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: Hyun-Ae Eum, Sun-Mee Lee
• Journal: Archives of pharmacal research (Arch Pharm Res) Vol. 27 Issue 2 Pg. 225-31 (Feb 2004) ISSN: 0253-6269 [Print] Korea (South)
• PMID: 15022726 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Chromans
• DNA Primers
• Isoenzymes
• RNA, Messenger
• Tumor Necrosis Factor-alpha
• Vasoconstrictor Agents
• Vasodilator Agents
• Cyclooxygenase 2
• Prostaglandin-Endoperoxide Synthases
• Alanine Transaminase
• Glutathione
• 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid

Topics

• Alanine Transaminase (metabolism)
• Animals
• Blood Vessels (physiology)
• Chromans (pharmacology)
• Cyclooxygenase 2
• DNA Primers
• Gene Expression Regulation (drug effects)
• Glutathione (metabolism)
• Isoenzymes (biosynthesis, genetics)
• Lipid Peroxidation (drug effects)
• Liver (drug effects, metabolism)
• Male
• Prostaglandin-Endoperoxide Synthases (biosynthesis, genetics)
• RNA, Messenger (biosynthesis)
• Rats
• Rats, Sprague-Dawley
• Reperfusion Injury (genetics)
• Reverse Transcriptase Polymerase Chain Reaction
• Tumor Necrosis Factor-alpha (biosynthesis, genetics)
• Vasoconstrictor Agents (metabolism)
• Vasodilator Agents (metabolism)