Amelioration of methotrexate-induced malabsorption by vitamin A. 1997

J Yamamoto, and T Horie, and S Awazu
Department of Biopharmaceutics, Tokyo University of Pharmacy and Life Science, Japan.

Methotrexate (MTX) induces damage to the small intestine, resulting in malabsorption and diarrhea. We found that the coadministration of vitamin A (VA) with MTX protected the small intestine from MTX-induced damage. In this study, the permeability of D-glucose, D-xylose and L-leucine through the small intestine of rats treated with MTX and/or VA was studied using everted segments of small intestine. MTX treatment decreased permeability and VA coadministration prevented the decrease. The transport of D-glucose in the small intestine of MTX plus VA- and VA-treated rats and of control rats followed Michaelis-Menten kinetics, in contrast to the transport kinetics in MTX-treated rats. The pharmacokinetics of orally administered [14C]-D-glucose in control rats and MTX- and/or VA-treated rats was also studied. The bioavailability of D-glucose in MTX-treated rats was lower than in the other three groups. VA coadministration improved the bioavailability of D-glucose. Thus, it seems likely that VA ameliorates MTX-induced malabsorption.

UI MeSH Term Description Entries
D007408 Intestinal Absorption Uptake of substances through the lining of the INTESTINES. Absorption, Intestinal
D007421 Intestine, Small The portion of the GASTROINTESTINAL TRACT between the PYLORUS of the STOMACH and the ILEOCECAL VALVE of the LARGE INTESTINE. It is divisible into three portions: the DUODENUM, the JEJUNUM, and the ILEUM. Small Intestine,Intestines, Small,Small Intestines
D008286 Malabsorption Syndromes General term for a group of MALNUTRITION syndromes caused by failure of normal INTESTINAL ABSORPTION of nutrients. Malabsorption Syndrome,Syndrome, Malabsorption,Syndromes, Malabsorption
D008727 Methotrexate An antineoplastic antimetabolite with immunosuppressant properties. It is an inhibitor of TETRAHYDROFOLATE DEHYDROGENASE and prevents the formation of tetrahydrofolate, necessary for synthesis of thymidylate, an essential component of DNA. Amethopterin,Methotrexate Hydrate,Methotrexate Sodium,Methotrexate, (D)-Isomer,Methotrexate, (DL)-Isomer,Methotrexate, Dicesium Salt,Methotrexate, Disodium Salt,Methotrexate, Sodium Salt,Mexate,Dicesium Salt Methotrexate,Hydrate, Methotrexate,Sodium, Methotrexate
D005947 Glucose A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. Dextrose,Anhydrous Dextrose,D-Glucose,Glucose Monohydrate,Glucose, (DL)-Isomer,Glucose, (alpha-D)-Isomer,Glucose, (beta-D)-Isomer,D Glucose,Dextrose, Anhydrous,Monohydrate, Glucose
D000284 Administration, Oral The giving of drugs, chemicals, or other substances by mouth. Drug Administration, Oral,Administration, Oral Drug,Oral Administration,Oral Drug Administration,Administrations, Oral,Administrations, Oral Drug,Drug Administrations, Oral,Oral Administrations,Oral Drug Administrations
D000596 Amino Acids Organic compounds that generally contain an amino (-NH2) and a carboxyl (-COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. Amino Acid,Acid, Amino,Acids, Amino
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D000964 Antimetabolites, Antineoplastic Antimetabolites that are useful in cancer chemotherapy. Antineoplastic Antimetabolites
D014801 Vitamin A Retinol and derivatives of retinol that play an essential role in metabolic functioning of the retina, the growth of and differentiation of epithelial tissue, the growth of bone, reproduction, and the immune response. Dietary vitamin A is derived from a variety of CAROTENOIDS found in plants. It is enriched in the liver, egg yolks, and the fat component of dairy products. Retinol,11-cis-Retinol,3,7-dimethyl-9-(2,6,6-trimethyl-1-cyclohexen-1-yl)-2,4,6,8-nonatetraen-1-ol, (all-E)-Isomer,All-Trans-Retinol,Aquasol A,Vitamin A1,All Trans Retinol

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