Docosahexaenoic acid exhibits a potent protection of small intestine from methotrexate-induced damage in mice

Oral administration of methotrexate (MTX) to mice causes the damage of small intestine. The permeability of poorly absorbable compound fluorescein isothiocyanate (FITC)-labeled dextran (average molecular weight, 4,400) through the small intestine was studied in vitro using everted segments of the sm...

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Bibliographic Details
Published in:Life sciences (1973) 1998, Vol.62 (15), p.1333-1338
Main Authors: Horie, Toshiharu, Nakamaru, Michihiko, Masubuchi, Yasuhiro
Format: Article
Language:English
Subjects:
Animals
Antimetabolites, Antineoplastic - toxicity
Body Weight - drug effects
Dextrans - pharmacokinetics
docosahexaenoic acid
Docosahexaenoic Acids - therapeutic use
Dose-Response Relationship, Drug
Fluorescein-5-isothiocyanate - analogs & derivatives
Fluorescein-5-isothiocyanate - pharmacokinetics
Intestinal Absorption - drug effects
Intestinal Diseases - chemically induced
Intestinal Diseases - metabolism
Intestinal Diseases - prevention & control
Intestine, Small - drug effects
Intestine, Small - metabolism
malabsorption
Male
methotrexate
Methotrexate - toxicity
Mice
permeation
small intestine
Vitamin A - blood
Vitamin A - pharmacology
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Summary:Oral administration of methotrexate (MTX) to mice causes the damage of small intestine. The permeability of poorly absorbable compound fluorescein isothiocyanate (FITC)-labeled dextran (average molecular weight, 4,400) through the small intestine was studied in vitro using everted segments of the small intestine. The permeability of FITC-dextran increased remarkably in the MTX-treated mice and oral administration of docosahexaenoic acid ethyl ester (DHA) protected the small intestine from the increase in the small intestinal permeability induced by the MTX treatment. The MTX treatment decreased retinol concentration in plasma of mice and the coadministration of DHA maintained its concentration to the level of control mice. The present study showed that DHA protected the small intestine of mice from the MTX-induced damage.
ISSN:0024-3205
1879-0631
DOI:10.1016/S0024-3205(98)00067-8