Influence of a highly purified senna extract on colonic epithelium.
BACKGROUND
Chronic use of sennoside laxatives often causes pseudomelanosis coli. A recent study suggested that pseudomelanosis coli is associated with an increased colorectal cancer risk. A single high dose of highly purified senna extract increased proliferation rate and reduced crypt length in the sigmoid colon compared to historical controls.


OBJECTIVE
To evaluate in a controlled study the effects of highly purified senna extract on cell proliferation and crypt length in the entire colon and on p53 and bcl-2 expression.


METHODS
Addition of a senna extract to colonic lavage was studied in 184 consecutive outpatients. From 32 randomised patients, 15 with sennosides (Sen), 17 without (NSen), biopsies were taken. Proliferative activity was studied in 4 areas of the colon, using 5-bromo-2'-deoxyuridine labelling and immunohistochemistry (labelling index, LI). Expression of p53 and bcl-2 in the sigmoid colon was determined immunohistochemically.


RESULTS
Crypts were shorter in Sen than in NSen in the transverse and sigmoid colon. LI was higher in Sen than in NSen in the entire colon. No difference in p53 expression was seen. Bcl-2 expression was higher in both groups when crypts were shorter and/or proliferation was increased.


CONCLUSIONS
Sennosides induce acute massive cell loss probably by apoptosis, causing shorter crypts, and increased cell proliferation and inhibition of apoptosis to restore cellularity. These effects may reflect the mechanism for the suggested cancer-promoting effect of chronic sennoside use.
van Gorkom
B A
BA
Department of Gastroenterology and Hepatology, University Hospital, Groningen, The Netherlands.
Karrenbeld
A
A
van Der Sluis
T
T
Koudstaal
J
J
de Vries
E G
EG
Kleibeuker
J H
JH
D000293:Adolescent; D000328:Adult; D000368:Aged; D017209:Apoptosis; D001707:Biopsy, Needle; D002400:Cathartics / Q000008:administration & dosage / Q000009:adverse effects*; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D003106:Colon / Q000187:drug effects* / Q000473:pathology*; D003113:Colonoscopy; D015179:Colorectal Neoplasms / Q000139:chemically induced / Q000473:pathology; D016001:Confidence Intervals; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011336:Probability; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis*; D012016:Reference Values; D018570:Risk Assessment; D012676:Senna Extract / Q000008:administration & dosage / Q000009:adverse effects*; D016159:Tumor Suppressor Protein p53 / Q000032:analysis*
D002400:Cathartics; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D012676:Senna Extract