Sodium butyrate prevents lethality of severe sepsis in rats.
This study was performed to investigate a novel strategy to pharmacologically inhibit high-mobility group box 1 protein (HMGB1) expression with sodium butyrate, a short-chain fatty acid. Using a sepsis model induced by cecal ligation and puncture (CLP), 100 male Wistar rats were randomly divided into 4 groups as follows: control group (10 rats), sham operation group (10 rats), CLP group (further randomized into 2, 6, 12, 24, 48, and 72 h post-CLP subgroups, each 10 rats), and sodium butyrate treatment group (further randomized into 12 and 24 h post-CLP subgroups, each 10 rats). Animals of all groups were killed at designated time points, and blood and tissue samples from livers, lungs, kidneys, and small intestines were harvested to determine organ damage-related variables, and HMGB1 mRNA expression was assessed by the reverse-transcription-polymerase chain reaction. In addition, we observed the effect of treatment with sodium butyrate on survival rate in septic rats. The results showed that early treatment with sodium butyrate can markedly reduce serum alanine aminotransferase, creatinine levels at 12 h, and pulmonary myeloperoxidase activity at 24 h post-CLP, and significantly improve the 1- to 6-day survival rates in animals subjected to CLP (P < 0.05-0.01). These findings suggest that HMGB1 is excessively expressed and produced in sepsis. Sodium butyrate can markedly inhibit HMGB1 mRNA expression and may have protective effect on multiple organ damage in sepsis.
Zhang
Li-Tian
LT
Department of Microbiology and Immunology, Burns Institute, First Hospital Affiliated to the PLA General Hospital (formerly 304th Hospital), Beijing, PR China.
Yao
Yong-Ming
YM
Lu
Jia-Qi
JQ
Yan
Xiao-Jian
XJ
Yu
Yan
Y
Sheng
Zhi-Yong
ZY
D006631:Amine Oxidase (Copper-Containing) / Q000378:metabolism; D000818:Animals; D002432:Cecum / Q000473:pathology; D004195:Disease Models, Animal; D005227:Fatty Acids / Q000378:metabolism; D005786:Gene Expression Regulation; D024243:HMGB1 Protein; D006609:High Mobility Group Proteins / Q000096:biosynthesis; D007422:Intestines / Q000196:embryology; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012097:Repressor Proteins / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018805:Sepsis / Q000517:prevention & control* / Q000628:therapy; D012978:Sodium Oxybate / Q000494:pharmacology*; D013997:Time Factors
D005227:Fatty Acids; D024243:HMGB1 Protein; C104200:Hbp1 protein, rat; D006609:High Mobility Group Proteins; D012097:Repressor Proteins; D012978:Sodium Oxybate; D006631:Amine Oxidase (Copper-Containing)