An oral carcinogenicity and toxicity study of senna (Tinnevelly senna fruits) in the rat

Abstract

Senna (Tinnevelly senna fruits), a known laxative derived from plants, was administered by gavage to Sprague-Dawley (Crl:CD (SD) BR) rats once daily at dose levels of 0, 25, 100 and 300 mg/kg/day for up to 104 consecutive weeks. Based upon clinical signs related to the laxation effect of senna, the highest dose (300 mg/kg/day) was considered to be a maximum tolerated dose. Sixty animals per sex were assigned to the control and dose groups. Assessments included clinical chemistry, hematology, full histology (control and high-dose groups; in addition, low and mid dose: intestinal tract, adrenals, liver, kidneys, brain and gross lesions) and toxicokinetics. The primary treatment-related clinical observation was mucoid feces seen at 300 mg/kg/day. When compared to controls, animals administered 300 mg/kg/day had slightly reduced body weights, increased water consumption and notable changes in electrolytes in serum (increases in potassium and chloride) and urine (decreases in sodium, potassium and chloride). The changes in electrolytes are most likely physiologic adaptations to the laxative effect of senna. At necropsy, dark discoloration of the kidneys was observed in animals in all treated groups. Histological changes were seen in the kidneys of animals from all treated groups and included slight to moderate tubular basophilia and tubular pigment deposits. In addition, for all treated groups, minimal to slight hyperplasia was evident in the colon and cecum. These histological changes, together with the changes seen in the evaluation of clinical chemistry and urine parameters, have been shown to be reversible in a previous 13-week rat study of senna. No treatment-related neoplastic changes were observed in any of the examined organs. Based upon these data, it is concluded that senna is not carcinogenic even after daily administration for 2 years at dosages of up to 300 mg/kg/day in Sprague-Dawley rats.

Cancer-related constipation

“…Chronic use of senna has raised fears of melanosis coli being a premalignant state as well as fears of neuronal damage. Fortunately, long-term studies in rats have shown no evidence of carcinogenicity or enteric nervous damage, but the issues are not definitively settled in humans [19,20]. Carbohydrate osmotic agents work because humans cannot hydrolyze their disaccharide bonds; however, colonic bacteria can hydrolyze this bond, and resultant metabolism produces gas, which can lead to uncomfortable bloating.…”

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

“…To clarify the detailed mechanisms of skin disruption, we will perform another experiment and administer an anti-tryptase antibody or antioxidant to directly block tryptase or oxidative stress in further research. There have been several reports about the toxicity of chronic senna administration on the intestine2627, however, there is no report about the toxicity on skin. Significant body weight loss was observed after senna treatment, however, weight loss was less likely to have an influence on the skin barrier function because similar tendency was also observed in other groups.…”

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].…”