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.

Acetaldehyde↗

PubMedDate not supplied

Thiram-induced disturbance of microsomal phospholipid bioformation and phospholipid fatty acid pattern.

In rats, a single oral dose of 30 mg or 1 g thiram per kilogram produced a significant prolongation of the hexobarbital sleeping time or zoxazolamine paralysis time, respectively, a depression of hepatic microsomal O-demethylation of p-nitroanisole to p-nitrophenol, and a decrease in the microsomal cytochrome P-450 content. In addition, incorporation of 14C activity from glucose, glycerol, and palmitic acid into phospholipids (PLs) decreased in most of the components, showing a compensatory increase in only a few of them. Fatty acid (FA) concentrations in phosphatidylcholine (PC) or phosphatidylethanolamine (PE) molecules were increased or decreased from one FA class to the other. This alteration of the FA concentrations in PC and PE, respectively, was virtually exclusively in position 2 of the two PL molecules. The total content of saturated FAs in PC and PE was significantly decreased only after 1 g/kg thiram; this was associated with an increase in total unsaturated FAs. The multiple changes in the bioformation and composition of microsomal membrane PLs suggest a disturbance of the monooxygenase system. It is conceivable that there is an interrelationship between the observed impairment and the inhibitory effect of thiram on the microsomal monoxygenases (MMs).

Animals↗

PubMedDate not supplied

Behaviour of epoxide hydrolase, glutathione S-transferase, alcohol dehydrogenase, and aldehyde dehydrogenase, respectively, under the influence of carbon disulfide studies with rats in vivo and in vitro.

High concentrations of carbon disulfide in rat liver preparations do not change the activities of glutathione S-transferase, alcohol dehydrogenase, or aldehyde dehydrogenase and exert a slightly augmenting effect (not significant) on the activity of epoxide hydrolase. Carbon disulfide administered orally to rats in a high dose enhances the activity of hepatic epoxide hydrolase slightly (not significant), but has no influence on hepatic glutathione S-transferase in the cytosol and in microsomes. The results obtained in vitro and in vivo permit the assumption that occupational CS2-exposure does not appreciably inhibit the activities of epoxide hydrolase and glutathione S-transferase. The in-vitro findings with alcohol dehydrogenase and aldehyde dehydrogenase support the view held in the literature that the alcohol intolerance observed after occupational CS2-exposure ("Antabuse syndrome"-like reaction) is due to an inhibition of aldehyde dehydrogenase by CS2-metabolites of the thiocarbamate type.

Alcohol Oxidoreductases↗