Protective effect of vitamin A against the methotrexate-induced damage to small intestine: a study on the crypt cells.
Vitamin A (VA) protects the small intestine from the methotrexate (MTX)-induced damage. The in vivo effects of MTX and/or VA on crypt cells of small intestine were investigated using rats orally administered MTX (15 mg/kg body weight) and/or VA (5,000 IU/kg body weight). The thymidine kinase activity of crypt cells separated from villus cells of small intestine of MTX plus VA-treated rats was lower than that from control rats but higher than that from MTX-treated rats. VA-treated rats showed almost the same activity of thymidine kinase as control rats. The amounts of the end products, adenosine monophosphate (AMP) and guanosine monophosphate (GMP), contained in crypt cells of treated rats were determined to investigate the in vivo effects of MTX and/or VA on de novo purine synthesis. MTX treatment significantly decreased the amounts of both AMP and GMP but both amounts were not affected by MTX plus VA treatment. Treatment with VA alone appeared to increase their amounts slightly. Thus, although the oral administration of MTX to rats inhibited DNA synthesis in crypt cells, VA coadministration protected the salvage pathway of pyrimidine synthesis and the de novo purine synthesis in crypt cells.
Kosakai
Y
Y
Department of Biopharmaceutics, Tokyo College of Pharmacy, Japan.
Horie
T
T
Awazu
S
S
D000818:Animals; D007410:Intestinal Diseases / Q000139:chemically induced / Q000517:prevention & control*; D007421:Intestine, Small / Q000166:cytology / Q000187:drug effects*; D008297:Male; D008727:Methotrexate / Q000009:adverse effects*; D011685:Purine Nucleotides / Q000378:metabolism; D011687:Purines / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013937:Thymidine Kinase / Q000378:metabolism; D014801:Vitamin A / Q000627:therapeutic use*
D011685:Purine Nucleotides; D011687:Purines; D014801:Vitamin A; D013937:Thymidine Kinase; D008727:Methotrexate