Role of sulfhydryls in mucosal injury caused by ethanol: relation to microvascular permeability, gastric motility and cytoprotection.
The relationship between gastric mucosal glutathione (GSH) levels, vascular permeability, gastric motility and mucosal injury caused by ethanol was investigated in rats. Oral administration of 50% ethanol (1 ml) produced elongated reddish bands of lesions in the mucosa with a significant reduction of GSH levels and increase of microvascular permeability. These lesions were significantly inhibited by pretreatment with s.c. administered diethylmaleate (DEM: 1 ml/kg), cysteamine (100 mg/kg) and 16, 16-dimethyl prostaglandin E2 (dmPGE2, 10 micrograms/kg) but worsened markedly by N-ethylmaleimide (NEM: 10 mg/kg). Irrespective of whether the animals were treated with 50% ethanol or not, the mucosal GSH levels were significantly decreased or increased, respectively, by DEM or cysteamine, and were not affected by both NEM and dmPGE2. NEM significantly enhanced the vascular permeability in the absence or presence of ethanol (greater than 10%), whereas other agents significantly inhibited only the increased vascular permeability caused by ethanol. On the other hand, gastric motility was potently and persistently inhibited by either DEM, cysteamine or dmPGE2 at the doses which prevented ethanol-induced mucosal injury, whereas NEM had no effect on the motility. These results suggest that 1) the mucosal GSH levels do not relate directly to either development or prevention of ethanol-induced gastric injury, 2) potentiation by NEM of the mucosal injury may be accounted for by its enhancement of the vascular permeability and 3) inhibition of gastric motility may be associated with prevention of mucosal lesions.
Takeuchi
K
K
Department of Applied Pharmacology, Kyoto Pharmaceutical University, Japan.
Okada
M
M
Niida
H
H
Okabe
S
S
D015064:16,16-Dimethylprostaglandin E2 / Q000494:pharmacology; D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects*; D003543:Cysteamine / Q000494:pharmacology; D000431:Ethanol / Q000633:toxicity*; D005033:Ethylmaleimide / Q000494:pharmacology; D005753:Gastric Mucosa / Q000032:analysis / Q000187:drug effects*; D005769:Gastrointestinal Motility / Q000187:drug effects*; D005978:Glutathione / Q000032:analysis / Q000502:physiology*; D008297:Male; D008298:Maleates / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
D008298:Maleates; D000431:Ethanol; D003543:Cysteamine; C014476:diethyl maleate; D005978:Glutathione; D015064:16,16-Dimethylprostaglandin E2; D005033:Ethylmaleimide