Lipid accumulation in jejunal and colonic mucosa following chronic cholestyramine (Questran) feeding.
The hypolipidemic agent, cholestyramine (Questran), when fed to rats inhibits intestinal absorption of cholesterol and triglycerides and causes significant epithelial cell damage in both small and large intestine. In this study, we report significant accumulation of lipids in the mucosal layer of both jejunum and colon in rats administered 2% cholestyramine for a four-week period, when compared to a control group maintained on regular chow. The total lipid increment with cholestyramine was 4.7-fold in the jejunum and 3.7-fold in the colon. The triglyceride fraction increased substantially in the small but not the large intestine. Relative phospholipid levels decreased in the treated jejunum but not in the colon. The biochemical data were reflected in morphological evidence of lipid-laden enterocytes obtained by light and transmission electron microscopy. Since cholestyramine has been shown to sequester 99.8% of micellar phospholipid in vitro, it is concluded that the presence of cholestyramine in the intestinal lumen may interfere with phospholipid availability for chylomicron synthesis and serosal lipid exit from the epithelium. This unusual deposition of lipid within the mucosal layer may also be correlated with the known cocarcinogenic effect of this resin in experimentally induced intestinal cancer.
D000818:Animals; D002792:Cholestyramine Resin / Q000008:administration & dosage* / Q000494:pharmacology; D003106:Colon / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D004075:Diglycerides / Q000378:metabolism; D004848:Epithelium / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D007408:Intestinal Absorption / Q000187:drug effects; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism; D007583:Jejunum / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D050356:Lipid Metabolism; D008297:Male; D008871:Microvilli / Q000648:ultrastructure; D010743:Phospholipids / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D014280:Triglycerides / Q000378:metabolism
D004075:Diglycerides; D005230:Fatty Acids, Nonesterified; D010743:Phospholipids; D014280:Triglycerides; D002792:Cholestyramine Resin