Cytotoxicity of ricinoleic acid (castor oil) and other intestinal secretagogues on isolated intestinal epithelial cells.
Epithelial cells were isolated from hamster small intestine by a technique of vibration and used to measure cytotoxicity in vitro of certain substances known to stimulate intestinal fluid secretion. These secretagogues have laxative properties and produce mucosal damage in vivo. Compounds tested were ricinoleic acid (caster oil), dioctyl sodium sulfosuccinate, oleic acid, sodium deoxycholate and sodium cholate. Cytotoxicity was assessed by: 1) exclusion of trypan blue; 2) release of intracellular (prelabeled) 51Cr; and 3) inhibition of cellular uptake of 3-O-methylglucose. Ricinoleate produced a dose-dependent (0.1-2.0 mM) cytotoxicity as assessed by all three methods. Oleic acid, a nonhydroxylated analog of ricinoleate, was less potent. The dihydroxy bile acid, deoxycholate, was equipotent with ricinoleate, was less potent. The dihydroxy bile acid, deoxycholate, was equipotent with ricinoleate but its trihydroxy congener, cholate, was less potent. Dioctyl sodium sulfosuccinate had cytotoxicity similar in magnitude to that of ricinoleate and deoxycholate. Cytotoxicity of these agents to isolated cells may relate to their secretory potential in vivo, their abilities to produce structural change at the mucosal surface and their laxative properties.
D000818:Animals; D001647:Bile Acids and Salts / Q000494:pharmacology; D003994:Bucladesine / Q000494:pharmacology; D002400:Cathartics / Q000494:pharmacology; D002860:Chromium Radioisotopes; D006224:Cricetinae; D000242:Cyclic AMP / Q000031:analogs & derivatives / Q000494:pharmacology; D004847:Epithelial Cells; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism; D005231:Fatty Acids, Unsaturated / Q000009:adverse effects*; D066298:In Vitro Techniques; D007421:Intestine, Small / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D008647:Mesocricetus; D008757:Methylglucosides / Q000378:metabolism; D009829:Oleic Acids / Q000494:pharmacology; D012277:Ricinoleic Acids / Q000009:adverse effects*; D013386:Succinates / Q000494:pharmacology; D013936:Thymidine; D014343:Trypan Blue
D001647:Bile Acids and Salts; D002400:Cathartics; D002860:Chromium Radioisotopes; D005231:Fatty Acids, Unsaturated; D008757:Methylglucosides; D009829:Oleic Acids; D012277:Ricinoleic Acids; D013386:Succinates; D003994:Bucladesine; D000242:Cyclic AMP; D014343:Trypan Blue; D007545:Isoproterenol; D013936:Thymidine