Inducers of cytochrome P450 2E1 enhance methotrexate-induced hepatocytotoxicity

Objectives: The regular consumption of alcohol in moderate amounts (defined in North America as up to 2 drinks per day for men and 1 drink per day for females) has been recognized in the last decade as a negative risk factor for atherosclerosis and its clinical sequelae: coronary heart disease (CHD), ischemic stroke, and peripheral vascular disease. Mortality and morbidity attributable to CHD are 40–60% lower in moderate drinkers than among abstainers. Among the mechanisms accounting for these reductions, increased circulating concentrations of HDL-cholesterol and inhibition of blood coagulation appear to be paramount. Additional benefits are, in certain beverages, conferred by the presence of constituents other than alcohol (e.g., flavonoids and hydroxystilbenes), which prevent oxidative damage, free radical formation, and elements of the inflammatory response. Conclusions: A number of other diseases appear to be beneficially modulated by moderate alcohol consumption based on epidemiologic surveys and, in some instances, experimental evidence. These include duodenal ulcer, gallstones, enteric infections, rheumatoid arthritis, osteoporosis, and diabetes mellitus (type II). Compared with abstainers, moderate drinkers exhibit improved mental status characterized by decreased stress and depression, lower absenteeism from work, and decreased incidence of dementia (including Alzheimer’s disease). Although limits of safe drinking have been conservatively defined, it is regrettable that political considerations are hampering the clinical application of this knowledge and its dissemination to the lay public.