethanol (up to 0.4%). Thymocytes showed larger increases in ROS levels, but neurons showed more pronounced decreases in cell viability. These parameters in neurons were relatively unaffected when the cells were incubated with ethanol in the presence of inhibitors of alcohol-oxidizing enzymes, but in thymocytes, the presence of diallyl sulfide (an inhibitor of alcohol-inducible cytochrome P450, CYP2E1) or 4-methylpyrazole (an inhibitor of CYP2E1 and alcohol dehydrogenase) caused decreases in ROS production from ethanol. In both cell types, the presence of 3-aminotriazole (an inhibitor of catalase) did not decrease ROS production from ethanol. These studies show that the cytotoxic effects of ethanol in neurons may not be the result of oxidative metabolism of ethanol, whereas in thymocytes, the cytotoxic effect of ethanol is principally a result of its oxidative metabolism.
Huentelman
M J
MJ
Department of Chemistry and Biochemistry, Ohio University, Athens 45701, USA.
Peters
C M
CM
Ervine
W E
WE
Polutnik
S M
SM
Johnson
P
P
D000426:Alcohol Dehydrogenase / Q000037:antagonists & inhibitors; D000498:Allyl Compounds / Q000494:pharmacology; D000640:Amitrole / Q000494:pharmacology; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D002374:Catalase / Q000037:antagonists & inhibitors; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology / Q000187:drug effects; D065691:Cytochrome P-450 CYP2E1 Inhibitors; D000431:Ethanol / Q000494:pharmacology*; D005260:Female; D000077604:Fomepizole; D005609:Free Radicals / Q000378:metabolism; D008297:Male; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013440:Sulfides / Q000494:pharmacology; D013950:Thymus Gland / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism
D000498:Allyl Compounds; D000975:Antioxidants; D065691:Cytochrome P-450 CYP2E1 Inhibitors; D005609:Free Radicals; D011720:Pyrazoles; D017382:Reactive Oxygen Species; D013440:Sulfides; D000431:Ethanol; C038491:allyl sulfide; D000077604:Fomepizole; D000426:Alcohol Dehydrogenase; D002374:Catalase; D000640:Amitrole