Mechanisms involved in aggravation of ethanol-induced gastric mucosal lesions in adrenalectomized rats.
Effects of adrenalectomy (AD) on ethanol-induced gastric injury and prostaglandin (PG) protection on the damage were investigated in rats and compared with those of N-ethylmaleimide (NEM), a sulfhydryl (SH) blocker, and diethyl maleate (DEM), a SH depletor. Oral administration of 100% ethanol (1 ml) induced elongated bands of hemorrhagic lesions in the corpus mucosa of sham operated rats, and these lesions were significantly prevented by 16,16-dimethyl PGE2 (dmPGE2, 10 micrograms/kg, s.c.). AD markedly enhanced the mucosal ulcerogenic responses caused by ethanol and abolished the protective effect of dmPGE2; this agent rather worsened the lesions, which appeared throughout the corpus mucosa. AD by itself enhanced the microvascular permeability in the gastric mucosa without any effect on SH contents. These alterations caused by AD were significantly reverted by hydrocortisone treatment (10 mg/kg/day for 2 weeks, s.c.). On the other hand, a single injection of NEM (10 mg/kg, s.c.) similarly enhanced the vascular permeability, worsened the ethanol-induced lesion, and mitigated the protective effect of dmPGE2 without altering mucosal SH contents, while DEM (1 ml/kg, s.c.) significantly reduced the mucosal SH levels and the lesions. These results suggest that AD worsened the mucosal lesions induced by ethanol, probably by enhancing the microvascular permeability, and this action may be due to a lack of steroid secretion but is not directly related to a mucosal SH deficiency.
Nishiwaki
H
H
Department of Applied Pharmacology, Kyoto Pharmaceutical University, Japan.
Okada
M
M
Hara
N
N
Takeuchi
K
K
Okabe
S
S
D015064:16,16-Dimethylprostaglandin E2 / Q000494:pharmacology; D000315:Adrenalectomy / Q000009:adverse effects*; D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects*; D000431:Ethanol / Q000009:adverse effects*; D005033:Ethylmaleimide / Q000494:pharmacology*; D005753:Gastric Mucosa / Q000032:analysis / Q000187:drug effects / Q000473:pathology*; D006854:Hydrocortisone / Q000494:pharmacology; D008293:Malates / Q000494:pharmacology; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013438:Sulfhydryl Compounds / Q000032:analysis
D008293:Malates; D013438:Sulfhydryl Compounds; D000431:Ethanol; C058705:diethyl malate; D015064:16,16-Dimethylprostaglandin E2; D005033:Ethylmaleimide; D006854:Hydrocortisone