Sep 5, 2003

Edaravone, a novel free radical scavenger, prevents liver injury and mortality in rats administered endotoxin

The Journal of Pharmacology and Experimental Therapeutics
Hiroshi KonoYoshiro Matsumoto

Abstract

We postulated that a novel free radical scavenger, 3-methyl-1-phenyl-2-pyrazolin-5-one (edaravone; EDA), would attenuate inflammatory cytokine and chemokine expression in the liver after lipopolysaccharide (LPS) challenge through its antioxidant effect. Rats were administered EDA (0.3, 1.5, 3.0, 6.0, and 12.0 mg/kg) or the same volume of saline intravenously just after LPS (10 mg/kg) injection and then was continued intermittently every 2 h (five administrations in total). Survival was assessed for the next 24 h. In separate experiments, rats were sacrificed at 60 min, 90 min, 6 h, and 9 h after LPS injection. Serum and liver sections were collected for further analysis. Survival was improved by EDA in a dose-dependent manner up to 3 mg/kg, and maximum effects were observed at a dose of 3 mg/kg. After LPS injection, alanine aminotransferase levels increased significantly to about 1,250 IU/l in the vehicle-treated group, whereas values were blunted by about 80% by EDA. Furthermore, increases in 4-hydroxynonenal-modified proteins were also blunted in the liver by EDA. Moreover, mRNA expressions of macrophage infiltrating protein-2, monocyte chemoattractant protein (MCP)-1 and MCP-5 were attenuated by EDA. As a result, increases i...Continue Reading

  • References22
  • Citations47

Mentioned in this Paper

Beta-Chemokines
Necrosis
CCL15 protein, human
Neutrophil Band Cells
Endotoxemia
Tumor Necrosis Factor-alpha
Interleukin-16
Phenylmethylpyrazolone
Antioxidant Effect
Free Radicals

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