Effects of antineoplastics, antibiotics and antidiabetics on acetaldehyde metabolism after alcohol ingestion.
The main purpose of this study was to evaluate the inhibitory effects of 5-fluorouracil antineoplastics, cephem antibiotics containing the methyltetrazolylthiol (MTT) group and antidiabetics on aldehyde dehydrogenase (ALDH) activity in vivo and in vitro. In in vivo experiments, rats were given a 100 mg/kg dose of drugs (10 mg/kg for glibenclamide) orally or intraperitoneally. When each drug was administered singly immediately after an oral administration of 1.5 g/kg ethanol, only carmofur, an antineoplastic, produced marked increases in blood acetaldehyde concentrations. This action was also noted when ethanol was ingested 15 h after administration. The remaining drugs did not increase blood acetaldehyde concentrations. When rats were treated with carmofur at 12 h intervals for 3 consecutive days and were given 1.5 g/kg ethanol after the final treatment, blood acetaldehyde concentrations were elevated more significantly than with a single administration of carmofur. Furthermore, daily administration of cephem antibiotics containing the MTT group, latamoxef, cefamandole, cefoperazone and cefbuperazone, significantly increased blood acetaldehyde concentrations. Daily administration of sulfonylurea antidiabetics, chlorpropamide and acetohexamide, slightly increased blood acetaldehyde concentrations. Drugs causing increases in blood acetaldehyde concentrations when administration was combined with ethanol ingestion also inhibited ALDH activity in vitro. The results of the in vitro experiments roughly correlated with those of the in vivo experiments. The inhibitory effects of drugs on ALDH activity were in the following order: carmofur >> cephem antibiotics containing the MTT group > sulfonylurea antidiabetics.
Kan
S
S
Department of Legal Medicine, Okayama University Medical School, Japan.
Moriya
F
F
Ishizu
H
H
D000079:Acetaldehyde / Q000097:blood / Q000378:metabolism*; D000284:Administration, Oral; D000428:Alcohol Drinking / Q000097:blood / Q000378:metabolism*; D000444:Aldehyde Dehydrogenase / Q000037:antagonists & inhibitors; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage*; D004334:Drug Administration Schedule; D005472:Fluorouracil / Q000008:administration & dosage*; D007004:Hypoglycemic Agents / Q000008:administration & dosage*; D007274:Injections, Intraperitoneal; D007441:Intubation, Gastrointestinal; D007769:Lactams; D008297:Male; D051381:Rats; D017208:Rats, Wistar
D000900:Anti-Bacterial Agents; D007004:Hypoglycemic Agents; D007769:Lactams; D000444:Aldehyde Dehydrogenase; D000079:Acetaldehyde; D005472:Fluorouracil