Evaluation of APAP-induced hepatotoxicity in BALB/c mice and selection of the suitable drug as positive control
Date Issued
2010
Date
2010
Author(s)
Chen, Ting-Ju
Abstract
According to the report of Department of Health of Taiwan in 2009, chronic liver disease and cirrhosis are the eighth and the tenth leading causs of death, respectively, and liver cancer is the second leading cancer-caused deaths. Therefore, how to mentain liver health is a very important topic in Taiwan. Nowadays, the model of carbon tetrachloride (CCl4)-induced hepatotoxicity is used to evaluate the hepatoprotective effect of on health food. However, CCl4 is recognized as a damge materia and controlled seriously by the government in Taiwan. Acetaminophen (APAP) is a clinically analgesic and antipyretic drug. Previous researches demoustrated that APAP causes liver injury in experimental animals and human being. The aim of this study was to establish an appropriate model of APAP-induced liver injury, and to evaluate the liver protective effects of N-acetylcysteine (NAC) and Silymarin in BALB/c mice. In the acute experiment, the results showed that APAP increased the serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) (>15000 IU/L) in female mice much more than those (500-1000 IU/L) in male mice after APAP intraperitoneal injection. The death rate in female mice (83%) is higher than that (17%) in male ones. It suggested that female mice were not suitable to be used for the experiments. Additionally, male BALB/c mice with APAP- induced liver injury took NAC and Silymarin once daily for 7 days. The results showed that NAC at 600 and 1200 mg/kg bw decreased ALT and AST values in BALB/c mice with APAP-induced hepatotoxicity. The hepatoprotective effect of NAC was also confirmed using histopathological examination of the liver. The date showed that hepatoprotective effect of NAC was better than that of Silymarin. Furthermore, male BALB/c mice were given with NAC once daily on APAP- induced the chronic experiment. It suggested that NAC at 600 and 1200 mg/kg bw effectively improved the APAP-induced liver injury in BALB/c mice. Therefore, these results showed that NAC (600 mg/kg bw) is better to be positive control in both acute and chronic APAP-induced liver injury in BALB/c mice for evaluation of the heptoprotective effect of health food.
Subjects
acetaminophen
N-acetylcysteine
Silymarin
liver protective effect
health food
SDGs
Type
thesis
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