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

Abstract

Senna was administered by gavage to Sprague Dawley rats once daily at dose levels of 0, 100, 300, 750 or 1500 mg/kg for up to 13 consecutive weeks followed by an 8-week recovery period for selected animals. Dose- and treatment-related clinical signs included abnormal feces, which were seen to varying degrees from animals at 300 mg/kg per day and more. Animals receiving 750 or 1500 mg/kg per day had significantly reduced body weight gain (males only) and, related to the laxative properties of senna, increased water consumption and notable changes in electrolytes in both serum and urine. At both the terminal and recovery phase necropsy, an increase in absolute and relative kidney weights was seen for male and female animals receiving 750 and/or 1500 mg/kg per day. A dark discoloration of the kidneys was observed at necropsy along with histopathological changes in the kidneys (slight to moderate tubular basophilia and pigment deposits) at 300 mg/kg and above. However, there were no indications in laboratory parameters of any renal dysfunction. In addition, for all treated groups, minimal to slight hyperplasia was recorded in the forestomach and large intestine. Following 8 weeks of recovery, with the exception of the brown pigment in the kidneys, there were no histopathological abnormalities. Thus, the biochemical and morphological changes seen following 13 weeks of treatment of senna significantly reversed following 8 weeks of recovery.

Is Senna Laxative Use Associated to Cathartic Colon, Genotoxicity, or Carcinogenicity?

“…Likewise, a slight hyperplasia in the large intestine was observed. After an eight-week suspension of the use of the laxative, no histopathological anomalies were found, with the exception of the brown pigmentation of the kidneys [6]. …”

“…Senna contains various anthranoids, where the most important are sennosides A and B; followed by aloe-emodin, emodin, and chrysophanol [6]. The sennosides, main active metabolite of senna, show a very low toxicity in rats [7] and their genotoxic activity in bacterial strains as well as mammal cells, in the cases where it was significant, was classified as weak [8–11].…”

Influence of Repeated Senna Laxative Use on Skin Barrier Function in Mice

“…1B, C), which indicated that constipation occurred in mice. Repeated senna administration caused functional intestinal disturbance20 and epithelial hyperplasia21. Therefore, it was suggested that structural change of the intestine was also caused in mice receiving senna.…”

Effects of the toluene and methanol extract of Senna (Cassia angustifolia Vahl) on viability and proliferation HeLa cells

“…The laxative property of Senna is based on two glycosides sennoside A and sennoside B [11]. The strongest laxative sennosides A and B, shows the lowest toxicity, while fraction that contains rhein 8-glycoside with a minimum efficiency laxative, has increased toxicity [12,13]. Emodin and aloe-emodin showed toxic effects on Salmonella typhimurium, on hepatocytes and fibroblasts from mouse [14].…”

“…The presence of chemical compounds in the extract depended on the solvent that was used. In addition to that, the incubation process lead to the interaction of the compounds in the extract, as well as to the interaction with their metabolic products, which may have had first an inhibitory effect and later a stimulatory effect on cells at certain extract concentrations [12,13].…”