The chronic hepatotoxicity assessment of the herbal formula Zishen Yutai pill

• Published in: Regulatory toxicology and pharmacology Vol. 83; pp. 81 - 88
• Main Authors: Xing, Xiaoyan, Deng, Xuehong, Shi, Jinjin, Zhang, Meishuang, Sun, Guibo, Tang, Shimin, Huang, Qiuling, Sun, Xiaobo
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Inc 01-02-2017
• Subjects: Administration, Oral; Alanine Transaminase - blood; Animals; Biomarkers - blood; Body Weight - drug effects; Carbon Tetrachloride; Chemical and Drug Induced Liver Injury - blood; Chemical and Drug Induced Liver Injury - etiology; Chemical and Drug Induced Liver Injury - pathology; Chronic hepatotoxicity; Disease Models, Animal; Dose-Response Relationship, Drug; Drugs, Chinese Herbal - administration & dosage; Drugs, Chinese Herbal - toxicity; Eating - drug effects; Female; Herbal formula; Liver - drug effects; Liver - metabolism; Liver - pathology; Necrosis; No-observed-adverse-effect levels; Organ Size - drug effects; Oxidative Stress - drug effects; Polygoni multiflori Radix; Rats, Sprague-Dawley; Risk Assessment; Time Factors; Toxicity Tests, Chronic; Zishen Yutai pill; Polygoni multiflori Radix; No-observed-adverse-effect levels; Zishen Yutai pill; Chronic hepatotoxicity; Herbal formula
• ISSN: 0273-2300; 1096-0295
• DOI: 10.1016/j.yrtph.2016.12.001

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.
•The liver toxicity of ZYP was assessed in both normal and the CCl4 induced chronic liver injury rats.•No any mortality or abnormality in liver toxicity evaluation were noted in ZYP groups.•No solid evidence of liver toxicity under ZYP exposure (9.450 g kg−1 d−1) was found.