Effects of ‘Contact Laxatives’ on Intestinal and Colonic Epithelial Cell Proliferation

Abstract

Experimental studies indicate that laxatives may induce epithelial damage. In addition, some laxatives induce the release of prostaglandins. Epithelial cell damage and release of prostaglandins are two pathways by which epithelial cell proliferation could be influenced. Furthermore, fermentable laxatives like lactulose may influence large intestine cell proliferation by the trophic effect of the fermentation products such as short-chain fatty acids. For these reasons an in vivo study in rats was performed to compare the short- and long-term effect of sennosides, bisacodyl, sodium picosulfate and lactulose on epithelial cell proliferation in the ileum and large intestine. Cell proliferation was examined by the BrdUrd labelling technique after 2, 6 and 12 weeks of continuous treatment. Studies in control animals show that the Labeling Index (LI) is higher in the cecum compared with other segments of the colon, and higher in the ileum than in the colon. Treatment with sennosides, bisacodyl and sodium picosulfate does not influence the LI in the ileum and induces no statistically significant increase of the LI when the treated groups are compared with the control group. The proliferative pattern along the crypts remains unchanged with all the laxatives throughout the study. It appears therefore that ‘contact’ laxatives have no major influence on ileal and colonic epithelial cell proliferation and should not be regarded as tumor-promoting substances.

Effects of Sennosides and Nonanthranoid Laxatives on Cytochemistry of Epithelial Cells in Rat Colon

“…This study is a continuation of the one reported by Geboes et al [4], where cell prolif eration was measured.…”

“…These findings appear to be particularly important because of minimal changes found in measurements of cell proliferation under the same conditions [4], In one of the mea surements (AE1 cytokeratin) the changes ap pear to be structural, and measurements of mucin could be derived from secretory changes with or without structural alterations. This enlarged series of biomarkers would ap pear to make available more comprehensive evaluations of cellular structure and function involving colonic epithelial cell proliferation and differentiation.…”

“…Tis sues from the rectum, middle colon and cecum were taken for these analyses together with those analyzed for cell proliferation by Geboes ct al. [4]; they were fixed in 10% buffered formalin, and also in 95% of eth anol. Four-micrometer tissue sections were prepared after routine processing for hematoxylin and eosin, acidic mucins (high iron diamine-Alcian blue) and immunohistochemical studies for lectin soybean agglu tinin (SBA) and cytokeratin AE1.…”

Effects of inflammation on cell proliferation in the myenteric plexus of the guinea-pig ileum

“…The guinea pig was chosen, as the myenteric plexus of this species is well characterized, and a reliable model of inflammation has been established. The incorporation of the thymidine analogue bromodeoxyuridine (5-bromo-2-deoxyuridine; BrdU) into replicating DNA was used to label proliferative cells (Gratzner 1982;Potten et al 1992;Geboes et al 1993), and single-and double-labelling immunohistochemistry was used to assess the occurrence of BrdU in specific cells of the myenteric plexus.…”

A 13-week oral toxicity study of senna in the rat with an 8-week recovery period

“…Increased cell proliferation in the rat intestine has also been reported for sennoside A and other active laxative compounds like danthron, bisacodyl and magnesium sulfate (Toyoda et al 1994). However, increased cell proliferation of the large intestine was not observed in other studies on rats following long-term exposure to a senna extract or pure sennosides (Mengs 1988;Geboes et al 1993;Lyden-Sokolowski et al 1993).…”