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Article Title

Establishment of a standardized animal model of chronic hepatotoxicity using acetaminophen-induced hepatotoxicity in the evaluation of hepatoprotective effects of health food

Abstract

Hepatoprotection is an important issue in Taiwan. Currently, a toxic chemical substance, carbon tetrachloride (CCl4), is used to induce liver damage in animal models that is employed to evaluate the hepatoprotective effects of health food in Taiwan. To provide a more flexible and accessible research model, this study was aimed to establish a standardized animal model of chronic hepatotoxicity using the common drug, acetaminophen; an overdose of this drug causes acute liver damage in experimental animals. Four animal strains from 2 species (ICR mice and BALB/c mice via intraperitoneal injection; Sprague-Dawley rats and Wistar rats via oral administration) were used as subjects in this study. Acetaminophen at various dosages was administered for 8 weeks, and then biochemical and histopathological examinations were performed. The results showed that acetaminophen significantly induced liver damage in mice by intraperitoneal injection, but not in rats by oral administration. The individual variation in BALB/c mice was less than that in ICR mice. Acetaminophen increased serum aspartate transaminase (AST), alanine transaminase (ALT), and glutathione (GSH) content. The glutathione reductase (GRd), superoxide dismutase (SOD), and catalase (CAT) activity were inhibited after acetaminophen injection in BALB/c mice in a dose-dependent manner. The highest dose of acetaminophen was lethal to mice. In terms of histopathological examination, acetaminophen caused hepatic necrosis and inflammation, consistent with the pathological progress found in humans. On the other hand, the liver protective effect of N-acetylcysteine (NAC) in BALB/c mice was analyzed. The data revealed that pretreatment with NAC significantly protected liver from damage induced by 400 mg acetaminophen/kg bw in BALB/c mice, and there was no significant difference between the 600 and 1200 mg NAC/kg bw groups. In conclusion, acetaminophen at the dose of 400 mg/kg bw could induce reproducible liver damage in BALB/c mice, and NAC (600 mg/kg bw) is a suitable protective drug in this animal model for the evaluation of hepatoprotective effects of health food.

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