Recombinant bovine pancreatic trypsin inhibitor protects the liver from carbon tetrachloride-induced acute injury in mice.
OBJECTIVE
Toxicity caused by pharmacological and chemical substances, including carbon tetrachloride (CCl(4)), 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 CCl(4)-induced liver injury in mice.


METHODS
Mice were treated with CCl(4) 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-alpha level, respectively.


RESULTS
CCl(4) 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 CCl(4)-induced disruption of liver function. Importantly, rBPTI reduced CCl(4)-induced liver oxidative stress response and pro-inflammatory cytokine production.


CONCLUSIONS
These results indicated that rBPTI exerted a protective effect on CCl(4)-induced liver injury in mice. Thus, rBPTI may have potential application for prevention of liver injury induced by metabolism of drugs and toxic substances.
Yang
Lili
L
Department of Immunology, Key Laboratory of Cancer Prevention and Therapy, Tianjin Cancer Institute and Hospital, Tianjin Medical University, Tianjin, PR China.
Dong
Wen
W
Yan
Fang
F
Ren
Xiubao
X
Hao
Xishan
X
D000818:Animals; D007611:Aprotinin / Q000096:biosynthesis / Q000302:isolation & purification / Q000627:therapeutic use*; D002251:Carbon Tetrachloride / Q000633:toxicity*; D056486:Chemical and Drug Induced Liver Injury / Q000097:blood / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D004305:Dose-Response Relationship, Drug; D005234:Fatty Liver / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control; D005260:Female; D005978:Glutathione / Q000378:metabolism; D007249:Inflammation / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D051379:Mice; D009336:Necrosis / Q000139:chemically induced / Q000517:prevention & control; D020556:Neutrophil Infiltration / Q000187:drug effects; D009929:Organ Size / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D020011:Protective Agents / Q000302:isolation & purification / Q000378:metabolism / Q000627:therapeutic use*; D011897:Random Allocation; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000302:isolation & purification / Q000627:therapeutic use; D012720:Severity of Illness Index; D013482:Superoxide Dismutase / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
D020011:Protective Agents; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D008315:Malondialdehyde; D007611:Aprotinin; D002251:Carbon Tetrachloride; D013482:Superoxide Dismutase; D005978:Glutathione