Experimental study on the "dose-time-toxicity" relationship of hepatotoxicity induced by a single-dose of Chaiqin Qingning capsule(柴芩清宁胶囊)and Ganmaoling capsule（感冒灵胶囊）in mice
10.3760/cma.j.issn.1008-5734.2016.04.003
- VernacularTitle:柴芩清宁胶囊与感冒灵胶囊单次给药对小鼠肝毒性的“量-时-毒”关系对比研究
- Author:
Xiang AN
1
;
Jingfei GAO
1
;
Xuansheng DING
1
Author Information
1. 中国药科大学基础医学与临床药学学院临床药学系精准医学研究室, 南京,211198
- Publication Type:Journal Article
- Keywords:
Drug-induced liver injury;
Dose-response relationship,drug;
Toxicity tests;
Mice;
Chaiqin Qingning capsule;
Ganmaoling capsule.
- From:
Adverse Drug Reactions Journal
2016;18(4):249-254
- CountryChina
- Language:Chinese
-
Abstract:
Objective To compare the " dose-time-toxicity" relationship of acute liver injury in mice induced by a single-dose of Chaiqin Qingning capsule or Ganmaoling capsule.Methods " Time-toxicity" study:the mice were divided into 19 subgroups (10 mice in each subgroup),including 9 Chaiqin Qingning capsule subgroups,9 Ganmaoling capsule subgroups,and 1 normal control group (treated with distilled water).The mice in the Chaiqin Qingning capsule group were treated with a single intragastric administration with 1.65 times of clinically equivalent dose (ED) (equal to 95.42 times of 70 kg normal adult daily dose) of the drug suspension.The mice in the Ganmaoling capsule group were treated with a single intragastric administration with 1.554 times of ED (equal to 52.53 times of 70 kg normal adult daily dose) of the drug suspension.The mice in the Chaiqin Qingning capsule group and Ganmaoling capsule group were divided into 1 h,2 h,4 h,8 h,12 h,24 h,48 h,72 h and 96 h subgroups after administration,respectively." Dose-toxicity" study:the mice were divided into 13 subgroups (10 mice in each subgroup),including 6 Chaiqin Qingning capsule subgroups (according to dose,the mice were divided into ED,1.6ED,1.62ED,1.63ED,1.64ED and 1.65ED subgroups;351.00,561.60,898.56,1 437.70,2 300.31 and 3 680.50 mg/kg,respectively),6 Chaiqin Qingning capsule subgroups (according to dose,the mice were divided into ED,1.55ED,1.552ED,1.553ED,1.554ED and 1.555ED subgroups;390.00,604.50,936.98,1 452.31,2 251.08 and 3 489.18 mg/kg,respectively),and 1 normal control group (treated with distilled water)."Time-toxicity" was studied at different times after the drugs administration and " dose toxicity" was studied at 12 h after administration.General state and body weight of mice were observed.The changes of the levels of ALT,AST,and ALP in serum and organ index of liver,spleen,and thymus were tested.Results The difference of serum levels of ALT,AST,and ALP and liver,spleen,and thymus organ index of mice between the 9 different time subgroups and the 6 different dose subgroups in Chaiqin Qingning capsule group and the normal control group were not statistically significant (all P ＞ 0.05).The ALT,AST,and ALP levels in the 2 h,4 h,8 h,12 h,and 24 h subgroups and the 1.553ED,1.554ED,and 1.555ED subgroups,the serum levels of ALT in the 48 h subgroup,the serum levels of ALT and AST in the 1.552ED subgroup,and liver organ index in mice in the 8 h and 12 h subgroups and the 1.553ED,1.554ED,1.555ED subgroups in the Ganmaaoling capsule group were significantly higher than those in the normal control group (P ＜ 0.05,P ＜ 0.01).The serum levels of ALT,AST,ALP,and liver organ index in the 12 h subgroup were the highest in the " time-toxicity" study [(1 017.0 ±342.6) U/L,(281.3 ±60.1) U/L,(171.8 ±43.5) U/L,(6.76 ±0.60) g/100 g],and the serum levels of ALT,AST,ALP,and liver organ index in the 1.555ED subgroup were the highest in the "dose-toxicity" study [(2 930.6 ± 661.5) U/L,(888.8 ± 180.6) U/L,(392.7 ± 42.4) U/L,(7.21 ± 1.12) g/100 g].Conclusions A single large dose of Chaiqin Qingning capsule did not induce significant hepatotoxicity in mice.A single large dose of Ganmaoling capsule could induce acute liver injury in mice and showed a significant "dose-time-toxicity" relationship.
