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References: Laxative

Pharmacology. 1993 Oct;47 Suppl 1:172-7.
Light and electron-microscopic changes in the colon of the guinea pig after treatment with anthranoid and non-anthranoid laxatives.

Mengs U, Rudolph RL.

Madaus AG, Koln, FRG.

Male guinea pigs were treated with senna pods, sennosides, danthron or bisacodyl by gastric intubation for 14 consecutive days. The animals were then killed and the intestine was evaluated by light and electron-microscopic techniques. Macroscopically, the mucosa of the cecum and upper colon was brown in color in the animals receiving anthranoid laxatives. No visible changes were detectable in the bisacodyl group. Evaluation by light and electron microscopy revealed cytoplasmic degeneration and increased apoptosis in the colonic surface epithelium after all laxatives. Most of the resulting apoptotic bodies were found in the lamina propria or had been phagocytosed by stromal macrophages, where they had been transformed into dark brown (anthranoids) or grey to light brown (bisacodyl) pigments. The intestinal changes were most pronounced in the cecum and decreased towards the distal part of the colon. It can be concluded that the morphological changes in the large intestine were similar in anthranoid and non-anthranoid treatment, with the exception that the pigments found in macrophages differed in color and were therefore not always detectable macroscopically.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8234426&dopt=Abstract constipation laxative

Pharmacology. 1993 Oct;47 Suppl 1:187-95.
Effects of 'contact laxatives' on intestinal and colonic epithelial cell proliferation.

Geboes K, Nijs G, Mengs U, Geboes KP, Van Damme A, de Witte P.

Laboratory of Histo- and Cytochemistry, Department of Medical Research, KU Leuven, Belgium.

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.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8234428&dopt=Abstract constipation laxative

Pharmacology. 1993 Oct;47 Suppl 1:209-15.
Two-year carcinogenicity study with sennosides in the rat: emphasis on gastro-intestinal alterations.

Lyden-Sokolowski A, Nilsson A, Sjoberg P.

Medical Products Agency, Division of Pharmacology and Toxicology, Uppsala, Sweden.

A carcinogenicity study was conducted by administering a purified senna extract via the drinking water to Sprague-Dawley rats of each sex for 2 years. The daily doses received were 0, 5, 15 and 25 mg/kg. Histopathological examination was restricted to tissues from the gastro-intestinal tract, liver, kidneys, adrenals and from tissues with any observed abnormalities or masses. A laxative effect was observed in high-dose females, and in mid- and high-dose males. No significant differences in survival were found between treated and control groups. Mean body weight gain was significantly decreased in high-dose males. Increased kidney weights were noted in mid-dose males and females, and high-dose females. Histopathological examination of control and high-dose rats did not indicate any difference in the incidence of neoplastic lesions. As regards non-neoplastic lesions, a treatment- but not dose-related increase in reactive mesenteric lymph node hyperplasia was observed in preterminally sacrificed rats. However, a corresponding increase was not noted in the terminally sacrificed rats or when preterminal and terminal animals were combined. No ultrastructural changes in the myenteric nerve plexus of the colon and jejunum could be detected in the small number of investigated tissue samples. In conclusion, results from the present investigation do not indicate any relationship between long-term administration of purified senna extract and gastrointestinal, liver, kidney or adrenal tumors in the rat.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8234431&dopt=Abstract constipation laxative

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