期刊
JOURNAL OF PHARMACY AND PHARMACOLOGY
卷 62, 期 3, 页码 332-338出版社
WILEY
DOI: 10.1211/jpp.62.03.0007
关键词
bovine pancreatic trypsin inhibitor; carbon tetrachloride; liver injury
资金
- National High Technology Research and Development Program of China [2004AA205020]
Objectives Toxicity caused by pharmacological and chemical substances, including carbon tetrachloride (CCl4), is a major pathological factor for liver injury. Therefore, strategies to prevent toxicity are needed for maintaining a healthy liver. This study was designed to determine whether recombinant bovine pancreatic trypsin inhibitor (rBPTI), a non-specific serine protease inhibitor, prevents CCl4-induced liver injury in mice. Methods Mice were treated with CCl4 in the presence or absence of co-treatment with rBPTI. Liver sections were prepared for histopathological assessment. Liver function was evaluated by detecting serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) and liver index. Liver oxidative stress and inflammation were examined by detecting the liver malondialdehyde level and glutathione and superoxide dismutase activity, and serum tumour necrosis factor-a level, respectively. Key findings CCl4 induced hepatocyte necrosis, inflammatory cell infiltration and fatty degeneration, which were ameliorated by co-treatment with rBPTI in a concentration-dependent manner. Furthermore, rBPTI prevented CCl4-induced disruption of liver function. Importantly, rBPTI reduced CCl4-induced liver oxidative stress response and proinflammatory cytokine production. Conclusions These results indicated that rBPTI exerted a protective effect on CCl4-induced liver injury in mice. Thus, rBPTI may have potential application for prevention of liver injury induced by metabolism of drugs and toxic substances.
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