Reversibility of elemental liquid diet-enhanced methotrexate toxicity by refeeding with chow Journal Article
| Authors: | Harvey, L. P.; McAnena, O. J.; Mehta, B. M.; Daly, J. M. |
| Article Title: | Reversibility of elemental liquid diet-enhanced methotrexate toxicity by refeeding with chow |
| Abstract: | The toxic effects of methotrexate administration [20 mg/kg, bolus intraperitoneally (ip)] to rats fed a regular chow diet (n = 10) was compared with results in animals fed an elemental, chemically defined, liquid diet (n = 10) for 7 days. All animals receiving an elemental diet became anorectic and lethargic within 60 hr of methotrexate injection. All animals in this group subsequently developed enteritis and died within 150 hr. There was no clinical evidence of enteritis in rats fed a regular chow diet and mortality as zero in this group (p < 0.001). In a second study one group of rats (n = 9) was fed a regular chow diet for 7 days; four groups were fed an elemental, chemically defined, liquid diet (n = 9 per group) for 7 days. At 24 hr and 8 hr prior to, or 24 hr after methotrexate administration, one group was refed a regular chow diet; the fourth group was maintained on an elemental liquid diet throughout the study period. All rats fed a regular chow diet survived following methotrexate injection (20 mg/kg, ip). All rats fed an elemental diet throughout the study period died. Those rats refed a regular diet 24 or 8 hr prior to methotrexate injection demonstrated a significant improvement in survival (100% in the 24-hr group, 55% in the 8-hr group). However, those animals refed a regular diet 24 hr after methotrexate injection demonstrated a 100% mortality. A similar study evaluated changes in plasma and bowel methotrexate levels in rats refed either 24 hr or 8 hr prior to 25 hr after methotrexate administration. Serum and bowel tissue methotrexate levels were significantly elevated in rats refed 24 hr after methotrexate injection compared with the other groups. The administration of an elemental, chemically defined liquid diet to rats results in a marked increase in mortality from severe enteritis following methotrexate administration compared with regular chow diet fed animals. These animals demonstrated delayed clearance of methotrexate from serum and from small intestine tissue. This enhanced toxicity is readily reversible by refeeding a regular diet to these animals within 24 hr prior to methotrexate injection. Elemental, chemically defined liquid diets do not afford protection to the gastrointestinal mucosa from the toxic effects of methotrexate. |
| Keywords: | mortality; nonhuman; methotrexate; animal experiment; animalia; gastrointestinal toxicity; diet; drug mechanism; rat; drug clearance; enteritis; drug toxicity; food drug interaction; drug dose; epidemiology; small intestine; pharmacokinetics; intoxication; digestive system; intraperitoneal drug administration; priority journal; preliminary communication |
| Journal Title: | Journal of Parenteral and Enteral Nutrition |
| Volume: | 11 |
| Issue: | 2 |
| ISSN: | 0148-6071 |
| Publisher: | Sage Publications |
| Date Published: | 1987-03-01 |
| Start Page: | 119 |
| End Page: | 123 |
| Language: | English |
| DOI: | 10.1177/0148607187011002119 |
| PUBMED: | 3586300 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Article -- Export Date: 5 February 2021 -- Source: Scopus |
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