Cholestyramine feeding Lowers Number of Colonic Apoptotic Cells In Rat - Journal of Toxicology and Environmental Health

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Journal of Toxicology and Environmental Health, Part A, 68:1963–1975, 2005

Copyright© & Francis Inc.

ISSN: 1528–7394 print / 1087–2620 online

DOI: 10.1080/15287390500227050

CHOLESTYRAMINE FEEDING LOWERS NUMBER OF COLONIC

APOPTOTIC CELLS IN RAT

Leon Lack1, Hagir B. Suliman2, Ali A. Rahman1,

Mohammed B. Abou-Donia1

1Department of Pharmacology, Cancer Biology, Durham, North Carolina,

USA

2Department of Anesthesiology, Duke University Medical Center, Durham,

North Carolina, USA

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.