title: Effect of Trolox on altered vasoregulatory gene expression in hepatic ischemia/reperfusion.
abstract: This study was designed to investigate the effect of Trolox, a hydrophilic analogue of vitamin E, on the alteration of vasoregulatory gene expression during hepatic ischemia and reperfusion (I/R). Rats were subjected to 60 min of hepatic ischemia in vivo. The rats were treated intravenously with Trolox (2.5 mg/kg) or the vehicle as a control 5 min before reperfusion. Liver samples were obtained 5 h after reperfusion for a RT-PCR analysis on the mRNA for the genes of interest. These mRNA peptides are endothelin-1 (ET-1), potent vasoconstrictor peptide, its receptor ET(A) and ET(B), vasodilator endothelial nitric oxide synthase (eNOS), inducible nitric oxide synthase (iNOS), heme oxygenase-1 (HO-1), tumor necrosis factor-alpha (TNF-alpha) and cyclooxygenase-2 (COX-2). It was seen that serum alanine aminotransferase and lipid peroxidation levels were markedly increased after I/R and Trolox significantly suppressed this increase. In contrast, the glutathione concentration decreased in the I/R group, and this decrease was inhibited by Trolox. ET-1 mRNA expression was increased by I/R, an increase which was prevented by Trolox. The mRNA levels for ET(A) receptor was significantly decreased, whereas ET(B) receptor transcript increased in the I/R group. The increase in ET(A) was prevented by Trolox. The mRNA levels for iNOS and HO-1 significantly increased in the I/R group and Trolox attenuated this increase. There were no significant differences in eNOS mRNA expression among any of the experimental groups. The mRNA levels for COX-2 and TNF-alpha significantly increased in I/R group and Trolox also attenuated this increase. Our findings suggest that I/R induces an imbalanced hepatic vasoregulatory gene expression and Trolox ameliorates this change through its free radical scavenging activity.
authors.affiliation: College of Pharmacy, Sungkyunkwan University, 300 Cheoncheon-dong, Jangan-gu, Suwon-si, Gyeonggi-do 440-746, Korea.
authors.forename: Hyun-Ae
authors.initials: HA
authors.lastname: Eum
authors.forename: Sun-Mee
authors.initials: SM
authors.lastname: Lee
mesh_terms: D000410:Alanine Transaminase / Q000378:metabolism; D000818:Animals; D001808:Blood Vessels / Q000502:physiology*; D002839:Chromans / Q000494:pharmacology*; D051546:Cyclooxygenase 2; D017931:DNA Primers; D005786:Gene Expression Regulation / Q000187:drug effects*; D005978:Glutathione / Q000378:metabolism; D007527:Isoenzymes / Q000096:biosynthesis / Q000235:genetics; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000235:genetics; D014662:Vasoconstrictor Agents / Q000378:metabolism; D014665:Vasodilator Agents / Q000378:metabolism
chemical_list: D002839:Chromans; D017931:DNA Primers; D007527:Isoenzymes; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D000410:Alanine Transaminase; D005978:Glutathione; C010643:6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid