BIOCHEMICAL CONSEQUENCES OF 5-FLUOROURACIL GASTROINTESTINAL TOXICITY IN RATS - EFFECT OF HIGH-DOSE URIDINE

Selective protection of the normal host tissues from the toxic effects of anticancer agents would allow the use of higher, probably more eff ective, doses of the drugs. It has been demonstrated that delayed high -dose uridine administration after 5-fluorouracil decreases the extent of myelosuppression and causes faster regeneration of the bone marrow . We studied the biochemical consequences of the gastrointestinal toxi city caused by 5-fluorouracil and the potential of high-dose uridine t reatment to influence these adverse effects. 5-Fluorouracil caused dos e-related decreases in the biochemical parameters (thymidine kinase, s ucrase, maltase, alkaline phosphatase) selected as early markers of th e impaired. metabolic activity of the intestinal mucosa. The nadir of the biochemical changes was reached between 24 h and 72 h after 5-fluo rouracil treatment, and complete regeneration of the mucosa took 6-7 d ays. Delayed high-dose uridine administration failed to mitigate the s everity of the gastrointestinal damage that ensued after 5-fluorouraci l treatment, but caused significantly earlier regeneration of the muco sa.