Abstract--To elucidate mechanisms involved in the anti-ulcer action of cetraxate, the effects of this agent on the ulcer index (UI), fibrinolytic activity (FA) and contents of several connective tissue components in ulcer tissue were examined using aspirin and acetic acid ulcers in rats. In aspirin ulcer. cetraxate (100 and 300 mg/kg p.o.), like tranexamic acid (500 mg;'kg p.o.), aminocaproic acid (500 mg/kg p.o.) and gefarnatc (200 mg/ kg p.o.), inhibited both the UI and FA. However, aluminum sucrose sulfate (1000 mg/kg p.o.) was effective only against the UI and L-glutamine (500 mg/kg p.o.) failed to inhibit both parameters. In acetic acid ulcer, following oral, daily x either 5 or 8 administrations, cetraxate (200 and 300 mg/kg), gefarnate (200 mg/kg), aluminum sucrose sulfate (1000 mg/ kg) and L-glutamine (500 mg/kg) were effective on both the U I and FA. Tranexamic acid (500 mg/kg) and s-aminocaproic acid (500 mg/kg) were ineffective on the UI, although both agents inhibited FA. In acetic acid ulcer, cetraxate induced increases in hexosamine and uronic acid, that is, acid rnucopolysaccharides (AMPS), especially chondroitin sulfate A and -C, whereas L-glutamine and aluminum sucrose sulfate resulted in increases in hexosamine and sialic acid, that is, glycoproteins. From these results, cetraxate may mainly accelerate the ulcer healing by increasing AMPS in ulcer tissue. Moreover, the local anti-FA property of this agent may be also beneficial in treating bleeding ulcers.We previously reported that cetraxate, 4'-(2-carboxyethyl)phenyl trans-4-aminomethyl cyclohexanecarboxylate hydrochloride, had marked anti-ulcer effects in various acute and chronic types of experimental gastric ulcers, but only slightly inhibitory effects on aggressive factors such as HCl and pepsin in gastric juice (1). These effects were thereafter confirmed by Hashizume et a]. (2). This compound is chemically a ;3-hydroxyphenyl propionic ester of tranexamic acid and has been shown in vitro to possess more potent antiplasmin action than that seen with tranexamic acid (3).In the present study, we attempted to elucidate the mechanism of the anti-ulcer effect of cetraxate and examined the effects of this compound on the ulcer index (UI) and fibrinolytic activity (FA) in ulcer tissue using aspirin and acetic acid-induced ulcers in rats. Furthermore, we also examined the effects of cetraxate on the contents of several connective tissue com ponents in the rat acetic acid ulcer tissue to determine whether or not this drug has accelera tive actions on ulcer healing by increasing tissue components in that region.
MATEREALS AND METHODS DrugsThe drugs used were as follows: cetraxate (Daiichi Seiyaku), tranexamic acid (Daiichi Seiyaku), aminocaproic acid (Daiichi Seiyaku), gefarnate (gefanil, Sumitomo Kagaku), aluminum sucrose sulfate (ulcerimin, Chugai Seiyaku) and L-glutamine (Kyowa Hakko).Production of f experimental gastric ulcers and drug treatment Aspirin ulcer (acute ulcer) : Female Wistar rats, weighing approx. 180 g, were fasted for 24 hr and ...
