Cholestyramine feeding lowers number of colonic apoptotic cells in rat

Secondary bile acids that are formed in the colon by bacterial action have the potential property of eliciting pathological conditions. Apoptosis of mucosal epithelial cells is recognized as an adaptation that may counteract such pathologies. Cholestyramine, an anion exchange resin that sequesters bile salts in the gut, could decrease levels of secondary bile salt stress and thus conserve the potency of the protective action. Two groups of rats were studied: those fed 4% cholestyramine and those fed regular rat food. Rats were fed cholestyramine for 7, 14, 21, or 28 d. All animals were evaluated for cell death (apoptosis) using in situ TUNEL staining, and confirmed with single-stranded DNA (ssDNA). The effect of cholestyramine on the proliferating cell nuclear antigen (PCNA) in colonic crypt cells was also examined. Our data shows that animals fed cholestyramine for 28 d show evidence of a significant decrease in the levels of apoptotic cells in their large intestines, particularly goblet cells, when compared with the control animals and no change in cell proliferation. Thus, cholestyramine may serve as an alternative in attenuating apoptosis associated with inflammatory disorders that can result in significant enterocyte and goblet-cell death.