EFFECTS OF GAMMA-GLUTAMYLCYSTEINE ETHYL-ESTER IN CISPLATIN-INDUCED CHANGES IN PROSTANOID CONCENTRATIONS IN RAT GASTRIC AND COLONIC MUCOSA

We evaluated changes in gastric and colonic mucosal prostanoid content s in rats treated with cisplatin. We also determined effects of gamma- glutamylcysteine ethyl ester (GCE), a pro-drug of glutathione, on cisp latin-induced changes in prostanoid concentrations. Rats were divided into three groups-the control: 0.5 mi of physiological saline was admi nistered intraperitoneally (i.D.); the cisplatin group: 0.5 mi of cisp latin, 10 mg/kg, was administered i.p.; the GCE + cisplatin group: GCE , 30 min before cisplatin injection. In each group, rat gastric and co lonic mucosa were isolated and their prostanoid concentrations were de termined using highperformance liquid chromatography. 6-Keto-PGF(1 alp ha), PGF(2 alpha), PGE(2) were detected in gastric mucosa. In addition to these prostaglandins (PGs), thromboxane (TX) B-2, was also detecte d in the colonic mucosa. In the cisplatin group, gastric mucosal 6-ket o-PGF(1 alpha) concentration decreased significantly 24 h after admini stration, while PGE(2) and PGD(2) concentrations were increased signif icantly after 12 and 24 h, respectively. In colonic mucosa, cisplatin increased PGE(2) and PGD(2) concentrations, while it decreased TXB2, c oncentration. 6-Keto-PGF(1 alpha), concentration was not affected by c isplatin in colonic mucosa. GCE canceled out these changes in prostano id concentrations in both gastric and colonic mucosa. Changes in prost anoid concentrations might be implicated in the adverse gastrointestin al effects of cisplatin, and clinical application of GCE could be expe cted.