Effects and mechanisms of cavidine protecting mice against LPS-induced endotoxic shock.
LPS sensitized mice are usually considered as an experimental model of endotoxin shock. The present study aims to evaluate effects of cavidine on LPS-induced endotoxin shock. Mice were intraperitoneally administrated with cavidine (1, 3 and 10mg/kg) or DEX (5mg/kg) at 1 and 12h before injecting LPS (30mg/kg) intraperitoneally. Blood samples, liver, lung and kidney tissues were harvested after LPS injection. The study demonstrated that pretreatment with cavidine reduced the mortality of mice during 72h after endotoxin injection. In addition, cavidine administration significantly attenuated histological pathophysiology features of LPS-induced injury in lung, liver and kidney. Furthermore, cavidine administration inhibited endotoxin-induced production of pro-inflammatory cytokines including TNF-α, IL-6 and HMGB1. Moreover, cavidine pretreatment attenuated the phosphorylation of mitogen-activated protein kinase primed by LPS. In summary, cavidine protects mice against LPS-induced endotoxic shock via inhibiting early pro-inflammatory cytokine TNF-α, IL-6 and late-phase cytokine HMGB1, and the modulation of HMGB1 may be related with MAPK signal pathway.
School of Pharmacy, Xi'an Jiaotong University, Xi'an, 710061, PR China. Electronic address: liwf@mail.xjtu.edu.cn.
Weifeng
W
Li
School of Pharmacy, Xi'an Jiaotong University, Xi'an, 710061, PR China.
Hailin
H
Zhang
School of Pharmacy, Xi'an Jiaotong University, Xi'an, 710061, PR China. Electronic address: niuxf@mail.xjtu.edu.cn.
Xiaofeng
X
Niu
School of Pharmacy, Xi'an Jiaotong University, Xi'an, 710061, PR China.
Xiumei
X
Wang
School of Pharmacy, Xi'an Jiaotong University, Xi'an, 710061, PR China.
Yu
Y
Wang
School of Pharmacy, Xi'an Jiaotong University, Xi'an, 710061, PR China.
Zehong
Z
He
School of Pharmacy, Xi'an Jiaotong University, Xi'an, 710061, PR China.
Huan
H
Yao
D000818:Animals; D001600:Berberine Alkaloids / Q000494:pharmacology* / Q000627:therapeutic use*; D002478:Cells, Cultured; D005260:Female; D024243:HMGB1 Protein / Q000037:antagonists & inhibitors; D007668:Kidney / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008070:Lipopolysaccharides; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D020011:Protective Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D012772:Shock, Septic / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors; D000093242:Interleukin-6 Inhibitors; D015850:Interleukin-6
D001600:Berberine Alkaloids; D024243:HMGB1 Protein; D008070:Lipopolysaccharides; D020928:Mitogen-Activated Protein Kinases; D020011:Protective Agents; D014409:Tumor Necrosis Factor-alpha; D000093242:Interleukin-6 Inhibitors; C582808:HMGB1 protein, mouse; C577686:interleukin-6, mouse; D015850:Interleukin-6; C011188:cavidine
Cavidine; Endotoxic shock; HMGB1; IL-6; TNF-α