Effect of melatonin on altered expression of vasoregulatory genes during hepatic ischemia/reperfusion.
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, ET(B) 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-alpha 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.
Park
Sang-Won
SW
College of Pharmacy, Sungkyunkwan University, Suwon 440-746, Korea.
Choi
Sun-Mi
SM
Lee
Sun-Mee
SM
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D002248:Carbon Monoxide / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects*; D051547:Heme Oxygenase-1 / Q000235:genetics; D007511:Ischemia / Q000378:metabolism*; D015227:Lipid Peroxidation; D008099:Liver / Q000098:blood supply*; D008297:Male; D008550:Melatonin / Q000494:pharmacology*; D052247:Nitric Oxide Synthase Type II / Q000235:genetics; D052250:Nitric Oxide Synthase Type III / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D015424:Reperfusion; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
D014409:Tumor Necrosis Factor-alpha; D002248:Carbon Monoxide; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D051547:Heme Oxygenase-1; D000410:Alanine Transaminase; D008550:Melatonin