Two-Year Carcinogenicity Study with Sennosides in the Rat: Emphasis on Gastro-lntestinal Alterations

Abstract

A carcinogenicity study was conducted by administering a purified senna extract via the drinking water to Sprague-Daw-ley 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 gastrointestinal 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.

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

“…There is no evi dence that in the rodent model tumors would develop based on these changes. In the case of sennosides, this is also supported by the find ings of Lyden-Sokolowski et al [20] who found no cancerogenic potential of a senna extract given to rats over a period of 2 years.…”

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).…”

“…These findings led to an increase in concern about the safety of anthranoid laxatives since it has been speculated that the chronic use might cause colorectal cancer in humans (Westendorf et al 1990;Siegers 1992;Westendorf 1993). It is important to note that senna has never been shown to increase the incidence of colorectal cancer in nonclinical or clinical studies (Kune 1993;Lyden-Sokolowski et al 1993;Nusko et al 1993;Loew et al 1997).…”

Analytics of Senna Drugs with Regard to the Toxicologicai Discussion of Anthranoids

“…Drugs and preparations which vary in a wide range in respect to their HA content become comparable with the risk index. The knowl edge of the potential aloe-emodin and emodin contents in senna preparations administered for genotoxicity [5], cancerogenicity [11], and pharmacokinetic studies [ 12] is of high impor tance for the interpretation of their results.…”