Butyrate protects liver against ischemia reperfusion injury by inhibiting nuclear factor kappa B activation in Kupffer cells.
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.


CONCLUSIONS
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.
Department of General Surgery, Huashan Hospital, Fudan University, Shanghai, China.
Ying-li
YL
Qiao
Department of General Surgery, Huashan Hospital, Fudan University, Shanghai, China. Electronic address: docjimi@hotmail.com.
Jian-min
JM
Qian
Department of General Surgery, Huashan Hospital, Fudan University, Shanghai, China.
Fang-rui
FR
Wang
Department of General Surgery, Huashan Hospital, Fudan University, Shanghai, China.
Zhen-yu
ZY
Ma
Department of General Surgery, Huashan Hospital, Fudan University, Shanghai, China.
Qian-wei
QW
Wang
D000818:Animals; D002087:Butyrates / Q000494:pharmacology*; D002467:Cell Nucleus / Q000378:metabolism; D006505:Hepatitis / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D007728:Kupffer Cells / Q000187:drug effects* / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D016031:Liver Transplantation; D008297:Male; D009504:Neutrophils / Q000276:immunology; D009195:Peroxidase / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D051996:Transcription Factor RelA / Q000037:antagonists & inhibitors* / Q000378:metabolism; D019172:Transplantation Conditioning / Q000379:methods*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
D002087:Butyrates; D015850:Interleukin-6; D012333:RNA, Messenger; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha; D009195:Peroxidase
Butyrate; Kupffer cells; Myeloperoxidase; NF-κB; Reperfusion injury