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Protective effects of chlorogenic acid on acute hepatotoxicity induced by lipopolysaccharide in mice

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Abstract

Objective and design

To investigate the potential protective effects of chlorogenic acid (CGA) on acute liver injury caused by lipopolysaccharide (LPS) in mice.

Materials and methods

C57BL/6J mice were pretreated with CGA (50 mg/kg, intraperitoneally) once per day for 5 days before an overnight LPS challenge (30 mg/kg, intraperitoneally). Severity of liver injury was assessed by histological analysis and determination of serum ALT and AST levels. Expression and activation of key regulators involved in the inflammatory response were determined, respectively, by real-time RT-PCR and western blotting.

Results

In contrast to the yellow color of the liver in LPS-treated mice, CGA maintained the normal reddish appearance of the liver. Histological analysis indicated that CGA attenuated the infiltration of neutrophil cells and the necrosis of hepatocytes. CGA also decreased the elevated plasma levels of ALT and AST. At the transcriptional level, CGA pretreatment suppressed hepatic mRNA expression of toll-like receptor 4 (TLR4), TNF-α and NF-κB p65 subunit. In contrast, mRNA level of the transcriptional coactivator PGC-1α was restored by CGA. Finally, CGA reduced the phosphorylation of NF-κB p65 subunit in the liver.

Conclusion

Our data suggest that CGA has remarkable hepatoprotective effects on LPS-induced liver injury and that the possible mechanism is related to its anti-inflammatory action.

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Acknowledgments

This work was supported by grants from Chinese National Science Foundation (30870928), Major Program of Educational Commission of Jiangsu Province (09KJA180003), Nanjing Normal University Outstanding Talents Program (2008104XGQ0065), Opening Project of Jiangsu Key Laboratory for Molecular and Medical Biotechnology (MMB09KF05), Mega-projects of Science Research for the 11th Five-year Plan of China (2009ZX09302) and National Science Foundation for Talent Training in Basic Science (J0730650). The authors wish to thank Dr. Jessica Schwartz (University of Michigan) for helping to improve the English writing.

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Correspondence to Chang Liu.

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Responsible Editor: K. Visvanathan.

Y. Xu and J. Chen contributed equally to this work.

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Xu, Y., Chen, J., Yu, X. et al. Protective effects of chlorogenic acid on acute hepatotoxicity induced by lipopolysaccharide in mice. Inflamm. Res. 59, 871–877 (2010). https://doi.org/10.1007/s00011-010-0199-z

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  • DOI: https://doi.org/10.1007/s00011-010-0199-z

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