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Abstract
A novel free radical scavenger, 3-methyl-1-phenyl-2-pyrazolin-5-one (edaravone), is used for the treatment of acute ischemic stroke and is protective in several animal models of organ injury. We tested whether edaravone is protective against acute liver warm ischemia/reperfusion injury in the rat by acting as a radical scavenger. When edaravone was administered prior to ischemia and at the time of initiation of the reperfusion, liver injury was markedly reduced. Production of oxidants in the liver in this model was assessed in vivo by spin-trapping/electron spin resonance (ESR) spectroscopy. Ischemia/reperfusion caused an increase in free radical adducts rapidly, an effect markedly blocked by edaravone. Furthermore, edaravone treatment blunted ischemia/reperfusion-induced elevation in pro-inflammatory cytokines, infiltration of leukocytes and lipid peroxidation in the liver. These results demonstrate that edaravone is an effective blocker of free radicals in vivo in the liver after ischemia/reperfusion, leading to prevention of organ injury by limiting the deleterious effects of free radicals.
| Abbreviations | ||
| TNFα | = | tumor necrosis factor α |
| IL | = | interleukin |
| ALT | = | alanine aminotransferase |
| ESR | = | electron spin resonance |
| HA | = | hyaluronic acid |
| ROS | = | reactive oxygen species |
| EDA | = | edaravone |
| POBN | = | α-(4-pyridyl-1-oxide)-N-tert-butylnitrone |
| Abbreviations | ||
| TNFα | = | tumor necrosis factor α |
| IL | = | interleukin |
| ALT | = | alanine aminotransferase |
| ESR | = | electron spin resonance |
| HA | = | hyaluronic acid |
| ROS | = | reactive oxygen species |
| EDA | = | edaravone |
| POBN | = | α-(4-pyridyl-1-oxide)-N-tert-butylnitrone |