Effects of methotrexate on intestinal transit in rats
A study was designed to determine the effects of methotrexate (MTX) on rat intestinal transit. Adult male rats were implanted with indwelling cannulas in the proximal duodenum 5 to 7 days prior to experimentation. After recovery from surgery, groups of animals were treated with either saline (1.0 ml/kg/day) or MTX at 0.5, 1.25, 3.125, or 7.8 mg/kg/day (ip) for 3 consecutive days (Days 1-3). On each of the next 5 consecutive days (Days 4-8) weight and intestinal transit determinations were made in animals from each test group following a 24-hr fast. Intestinal transit was determined by measuring the progression of an intraduodenally administered bolus of radioactive chromium (Na/sub 2//sup 51/CrO/sub 4/, 0.5 mu Ci) through the small intestine. When compared with saline-treated controls, intestinal transit was significantly (p less than 0.05) increased on 1 or more of the 5 test days in animals treated with doses of MTX greater than 0.5 mg/kg/day. When compared with animals treated with saline, animals treated with MTX lost a greater percentage of their initial body weight after the fast period. Plasma concentrations of MTX, determined at various time intervals after 3.125 mg/kg given daily for 1 to 3 consecutive days, peaked at 15 and 30 min after each injection and diminished to undetectable levels after 4 hr. The results indicate that 3 days of parenteral therapy with MTX significantly increases rat intestinal transit. The intestinal effects appear to be transient and are proportional to the total dose of drug administered over the 3-day period. The intestinal effects of MTX occur from 1 to several days after peak plasma concentrations of drug and are associated with a reduced ability to sustain body weight after a 24-hr fast.
- OSTI ID:
- 5858299
- Journal Information:
- Fundam. Appl. Toxicol.; (United States), Vol. 5
- Country of Publication:
- United States
- Language:
- English
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59 BASIC BIOLOGICAL SCIENCES
METHOTREXATE
BIOLOGICAL EFFECTS
SMALL INTESTINE
BIOLOGICAL FUNCTIONS
CHROMIUM 51
DOSE-RESPONSE RELATIONSHIPS
RATS
TRACER TECHNIQUES
WEIGHT
ANIMALS
ANTIMETABOLITES
BETA DECAY RADIOISOTOPES
BODY
CHROMIUM ISOTOPES
DIGESTIVE SYSTEM
DRUGS
ELECTRON CAPTURE RADIOISOTOPES
EVEN-ODD NUCLEI
FUNCTIONS
GASTROINTESTINAL TRACT
INTERMEDIATE MASS NUCLEI
INTESTINES
ISOTOPE APPLICATIONS
ISOTOPES
MAMMALS
NUCLEI
ORGANS
RADIOISOTOPES
RODENTS
VERTEBRATES
560305* - Chemicals Metabolism & Toxicology- Vertebrates- (-1987)
550501 - Metabolism- Tracer Techniques