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Journal of Endotoxin Research, Vol. 13, No. 3, 176-188 (2007)
DOI: 10.1177/0968051907081102

Down-regulation of TGFß1 and leptin ameliorates thioacetamide-induced liver injury in lipopolysaccharide-primed rats

Huan-Nan Chen

Institute of Biotechnology, National Dong Hwa University, Hualien, Taiwan

Sabrina Fan

Institute of Biotechnology, National Dong Hwa University, Hualien, Taiwan

Ching-Feng Weng

Institute of Biotechnology, National Dong Hwa University, Hualien, Taiwan, cfweng{at}mail.ndhu.edu.tw

Pretreatment with a low dose of bacterial endotoxin (lipopolysaccharide, LPS) caused the reduction of cytochrome P450 (CYP) enzymes and inflammatory factors which are capable of protecting the liver from a lethal LPS challenge. However, the effects of LPS pretreatment on the expression of transforming growth factor ß1 (TGFß1) and leptin in thioacetamide (TAA)-induced liver fibrosis remain unknown. In this study, Sprague-Dawley rats were pretreated intraperitoneally with LPS (5 mg/kg body weight) for 24 h, and subsequently treated with TAA (200 mg/kg body weight/ 3 days) for 1 month to examine the effects of LPS on TAA-injured rats. LPS pretreatment was associated with lower granulation and lower (P < 0.05) GOT/GPT than in TAA-injured rats. The LPS-pretreated group had less collagen (Sirius red histochemical staining). Semiquantitative RT-PCR showed that the levels of collagen 3 and TGFß1 mRNAs were lower (P < 0.05) in the liver of LPS-pretreated rats than in TAA-injured rats. TGFßRI mRNA in the liver of LPS-pretreated rats exceeded (P < 0.05) that in TAA-injured rats. LPS pretreatment reduced the leptin content (Western blot) below that of TAA-injured rats. These results imply that LPS pretreatment (endotoxin tolerance) alleviates the TAA-induced liver fibrosis of rats by reducing TGFß1 and leptin content.

Key Words: Thioacetamide • lipopolysaccharide • endotoxin tolerance • TGFß1 • leptin • liver injury.


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