Induction of a 72-kDa heat shock protein and protection against lipopolysaccharide-induced liver injury in cirrhotic rats.
OBJECTIVE
A 70-kDa heat shock protein (stress-inducible HSP70, HSP72) has been reported to be a cytoprotectant in a variety of organs. It has been reported that HSP72 protected non-cirrhotic rats against endotoxemia. However, its cytoprotective effect against endotoxemia in cirrhotic rats has not yet been studied. In this study, we investigated the cytoprotective effect of HSP72 on lipopolysaccharide (LPS)-induced liver injury in carbon tetrachloride (CCl(4))-induced cirrhotic rats.


METHODS
Liver cirrhosis was produced by an 8-week intraperitoneal injection of CCl(4) in male Sprague-Dawley rats. Expression of HSP72 was investigated using western blot analysis. Cirrhotic rats were given an intraperitoneal injection of LPS (10 mg/kg) with or without hyperthermia (42.5 degrees C, 15 min) preconditioning. Liver injury was assessed biochemically (aspartate transaminase, alanine transaminase, bilirubin, lactate dehydrogenase, creatinine) and histologically. The plasma tumor necrosis factor (TNF)-alpha level was determined.


RESULTS
Hyperthermia preconditioning induced a 4-fold increase in HSP72 in the cirrhotic rat liver. Pre-induction of HSP72 prevented LPS-induced liver injury, as evaluated using serum biochemical parameters and histology with reduced TNF-alpha response.


CONCLUSIONS
These findings suggest that pre-induction of HSP72 may provide therapeutic strategies for Gram-negative sepsis-induced liver injury in liver cirrhosis.
Mikami
Ken-Ichiro
K
First Department of Internal Medicine, Akita University School of Medicine, 1-1-1 Hondo, Akita City, Akita 910-8543, Japan.
Otaka
Michiro
M
Goto
Takashi
T
Miura
Kouichi
K
Ohshima
Shigetoshi
S
Yoneyama
Kazuo
K
Lin
Jiun-Guey
JG
Watanabe
Daisuke
D
Segawa
Daisuke
D
Kataoka
Ei
E
Odashima
Masaru
M
Watanabe
Sumio
S
D000818:Animals; D015153:Blotting, Western; D002251:Carbon Tetrachloride / Q000633:toxicity; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D050884:HSP72 Heat-Shock Proteins; D006360:Heat-Shock Proteins / Q000096:biosynthesis*; D006979:Hyperthermia, Induced; D008070:Lipopolysaccharides / Q000633:toxicity*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008103:Liver Cirrhosis / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012486:Salmonella typhimurium; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D050884:HSP72 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D002251:Carbon Tetrachloride