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• 5-Fluorouracil (5-FU), 25mg/kg/day, was intraperitoneally administered to male DONRYU rats for up to 5 consecutive days. Histochemical and histological changes in the small intestine (especially the jejunum) were investigated by using electron microscopy to elucidate the mechanism of 5-FU-induced increase in the leakage of macromolecule into the intestinal lumen. The fibrinolysis of the intestinal tissue was also investigated. Acid and alkaline phosphatase activities were markedly decreased after the three doses of 5-FU and could scarcely be traced after the five doses. Horseradish peroxidase (Hrp)-positive granule cells tended to be increased after the two doses of 5-FU, reached the peak after the three doses and became undemonstrable after the five doses. Tissue plasminogen activator activity was markedly increased after the one dose of 5-FU, tended to be decreased after the three doses and became lower than the control value after the five doses. Tissue injury was still slight after the therr doses of 5-FU and did not become marked until the five doses. Trans-4-aminomethyl-cyclohexan carboxylic acid could not prevent 5-FU-induced tissue injury and increase in the leakage of macromolecules into the jejunal lumen. [dl]-α-Tocopherol nicotinate almost completely inhibited 5-FU-induced histochemical changes and increase in the leakage of macromolecules into the jejunal lumen without changing the cellular metabolism-blocking effect of 5-FU. Our study suggested that 5-FU-induced tissue injury and increase in the leakage of exogenous macromolecules into the jejunal lumen might be associated with the release of enzymes present in the lysosome of the jejunal lamina propria.

著者

• 大塚 幸雄

  東邦大学医学部第1内科

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