Ali A T
Department of Medical Pharmacology (31), College of Medicine, King Saud University, Riyadh, Saudi Arabia.
J Pharm Pharmacol. 1995 Sep;47(9):739-43. doi: 10.1111/j.2042-7158.1995.tb06734.x.
The role of endogenous nitric oxide and sulphydryls in gastric protection afforded by sodium cromoglycate against ethanol-induced gastric lesions was studied in rats. Drugs were administered either intraperitoneally (i.p.) or subcutaneously (s.c.) 30, 45 or 60 min before oral administration of ethanol. Administration of cromoglycate before ethanol dose-dependently inhibited ethanol-induced gastric lesions. Pretreatment with NG-nitro-L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide biosynthesis, dose-dependently aggravated gastric lesions and reduced cromoglycate-induced gastric protection. The attenuating effect of L-NAME on gastric protection elicited by cromoglycate was reversible by pretreatment with L-arginine but not by D-arginine. On the other hand, ethanol-induced gastric lesions were found to be associated with a reduction of nonprotein sulphydryl content of glandular stomachs. Pretreatment with cromoglycate prevented non protein sulphydryl depletion and afforded protection. Pretreatment with N-ethylmaleimide, a sulphydryl blocker, caused dose-dependent enhancement of ethanol-induced gastric lesions and further depletion of non protein-sulphydryl. Treatment with N-ethylmaleimide before cromoglycate reduced the gastric protection that was associated with depletion of nonprotein sulphydryls. Furthermore, combined N-ethylmaleimide and L-NAME pretreatment caused a greater aggravation of ethanol-induced gastric lesions and significantly produced a higher reduction of the protective effects of cromoglycate. However, pretreatment with L-arginine only partially restored the protective effects of cromoglycate. These results suggest that the protective effects of cromoglycate may be dependent on the maintenance of a critical level of both endogenous nitric oxide and nonprotein sulphydryls in the gastric mucosa.
在大鼠中研究了内源性一氧化氮和巯基在色甘酸钠对乙醇诱导的胃损伤的胃保护作用中的作用。在口服乙醇前30、45或60分钟通过腹腔内（i.p.）或皮下（s.c.）给予药物。在给予乙醇前给予色甘酸钠剂量依赖性地抑制乙醇诱导的胃损伤。用一氧化氮生物合成抑制剂NG-硝基-L-精氨酸甲酯（L-NAME）预处理剂量依赖性地加重胃损伤并降低色甘酸钠诱导的胃保护作用。L-NAME对色甘酸钠引起的胃保护作用的减弱效应可通过L-精氨酸预处理逆转，但不能通过D-精氨酸逆转。另一方面，发现乙醇诱导的胃损伤与腺胃非蛋白巯基含量的降低有关。用色甘酸钠预处理可防止非蛋白巯基耗竭并提供保护。用巯基阻断剂N-乙基马来酰亚胺预处理导致乙醇诱导的胃损伤剂量依赖性增强以及非蛋白巯基的进一步耗竭。在色甘酸钠之前用N-乙基马来酰亚胺处理降低了与非蛋白巯基耗竭相关的胃保护作用。此外，联合N-乙基马来酰亚胺和L-NAME预处理导致乙醇诱导的胃损伤更严重加剧，并显著降低色甘酸钠的保护作用。然而，用L-精氨酸预处理仅部分恢复了色甘酸钠的保护作用。这些结果表明，色甘酸钠的保护作用可能取决于胃粘膜中内源性一氧化氮和非蛋白巯基的临界水平的维持。
