Gastric and intestinal ethanol toxicity in the rat. Effect on glutathione level and role of alcohol and acetaldehyde metabolisms.
OBJECTIVE
This study investigated the dose- and time-dependent effect of ethanol on gastric and intestinal glutathione and protein oxidative state in the rat.


METHODS
Rats received 1 or 4 g/kg of 25% ethanol solution orally or isocaloric glucose. Some rats received diethylmaleate, cimetidine or cyanamide before ethanol (1 g/kg). Glutathione, carbonyl proteins and histological damage were evaluated in the gastric and intestinal mucosa 6 hours after treatment.


RESULTS
An increase in glutathione was observed 2 to 6 hours after 1 g/kg of ethanol both in the gastric and intestinal mucosa, whereas 4 g/kg decreased glutathione. The rise in glutathione after ethanol was associated with increased levels of its oxidized form; however, the total/oxidized ratio was significantly decreased only in the intestinal tract. Diethylmaleate depleted mucosal glutathione, while the subsequent ingestion of ethanol increased it. Unlike stomach, intestine showed a significant increase in carbonyl proteins and marked histological lesions after ethanol ingestion. Cimetidine and cyanamide inhibited by 50% the activity of alcohol dehydrogenase and by 80% aldehyde dehydrogenase, respectively, in the gastric and intestinal mucosa. Cyanamide significantly enhanced ethanol-induced protein oxidation and mucosal injury in the stomach. No such effect was observed in the intestine.


CONCLUSIONS
The increase of glutathione after ingestion of low amounts of ethanol appears to be an adaptive mechanism against ethanol toxicity. Depletion of glutathione increased protein oxidation and the extent of histological damage in ethanol-treated rats. At gastric level, the effects of ethanol are exaggerated by the inhibition of acetaldehyde metabolism; while intestinal damages appear to be ascribed to ethanol itself.
Altomare
E
E
Department of Internal and Occupational Medicine, University of Bari, Italy.
Grattagliano
I
I
Didonna
D
D
Gentile
A
A
Vendemiale
G
G
D000079:Acetaldehyde / Q000378:metabolism*; D000426:Alcohol Dehydrogenase / Q000187:drug effects / Q000378:metabolism; D000444:Aldehyde Dehydrogenase / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology; D002927:Cimetidine / Q000494:pharmacology; D003484:Cyanamide / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000633:toxicity*; D005500:Follow-Up Studies; D005753:Gastric Mucosa / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D005978:Glutathione / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008298:Maleates / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D000897:Anti-Ulcer Agents; D008298:Maleates; D000431:Ethanol; D003484:Cyanamide; D002927:Cimetidine; D000426:Alcohol Dehydrogenase; D000444:Aldehyde Dehydrogenase; C014476:diethyl maleate; D005978:Glutathione; D000079:Acetaldehyde