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The chronic hepatotoxicity assessment of the herbal formula Zishen Yutai pill
Institution:1. Institute for Advancing Translational Medicine in Bone & Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China;2. Hong Kong Baptist University Branch of State Key Laboratory of Chemo/Biosensing and Chemometrics of Hunan University, Hong Kong, China;3. Institute of Integrated Bioinfomedicine & Translational Science, HKBU Shenzhen Research Institute and Continuing Education, Shenzhen, China;4. Academician CHAN Sun Chi Albert Workroom for Advancing Translational Medicine in Bone & Joint Diseases, Kunshan RNAi Institute, Kunshan Industrial Technology Research Institute, Kunshan, Jiangsu, China;5. School of Chinese Medicine, Department of Orthopaedics & Traumatology, The Chinese University of Hong Kong, Hong Kong, China;6. Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing 100700, China;7. State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing, China;8. Molecular Science and Biomedicine Laboratory, State Key Laboratory of Chemo/Bio-Sensing and Chemometrics, College of Chemistry and Chemical Engineering, College of Biology, Collaborative Innovation Center for Chemistry and Molecular Medicine, Hunan University, Changsha, China;9. Laboratory of Nucleic Acid Technology, Institute of Molecular Medicine, Peking University, Beijing, China
Abstract:Zishen Yutai pill (ZYP) is an oriental herbal formula, while hepatotoxicity assessment of ZYP was rarely evaluated. Therefore, our aim is to re-evaluate its hepatotoxicity in both normal and carbon tetrachloride (CCl4) induced chronic liver injury rats. In the normal model, two doses of ZYP (1.575 and 9.450 g kg−1 d−1; i.e. 1 × , 6 × clinical doses) were given orally to rats for 24 weeks. In the chronic liver injury model, 10% CCl4 was administered to rats abdominally twice a week at a dose of 5 mL kg−1 for 12 consecutive weeks. Administration time started from 4 weeks after the beginning of CCl4 treatment. Toxicological parameters included mortality, body weight, food consumption, clinical signs, biochemical parameters, gross observation, organ weight, necropsy findings and histopathology were monitored. In the normal model, we found no any mortality or abnormality in clinical signs, relative liver weight, biochemical parameters and histopathology in ZYP treatment groups. In the chronic liver injury model, liver damage related parameter such as ALT was elevated at the high dose of ZYP treatment in contrast to the CCl4-treated group (P < 0.01). In histopathological assessment, there were no significant difference between ZYP treatment groups and CCl4-treated group. No observed adverse effect on livers were established for 9.450 g kg−1 d−1 ZYP in the normal rats and 9.450 g kg−1 d−1 ZYP in the injury rats.
Keywords:Zishen Yutai pill  Herbal formula  Chronic hepatotoxicity  Polygoni multiflori Radix  No-observed-adverse-effect levels
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