TY - JOUR
T1 - Protective effect of melatonin against mitochondrial injury induced by ischemia and reperfusion of rat liver
AU - Okatani, Yuji
AU - Wakatsuki, Akihiko
AU - Reiter, Russel J.
AU - Enzan, Hideaki
AU - Miyahara, Yasuyo
N1 - Funding Information:
This study was supported by Research Grant 11671625 from the Ministry of Education of Japan. We would like to thank Dr. Yoshihiro Hayashi (Department of First Pathology) for his help with electron microscopic analysis.
PY - 2003/5/23
Y1 - 2003/5/23
N2 - 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.
AB - 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.
KW - Antioxidant
KW - Free radical
KW - Ischemia/reperfusion
KW - Melatonin
KW - Mitochondria
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U2 - 10.1016/S0014-2999(03)01643-1
DO - 10.1016/S0014-2999(03)01643-1
M3 - Article
C2 - 12782196
AN - SCOPUS:0038054054
SN - 0014-2999
VL - 469
SP - 145
EP - 152
JO - European Journal of Pharmacology
JF - European Journal of Pharmacology
IS - 1-3
ER -