Vitamin B12 and folate status in rats after chronic administration of ethanol and acute exposure to nitrous oxide.
The chronic administration of ethanol or brief exposure to nitrous oxide (N2O) decreases the activity of hepatic methionine synthase and disrupts normal metabolic processes that require folate and vitamin B12. This combination of drugs has clinical relevance since alcoholic patients often require surgery and receive N2O as a component of their anesthetic. To assess this clinical problem using a rodent model, rats 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 6 weeks, rats were exposed to 60% N2O/40% O2 for 6 hr. Urinary excretions of formic acid and formiminoglutamic acid (FIGLU) were used as indirect markers of folate status. In both the ethanol-fed and control groups, excretion of formic acid and FIGLU markedly increased the first day after N2O and returned towards background values by the second day after N2O exposure. Ethanol treatment alone decreased methionine synthase activities in liver, but not kidney or brain. Exposure to N2O further decreased methionine synthase activities, and recovery of methionine synthase activity after N2O occurred over a period of 4 days at the same rate in both the ethanol-fed and control groups. Ethanol treatment for 6 weeks combined with acute exposure to N2O did not deplete the rats of vitamin B12 in blood, liver, kidney, or brain. We conclude that in this animal model, chronic treatment with ethanol does not markedly exacerbate the disturbances in folate/vitamin B12 metabolism caused by brief exposure to N2O.
Koblin
D D
DD
Department of Anesthesia, Veterans Administration Medical Center, San Francisco, CA 94121.
Everman
B W
BW
D013766:5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase / Q000037:antagonists & inhibitors / Q000097:blood; D000437:Alcoholism / Q000201:enzymology*; D000818:Animals; D005492:Folic Acid / Q000097:blood*; D005561:Formates / Q000652:urine; D005565:Formiminoglutamic Acid / Q000652:urine; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008297:Male; D009609:Nitrous Oxide / Q000633:toxicity*; D051381:Rats; D011919:Rats, Inbred Strains; D014805:Vitamin B 12 / Q000097:blood*
D005561:Formates; C030544:formic acid; D005565:Formiminoglutamic Acid; D005492:Folic Acid; D013766:5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase; D009609:Nitrous Oxide; D014805:Vitamin B 12