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KMID : 0043320070300121619
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Archives of Pharmacal Research
2007 Volume.30 No. 12 p.1619 ~ p.1624
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Effect of Melatonin on Altered Expression of Vasoregulatory Genes during Hepatic Ischemia/Reperfusion
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Park Sang-Won
Choi Sun-Mi
Lee Sun-Mee
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Abstract
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The production of reactive oxygen species during hepatic ischemia/reperfusion (I/R) can help create disturbances in microcirculation. This study examined the effect of melatonin, a pineal secretory product and a potent antioxidant, on the expression of vascular stress genes during hepatic I/R. Rats were subjected to 60 min of hepatic warm ischemia followed by 5 h reperfusion. Melatonin (10 mg/kg) was administered intraperitoneally 15 min before ischemia and immediately before reperfusion. The serum alanine aminotransferase and hepatic malondialdehyde levels increased markedly after I/R. These increases were significantly inhibited by melatonin. The levels of endothelin-1 (ET-1) and its receptor, ETB mRNA, were elevated by I/R but attenuated by melatonin. The mRNA levels of endothelial nitric oxide synthase (eNOS), inducible nitric oxide synthase (iNOS), and heme oxygenase-1 were significantly higher after I/ R. Melatonin augmented the increase in the eNOS mRNA level, whereas it reduced the increase in the iNOS mRNA level. The expression of tumor necrosis factor-α was increased markedly by I/R. This increase was also attenuated by melatonin. These results suggest that melatonin ameliorates the imbalanced expression of the vascular stress genes during hepatic I/R through its antioxidant property.
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KEYWORD
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Melatonin, Ischemia/Reperfusion, Microcirculation, Vasoregulatory gene expression, Oxidative stress
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