RT Journal Article SR Electronic T1 Vitamin A protects the small intestine from methotrexate-induced damage in rats. JF Journal of Pharmacology and Experimental Therapeutics JO J Pharmacol Exp Ther FD American Society for Pharmacology and Experimental Therapeutics SP 1278 OP 1284 VO 253 IS 3 A1 K Tsurui A1 Y Kosakai A1 T Horie A1 S Awazu YR 1990 UL http://jpet.aspetjournals.org/content/253/3/1278.abstract AB A protective effect of vitamin A (VA) against cytotoxic antitumor drug-induced damage of rat small intestine was found. Oral administration of methotrexate (MTX) for the small intestinal mucosa of rats resulted in a severe histological change, whereas rats coadministered VA with MTX showed a histological status similar to that of control rats. The p.o. administration of MTX led to a decrease in the amounts of membrane proteins and lipids in rat small intestine and its brush border membrane. When administered p.o. with VA, this decrease failed to occur. The brush border membrane of MTX plus VA-treated rats, when monitored by the fluorescence of cationic safranin O and anionic 8-anilino-1-naphthalenesulfonic acid, was found to resemble that from control rats rather than that from MTX-treated rats. The in vitro permeation of MTX in the small intestine of MTX plus VA-treated rats was enhanced, in contrast with the decrease noted for MTX-treated rats. However, that of untreated rats was not affected by the presence of VA. Thus, VA is unlikely to affect the transport process of MTX directly. When administered p.o. with VA, MTX was absorbed effectively to the same or a slightly greater extent than when administered by itself. Consequently, it has been shown histologically, biochemically, physicochemically and physiologically that VA protects the small intestine from the damage induced by MTX.