ALTERATION OF SMALL-INTESTINAL ABSORPTION OF SACCHARIDES IN CIS-DIAMMINEDICHLOROPLATINUM-ADMINISTERED MICE

The effect of cis-diamminedichloroplatinum (DDP) on small intestinal a bsorption of saccharides, and the protective effect of N-p-hydroxymeth ylbenzyl-D-glucamine dithiocarbamate (HBGD) on DDP-induced intestinal toxicity were studied. The small intestinal absorption of D-glucose an d D-galactose, which are actively absorbed, decreased 2 days after DDP administration. The activity of Na+,K+-ATPase in the intestinal tissu e was not inhibited by DDP administration. The small intestinal absorp tion of maltose and sucrose decreased 2 and 4 days after DDP administr ation, The activities of maltase and sucrase in the intestinal mucosa decreased after DDP administration, but these enzyme activities in con trol mice were not inhibited by DDP in the in vitro experiments. A sca nning electron micrograph of the jejunum after DDP showed damage in th e villi. These results indicate that the inhibitory effect of DDP on t he small intestinal absorption of saccharides results from the DDP-ind uced mucosal damage. Treatment with HBGD (1 mmol/kg) 5 min after DDP i njection prevented the decreases in the intestinal absorption of D-glu cose, D-galactose, maltose, and sucrose. Platinum (Pt) concentrations in the small intestine after DDP administration decreased following HB GD treatment. Biliary and urinary excretions of Pt after DDP administr ation were remarkably increased by HBGD treatment. These results indic ate that the administration of DDP to mice causes the decrease in the intestinal absorption of saccharides, and that HBGD can effectively re move Pt from the intestine through biliary and urinary excretions, res ulting in protection against the intestinal toxicity induced by DDP.