Aging, chronic administration of ethanol, and acute exposure to nitrous oxide: Effects on vitamin B 12 and folate status in rats

Abstract

Elderly patients with alcoholism often require surgery and receive nitrous oxide (N 2O) as a component of their anesthetic. Since aging, ethanol, and N 2O may all perturb folate and/or vitamin B 12 metabolism, we examined the combined influence of these parameters on vitamin B 12/folate status in a rodent model. Aged male Fischer 344 rats (24 months old) were given a liquid ethanol diet (35% of calories as ethanol) and control rats were pair-fed a liquid diet with carbohydrate substituting for the caloric content of ethanol. After receiving liquid diets for 7 weeks, rats were exposed to 60% N 2O/40% O 2 for 6 h. Urinary excretion of formic acid, formiminoglutamic acid (FIGLU), and methylmalonic acid (MMA) were used as indirect markers of folate/vitamin B 12 status. In both the aged ethanol-fed and control groups, excretion of formic acid and FIGLU markedly increased the first day after N 2O exposure and returned towards background values by the second day. No changes occurred in MMA excretion. Exposure to N 2O decreased methionine synthase activities in liver, kidney and brain, and recovery of methionine synthase activities occurred over a period of 4 days in both the aged ethanol-fed and control groups. Ethanol treatment for 7 weeks combined with acute exposure to N 2O did not deplete the aged rats of folate or vitamin B 12 in blood, liver, kidney or brain. Thus, in this animal model, aging, chronic ethanol administration, and acute N 2O exposure did not act synergistically to produce prolonged and severe disturbances in folate and vitamin B 12 metabolism.