Mingxiao Zhang1, Xiaosong Hu2, Shuai Li3, Chen Lu3, Juan Li3, Yonghua Zong3, Wenqian Qi3, Huijun Yang4. 1. Department of Morphology Lab, Chengdu Medical College, Sichuan Chengdu, China; Luoyang Vocational and Technical College, Luoyang, Henan, China. Electronic address: 595112042@qq.com. 2. Department of Morphology Lab, Chengdu Medical College, Sichuan Chengdu, China. Electronic address: woodwind@sohu.com. 3. Department of Morphology Lab, Chengdu Medical College, Sichuan Chengdu, China. 4. Department of Morphology Lab, Chengdu Medical College, Sichuan Chengdu, China. Electronic address: he500209@163.com.
Abstract
BACKGROUND AND AIM: Liver fibrosis is a worldwide clinical issue. It has been well established that liver fibrosis is characterized of excessive extracellular matrix (ECM) deposition in chronically damaged livers. Accumulating evidences have suggested that ethyl pyruvate (EP) is a potential useful agent for preventing from hepatic injury. The aim of this study was to evaluate the protective effects of the EP against liver fibrosis induced by carbon tetrachloride (CCl4) in rats. METHOD: Rats were randomly divided into control group, CCl4 group and CCl4+EP group, which with and without EP administration. Liver fibrosis was evaluated by serum biochemical parameters levels, Masson's trichromic staining and immunohistochemistry. Q-RTPCR was used to indicate genes expression. ELISA was used to detect proteins level. RESULTS: This study demonstrates that Toll-like receptors 4 (TLR4)/nuclear factor kappa B (NF-κB) signal is an important regulator of liver fibrosis while TLR4/NF-κB mRNA and protein levels reduced during HSCs activation. In addition, down-regulated high-mobility group box 1 (HMGB1) expression reduced NF-κB transcription and phosphorylation, which inhibited HSCs activation by blocking the TLR4 signal. Moreover, EP contributed to an increase in the ratio of matrix metalloproteinase (MMPs) to tissue inhibitor of matrix metalloproteinase (TIMPs), which might facilitate the degradation of the ECM. In CCl4-induced liver fibrosis rats, additional EP injection resulted in decreased ECM deposition and improved liver function. CONCLUSION: In conclusion, the present findings indicated that EP might be an effective agent for anti-fibrotic therapy.
BACKGROUND AND AIM: Liver fibrosis is a worldwide clinical issue. It has been well established that liver fibrosis is characterized of excessive extracellular matrix (ECM) deposition in chronically damaged livers. Accumulating evidences have suggested that ethyl pyruvate (EP) is a potential useful agent for preventing from hepatic injury. The aim of this study was to evaluate the protective effects of the EP against liver fibrosis induced by carbon tetrachloride (CCl4) in rats. METHOD:Rats were randomly divided into control group, CCl4 group and CCl4+EP group, which with and without EP administration. Liver fibrosis was evaluated by serum biochemical parameters levels, Masson's trichromic staining and immunohistochemistry. Q-RTPCR was used to indicate genes expression. ELISA was used to detect proteins level. RESULTS: This study demonstrates that Toll-like receptors 4 (TLR4)/nuclear factor kappa B (NF-κB) signal is an important regulator of liver fibrosis while TLR4/NF-κB mRNA and protein levels reduced during HSCs activation. In addition, down-regulated high-mobility group box 1 (HMGB1) expression reduced NF-κB transcription and phosphorylation, which inhibited HSCs activation by blocking the TLR4 signal. Moreover, EP contributed to an increase in the ratio of matrix metalloproteinase (MMPs) to tissue inhibitor of matrix metalloproteinase (TIMPs), which might facilitate the degradation of the ECM. In CCl4-induced liver fibrosisrats, additional EP injection resulted in decreased ECM deposition and improved liver function. CONCLUSION: In conclusion, the present findings indicated that EP might be an effective agent for anti-fibrotic therapy.
Authors: Nils Wagner; Scott Dieteren; Niklas Franz; Kernt Köhler; Katharina Mörs; Luka Nicin; Julia Schmidt; Mario Perl; Ingo Marzi; Borna Relja Journal: PLoS One Date: 2018-02-08 Impact factor: 3.240