Protective effects of pirfenidone on D-galactosamine and lipopolysaccharide-induced acute hepatotoxicity in rats.
OBJECTIVE
To investigate the protective effects of pirfenidone on acute liver damage caused by D-galactosamine (GalN)/lipopolysaccharide (LPS) in rats.


METHODS
Sprague-Dawley rats were divided into five groups (five rats per group): normal control group, GalN/LPS-treated group, and three pirfenidone-treated group (100, 300 and 500 mg/kg i.p., respectively). All biochemical and histological indexes were determined at 12 h after GalN/LPS challenge.


METHODS
Severity of liver injury was assessed by determination of serum ALT, AST levels and histological analysis. SOD activity and MDA concentrations as well as TNF-alpha and IFN-gamma levels in the liver of rats were measured. The expression of iNOS and its product, NO concentration were also determined.


RESULTS
Pretreatment with pirfenidone significantly attenuated GalN/LPS-induced severe hepatotoxicity, as evidenced by decreased ALT, AST levels and MDA content and improved histopathological changes. Pirfenidone inhibited the elevated levels of TNF-alpha and IFN-gamma and reduced the induction of iNOS/NO in a dose-dependent manner, which might be important mechanisms related to its protective effect.


CONCLUSIONS
Pirfenidone can provide a definite protective effect against acute hepatic injury caused by GalN/LPS in rats, which may be mainly mediated through its anti-inflammatory effect.
Wang
F
F
Department of Infectious Diseases, Beijing You-an Hospital affiliated with Capital Medical University, Beijing, 100069, PR China.
Wen
T
T
Chen
X-Y
XY
Wu
H
H
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology / Q000627:therapeutic use*; D056486:Chemical and Drug Induced Liver Injury; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005688:Galactosamine / Q000633:toxicity; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D015227:Lipid Peroxidation / Q000187:drug effects; D008070:Lipopolysaccharides / Q000633:toxicity; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008107:Liver Diseases / Q000378:metabolism / Q000517:prevention & control*; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D011728:Pyridones / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012720:Severity of Illness Index
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016207:Cytokines; D008070:Lipopolysaccharides; D011728:Pyridones; D009569:Nitric Oxide; D005688:Galactosamine; C093844:pirfenidone; D052247:Nitric Oxide Synthase Type II