title: The chronic hepatotoxicity assessment of the herbal formula Zishen Yutai pill.
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-1d-1; i.e. 1 × , 6 × clinical doses) were given orally to rats for 24 weeks. In the chronic liver injury model, 10% CCl4was administered to rats abdominally twice a week at a dose of 5 mL kg-1for 12 consecutive weeks. Administration time started from 4 weeks after the beginning of CCl4treatment. 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-1d-1ZYP in the normal rats and 9.450 g kg-1d-1ZYP in the injury rats.
authors.affiliation: Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100193, China.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Xing
authors.affiliation: Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100193, China.
authors.forename: Xuehong
authors.initials: X
authors.lastname: Deng
authors.affiliation: College of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, Henan, 450001, China.
authors.forename: Jinjin
authors.initials: J
authors.lastname: Shi
authors.affiliation: Changchun University of Chinese Medicine, Changchun, Jilin, 130117, China.
authors.forename: Meishuang
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100193, China.
authors.forename: Guibo
authors.initials: G
authors.lastname: Sun
authors.affiliation: Changchun University of Chinese Medicine, Changchun, Jilin, 130117, China.
authors.forename: Shimin
authors.initials: S
authors.lastname: Tang
authors.affiliation: Guangzhou Baiyunshan Zhongyi Pharmaceutical Co. Ltd, Guangzhou, Guangdong, 510530, China. Electronic address: 13826214009@163.com.
authors.forename: Qiuling
authors.initials: Q
authors.lastname: Huang
authors.affiliation: Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100193, China. Electronic address: sun_xiaobo163@163.com.
authors.forename: Xiaobo
authors.initials: X
authors.lastname: Sun
mesh_terms: D000284:Administration, Oral; D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D015415:Biomarkers / Q000097:blood; D001835:Body Weight / Q000187:drug effects; D002251:Carbon Tetrachloride; D056486:Chemical and Drug Induced Liver Injury / Q000097:blood / Q000209:etiology* / Q000473:pathology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage / Q000633:toxicity*; D004435:Eating / Q000187:drug effects; D005260:Female; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D009336:Necrosis; D009929:Organ Size / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D017207:Rats, Sprague-Dawley; D018570:Risk Assessment; D013997:Time Factors; D036401:Toxicity Tests, Chronic
chemical_list: D015415:Biomarkers; D004365:Drugs, Chinese Herbal; C000615671:Zishen Yutai; D002251:Carbon Tetrachloride; D000410:Alanine Transaminase
keywords: Chronic hepatotoxicity; Herbal formula; No-observed-adverse-effect levels; Polygoni multiflori Radix; Zishen Yutai pill