Published in Cancer Detection and Prevention 1998; 22(2):153-160.

Effects of Gamma-Glutamylcysteine Ethyl Ester in cisplatin-Induced Changes in Prostanoid Concentrations in Rat Gastric and Colonic Mucosa

H Goto, MDa, K Tachi, MDa, T Arisawa, MDa, Y Niwa, MDa, T Hayakawa, MDa, and S Sugiyama, MDb

aDepartment of Internal Medicine, University of Nagoya, Tsuruma, Showa-ku, Nagoya, Japan; and bDepartment of Clinical Chemistry, Institute of Applied Biochemistry, Mitake, Gifu, Japan

Address all correspondence and reprint requests to: Hidemi Goto, M.D., Department of Internal Medicine, Faculty of Medicine. University of Nagoya. Tsaruma, Showa-ku, Nagoya 466, Japan.

ABSTRACT: We evaluated changes in gastric and colonic mucosal prostanoid contents in rats treated with cisplatin. We also determined effects of gamma-glutamylcysteine ethyl ester (GCE), a pro-drug of glutathione, on cisplatin-induced changes in prostanoid concentrations. Rats were divided into three groups-the control: 0.5 ml of physiological saline was administered intraperitoneally (i.p.); the cisplatin group: 0.5 ml of cisplatin, 10 mg/kg, was administered i.p.; the GCE + cisplatin group: GCE, 30 min before cisplatin injection. In each group, rat gastric and colonic mucosa were isolated and their prostanoid concentrations were determined using high-performance liquid chromatography. 6-Keto-PGF1alpha, PGF2alpha, PGE2 were detected in gastric mucosa. In addition to these prostaglandins (PGs), thromboxane (TX) B2 was also detected in the colonic mucosa. In the cisplatin group, gastric mucosal 6-keto-PGF1alpha concentration decreased significantly 24 h after administration, while PGE2 and PGD2 concentrations were increased significantly after 12 and 24 h, respectively. In colonic mucosa, cisplatin increased PGE2 and PGD2 concentrations, while it decreased TXB2 concentration. 6-Keto-PGF1alpha concentration was not affected by cisplatin in colonic mucosa. GCE canceled out these changes in prostanoid concentrations in both gastric and colonic mucosa. Changes in prostanoid concentrations might be implicated in the adverse gastrointestinal effects of cisplatin, and clinical application of GCE could be expected.

KEY WORDS: adverse effects, cisplatin, gastrointestinal tract, gamma-glutamylcysteine ethyl ester, prostanoids.