1. Butyrate protects liver against ischemia reperfusion injury by inhibiting nuclear factor kappa B activation in Kupffer cells.
- Author
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Qiao YL, Qian JM, Wang FR, Ma ZY, and Wang QW
- Subjects
- Animals, Cell Nucleus metabolism, Hepatitis immunology, Hepatitis metabolism, Interleukin-6 genetics, Interleukin-6 metabolism, Kupffer Cells metabolism, Liver drug effects, Liver immunology, Liver metabolism, Liver Transplantation, Male, Neutrophils immunology, Peroxidase metabolism, RNA, Messenger metabolism, Rats, Rats, Sprague-Dawley, Reperfusion Injury immunology, Reperfusion Injury metabolism, Transcription Factor RelA metabolism, Tumor Necrosis Factor-alpha genetics, Tumor Necrosis Factor-alpha metabolism, Butyrates pharmacology, Hepatitis drug therapy, Kupffer Cells drug effects, Reperfusion Injury drug therapy, Transcription Factor RelA antagonists & inhibitors, Transplantation Conditioning methods
- Abstract
Background: The inflammatory response after hepatic ischemia reperfusion (I/R) contributes to liver dysfunction and failure after transplantation. Butyrate is a four-carbon fatty acid, normally produced by bacterial fermentation of fiber in mammalian intestines, with anti-inflammatory activities. The purpose of the present study was to investigate the protective effect of butyrate preconditioning, if any, against hepatic I/R injury in rats and the underlying mechanisms involved., Methods: Male Sprague-Dawley rats were subjected to a partial (70%) hepatic ischemia for 60 min after pretreatment with either vehicle or butyrate, followed by 3, 6, and 24 h of reperfusion. Hepatic injury was evaluated by biochemical and histopathologic examinations. Neutrophil infiltration was measured by myeloperoxidase (MPO) activity. The expression of tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) was measured by enzyme-linked immunosorbent assay (Elisa) and Real-time reverse-transcriptase polymerase chain reaction (RT-PCR). The expression of nuclear factor kappa B (NF-κB) p65 was determined by immunohistochemistry and Western blot analysis., Results: Butyrate treatment markedly improved hepatic function and histology, as indicated by reduced transaminase levels and ameliorated tissue pathologic changes. The expression of tumor necrosis factor-alpha, interleukin-6, and myeloperoxidase activity was attenuated by butyrate. Butyrate also reduced I/R-induced nuclear translocation of NF-κB p65 in Kupffer cells., Conclusion: Our results suggest that butyrate alleviates I/R-induced liver injury, possibly by suppressing inflammatory factors production and preventing NF-κB activation in Kupffer cells., (Copyright © 2014. Published by Elsevier Inc.)
- Published
- 2014
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