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Inhibitory action of gemfibrozil on cholesterol absorption in rat intestine
1Department of Pediatrics, Showa General Hospital, Japan.
Abstract:
This study was designed to determine whether gemfibrozil inhibits intestinal lipid absorption. Male Sprague-Dawley rats received an oral dose of 30 mg gemfibrozil/kg body weight for 14 days. Mesenteric lymph cannulation was performed, and a lipid infusion containing 40 micromol/h (35.4 mg/h) of radiolabeled triolein and 2.74 micromol/h (1.06 mg/h) of radiolabeled cholesterol with the addition of 1 mg/h of gemfibrozil was infused intraduodenally at a rate of 3 ml/h for 8 h. The lymph was collected, and the radioactivity levels of the lumen and gut mucosa were measured after the infusion. Lymph cholesterol transport was depressed in gemfibrozil-treated rats, in terms of mass measurements as well as radioactivity in a lesser degree. More radioactive cholesterol remained in the proximal portion of the intestinal lumen and mucosa in the treated rats than in the control rats. More radioactive triglycerides also remained in the proximal intestinal lumen of treated rats, although no difference in lymphatic triglyceride transport was observed between the groups. A significant portion of the radioactive cholesterol remained in the lumen in the gemfibrozil-treated rats. Gemfibrozil increased biliary cholesterol excretion. Thus, this study shows that gemfibrozil inhibits cholesterol absorption in rat intestine.
Insights
Gemfibrozil was found to inhibit intestinal cholesterol absorption in rats. This lipid-lowering drug reduced the transport of cholesterol from the intestine into the lymph.
Area of Science:
- Pharmacology
- Gastroenterology
- Lipid Metabolism
Background:
- Gemfibrozil is a lipid-lowering drug used to treat hyperlipidemia.
- Understanding its effects on intestinal lipid absorption is crucial for its therapeutic application.
Purpose of the Study:
- To investigate the effect of gemfibrozil on intestinal lipid absorption in rats.
- To determine if gemfibrozil inhibits the absorption of cholesterol and triglycerides.
Main Methods:
- Male Sprague-Dawley rats were administered gemfibrozil orally for 14 days.
- Radiolabeled triolein and cholesterol were infused intraduodenally, along with gemfibrozil.
- Lymphatic and intestinal levels of radioactivity were measured to assess lipid absorption.
Main Results:
- Gemfibrozil significantly reduced lymphatic cholesterol transport.
- More radioactive cholesterol remained in the intestinal lumen and mucosa of gemfibrozil-treated rats.
- While triglyceride transport was not significantly affected, more triglycerides remained in the intestinal lumen.
Conclusions:
- Gemfibrozil inhibits cholesterol absorption in the rat intestine.
- The drug increases biliary cholesterol excretion.
- These findings suggest a direct impact of gemfibrozil on intestinal lipid handling.