Ferrous sulfate combined with ascorbic acid does not significantly reduce acetaldehyde accumulation in the blood of alcoholized rats treated with disulfiram or betalactam antibiotics.
Adult female SPF Sprague-Dawley rats treated orally by gavage with disulfiram (1 g/kg b.wt.) or betalactam antibiotics (3.38 mmol/kg b.wt.) with a 1-methyltetrazole-5-thiol side chain (cefmenoxime, latamoxef, cefotetan, cefoperazone, cefamandole) produced a marked, statistically significant rise of acetaldehyde in the blood 1 and 3 hr following IP administration of ethanol [2 g/kg b.wt., 20% (g/v) solution]. This accumulation of blood acetaldehyde remained unchanged or was reduced only very slightly by a mixture of iron sulfate [Fe(II)SO4.7H2O, 2.64 mg/kg b.wt.] and ascorbic acid (6.67 mg/kg b.wt.) injected intravenously. This slight decrease is considered to be due to a formation of a complex between ferrous sulfate and agents (disulfiram and the betalactam antibiotics as well as their metabolites) producing acetaldehyde by inhibition of acetaldehyde metabolizing enzymes. A possible coaction of ascorbic acid cannot be explained satisfactorily; ascorbic acid may support cellular redox potentials. The combination of ferrous sulfate and ascorbic acid was used for examination since both chemicals are recommended to reduce adverse symptoms of an ethanol incompatibility reaction in the course of a therapy with the mentioned antibiotics or disulfiram. Since acetaldehyde augmentation in the blood is regarded as a cause of complaints and because the acetaldehyde rise was not depressed significantly by ferrous sulfate and ascorbic acid it can be concluded that these two agents are not potent enough for a rational therapy of ethanol incompatibility symptoms initiated by the investigated drugs.
Freundt
K J
KJ
Institute of Pharmacology and Toxicology, Faculty of Clinical Medicine Mannheim, University of Heidelberg, F.R.G.
Heiler
C
C
Schreiner
E
E
D000079:Acetaldehyde / Q000097:blood*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000009:adverse effects / Q000494:pharmacology*; D001205:Ascorbic Acid / Q000494:pharmacology* / Q000627:therapeutic use; D004221:Disulfiram / Q000009:adverse effects / Q000494:pharmacology*; D004347:Drug Interactions; D000431:Ethanol / Q000009:adverse effects / Q000494:pharmacology*; D005260:Female; D005296:Ferrous Compounds / Q000494:pharmacology* / Q000627:therapeutic use; D007769:Lactams; D051381:Rats; D011919:Rats, Inbred Strains
D000900:Anti-Bacterial Agents; D005296:Ferrous Compounds; D007769:Lactams; C020748:ferrous sulfate; D000431:Ethanol; D000079:Acetaldehyde; D001205:Ascorbic Acid; D004221:Disulfiram