enprostil and Body-Weight

Effects of multiple oral administration of enprostil ((+/-)-11 alpha,15 alpha-dihydroxy-9-oxo-16-phenoxy-17,18,19,20-tetranorprosta- 4,5,13(t)-trienoic acid methyl ester, TA 84135) (20 micrograms/kg/d) and its solvent propylene carbonate (PC, 100 microliters/kg/d) on body weight gain, liver weight, hepatic drug metabolizing enzyme system and hexobarbital sleeping time were investigated in male rats during a 14-day period. Cytochrome P-450 content (as compared to the untreated control) and cytochrome b5 content (as compared to PC treated group) were slightly, but significantly, reduced in the group given a single oral dose of enprostil. However, these slight reductions were not augmented significantly by repeated administrations of enprostil. Slight but significant increase in microsomal protein content was observed in the group given 14 oral doses of enprostil and PC. Enprostil did not affect the other indicators used to evaluate the status of the hepatic drug metabolizing enzyme system. Additionally, single or multiple oral doses of enprostil or PC showed no effect on the hexobarbital-induced sleeping time. It therefore may be safely concluded that multiple oral administration, both of enprostil and of PC, has very little effect on drug metabolizing enzyme inducing or inhibiting activity in rats.

Topics: Animals; Anti-Ulcer Agents; Body Weight; Enprostil; Hexobarbital; Liver; Male; Microsomes, Liver; Mixed Function Oxygenases; Organ Size; Prostaglandins E, Synthetic; Rats; Rats, Inbred Strains; Sleep; Time Factors

Previous studies have demonstrated that abdominal irradiation alters intestinal uptake of nutrients. The purpose of this study was to determine the effect of an orally administered synthetic prostaglandin E2, enprostil, given on three occasions shortly prior to a single exposure to 600 cGy external abdominal irradiation, on intestinal active and passive transport processes and villus morphology measured 7 days later. Animals were sham-irradiated (CONT) or were exposed to a single dose of 600 cGy external abdominal irradiation (RAD); two and one mornings before the day of irradiation or sham irradiation, and 1 h before irradiation or sham irradiation enprostil was administered. One half of CONT and RAD groups were dosed orally with enprostil, 5 micrograms/kg body weight, and the other half of the CONT and RAD groups were dosed with placebo. Seven days later the in vitro uptake of glucose, galactose, long-chain fatty acids, and cholesterol was determined in the four groups (CONT with and without enprostil, and RAD with and without enprostil). In CONT, enprostil was associated with increased jejunal uptake of glucose and ileal uptake of galactose. In RAD given enprostil, there was increased jejunal uptake of galactose but reduced ileal uptake of glucose and galactose. The expected radiation-associated decline in jejunal galactose uptake was prevented with enprostil. In CONT given enprostil, there was increased jejunal uptake of fatty acid (FA) 14:0 and 16:0 but reduced uptake of FA 18:0, 18:1, and 18:2; enprostil had no effect on lipid uptake in the ileum in CONT.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Body Weight; Cholesterol; Eating; Enprostil; Fatty Acids; Female; Galactose; Gastrointestinal Transit; Glucose; Intestinal Mucosa; Intestines; Lipid Metabolism; Prostaglandins E, Synthetic; Rats; Rats, Inbred Strains

Previous studies have demonstrated that external abdominal irradiation alters intestinal nutrient transport and brush border membrane (BBM) phospholipid content. This study was undertaken to assess the possible protective effect of oral dosing of enprostil, a synthetic E2 prostaglandin, on the BBM marker enzyme and lipid composition of non-irradiated control (CONT) animals and of rats exposed seven days perviously to a single dose of 600 cGy external abdominal irradiation (RAD). Half the CONT and RAD animals were orally dosed with enprostil 5 mcg/kg body weight, two and one mornings before the day of irradiation, and one hour before 600 cGy; the remaining half were dosed with placebo according to the same schedule. BBM were isolated and purified from the animals seven days post-irradiation for analysis of marker enzymes and lipid composition. Radiation was associated with a decline in jejunal and ileal BBM activity of sucrase. Enprostil was associated with a decline in the ratio of alkaline phosphatase/sucrase in jejunal BBM from irradiated rats, despite its preventing a radiation-associated decline in BBM sucrase activity. Radiation was associated with changes in ileal BBM phospholipids, and these alterations were not prevented with enprostil. Furthermore, enprostil given to non-radiated control rats altered BBM composition, such as increased jejunal and ileal lysophosphatidylethanolamine, and lowered ileal BBM sphingomyelin and phosphatidylethanolamine. Thus, enprostil failed to protect the intestine from the effects of abdominal irradiation on BBM phospholipids, but did partially prevent the effect of abdominal irradiation on jejunal sucrase activity.

Topics: Abdomen; Animals; Body Weight; Eating; Enprostil; Enzymes; Female; Ileum; Jejunum; Membrane Lipids; Microvilli; Phosphatidylcholines; Phospholipids; Prostaglandins E, Synthetic; Rats; Rats, Inbred Strains