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.
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Acknowledgements
The authors wish to thank the technical staff of CTBR and Madaus AG for their support. This study was conducted at ClinTrials BioResearch Ltd., Senneville, Quebec, Canada. All procedures were in compliance with the Good Laboratory Practice Regulations of the United States Food and Drug Administration (21 CFR Part 58). The study was also performed in accordance with the Animal Health regulations, on the harmonization of laws, regulations or administrative provisions relating to the protection of animals used for experimental and other scientific purposes and in accordance with the guidelines of the USA National Research Council and the Canadian Council on Animal care (CCAC).
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Mengs, U., Mitchell, J., McPherson, S. et al. A 13-week oral toxicity study of senna in the rat with an 8-week recovery period. Arch Toxicol 78, 269–275 (2004). https://doi.org/10.1007/s00204-003-0534-z
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DOI: https://doi.org/10.1007/s00204-003-0534-z