Protective effect of melatonin against mitochondrial injury induced by ischemia and reperfusion of rat liver

Yuji Okatani, Akihiko Wakatsuki, Russel J. Reiter, Hideaki Enzan, Yasuyo Miyahara

Research output: Contribution to journalArticlepeer-review

104 Scopus citations


Melatonin, a pineal secretory product, is a potent scavenger of a variety of free radicals. The aim of this study was to investigate the effect of melatonin on the prevention of mitochondrial injury induced by hepatic ischemia and reperfusion. Rats were subjected to 70 min of hepatic ischemia and 2 h of reperfusion. Fifteen minutes prior to ischemia and at reperfusion, animals received vehicle or melatonin (10 mg/kg body weight) intraperitoneally. In the vehicle-treated animals, the respiratory control index, ADP/O, State 3 respiration and dinitrophenol-induced uncoupled respiration decreased markedly after ischemia/reperfusion and were restored by melatonin administration. Similarly, pH change coupled with mitochondrial energy transfer was suppressed by ischemia/reperfusion with the effects being reduced by melatonin treatment. Mitochondrial lipid peroxidation was elevated in the ischemic/reperfused vehicle-treated livers, but this elevation was attenuated by melatonin. Mitochondrial glutathione peroxidase activity decreased in the vehicle-treated group with this decrease being reduced by melatonin treatment. Electron microscopic studies demonstrated that treatment with melatonin restored to near normal the ischemia/reperfusion-induced disorganization of mitochondrial structure. Melatonin protects against mitochondrial injury which reduces mitochondrial oxidative stress and improves ischemia/reperfusion-induced hepatic energy metabolism.

Original languageEnglish (US)
Pages (from-to)145-152
Number of pages8
JournalEuropean Journal of Pharmacology
Issue number1-3
StatePublished - May 23 2003


  • Antioxidant
  • Free radical
  • Ischemia/reperfusion
  • Melatonin
  • Mitochondria

ASJC Scopus subject areas

  • Pharmacology


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