Effects of 5-fluorouracil on the thiamin status of adult female rats.
The effect of 5-fluorouracil on the thiamin status of normal female adult rats has been investigated. Pre-treatment of the animals with the cytotoxic drug daily for 3 successive days resulted in a significant decrease in hepatic concentrations of thiamin concomitant with a decrease in thiamin-dependent transketolase enzyme activity and an increase in thiamin-pyrophosphate-(TPP-)stimulating effect in whole blood when compared with those of pair-fed control animals. The TPP effect of transketolase enzyme activity was also increased by 5-fluorouracil in vitro. Furthermore, the treatment with 5-fluorouracil resulted in decreased liver and spleen concentrations without affecting the urinary excretory levels of thiamin in animals supplemented with large doses of the vitamin. Giving a dose comparable to a human therapeutic dose caused a similar increase in the TPP effect. These results indicate that treatment with 5-fluorouracil may be associated with thiamin deficiency by increasing either the utilization or the breakdown of thiamin.
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D005260:Female; D005472:Fluorouracil / Q000494:pharmacology*; D008099:Liver / Q000378:metabolism; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D013154:Spleen / Q000378:metabolism; D013831:Thiamine / Q000008:administration & dosage / Q000378:metabolism* / Q000652:urine; D013835:Thiamine Pyrophosphate / Q000494:pharmacology; D014174:Transketolase / Q000097:blood*
D014174:Transketolase; D013835:Thiamine Pyrophosphate; D005472:Fluorouracil; D013831:Thiamine