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Effect of Trolox on Altered Vasoregulatory Gene Expression in Hepatic Ischemia/Reperfusion  

Eum, Hyun-Ae (College of Pharmacy, Sungkyunkwan University)
Lee, Sun-Mee (College of Pharmacy, Sungkyunkwan University)
Publication Information
Archives of Pharmacal Research / v.27, no.2, 2004 , pp. 225-231 More about this Journal
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 peroxi-dation 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.y.
Keywords
Trolox; Ischemia/Reperfusion; Lipid peroxidation; Vasoregulatory gene expression;
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1 Atalla, S. L., Toledo-Pereyra, L. H., MacKenzie, G. H., and Cederna, J. P., Influence of oxygen-derived free radical scavengers on ischemic livers. Transplantation, 40, 584-590 (1985)   DOI   PUBMED   ScienceOn
2 Bauer, I., Wanner, G. A., Rensing, H., Alte, C., Miescher, E. A., Wolf, B., Pannen, B. H., Clemens, M. G., and Bauer, M., Expression pattern of heme oxygenase isoenzymes 1 and 2 in normal and stress-exposed rat liver. Hepatology, 27, 829-838 (1998)   DOI   ScienceOn
3 Bromont, C., Marie, C., and Bralet, J., Increased lipid peroxida-tion in vulnerable brain regions after transient forebrain ischemia in rat. Stroke, 20, 918-924(1989)   DOI   PUBMED   ScienceOn
4 Brunner, F. and Opie, L. H., Role of endothelin-A receptors in ischemic contracture and reperfusion injury. Circulation, 97, 391-398(1998)   DOI   PUBMED   ScienceOn
5 Clemens, M. G., Bauer, M., Gingalewski, C., Miescher, E., and Zhang, J. X., Hepatic intercellular communication in shock and inflammation. Shock, 2, 1-9 (1994)   DOI   PUBMED   ScienceOn
6 Fan, C., Zwacka, R. M., and Engelhardt, J. F., Therapeutic approaches for ischemia/reperfusion injury in the liver. J. Mol. Med., 77, 577-592 (1999)   DOI   ScienceOn
7 Lee, S. M., Park, M. J., Cho, T. S., and Clemens, M. G., Hepatic injury and lipid peroxidation during ischemia and reperfusion. Shock, 13, 279-284 (2000)   DOI   PUBMED   ScienceOn
8 Suematsu, M., Wakabayashi, Y., and Ishimura, Y., Gaseous monoxides: a new class of microvascular regulator in the liver. Cardiovasc. Res., 32, 679-686 (1996)   PUBMED
9 Yokoyama, Y., Baveja, R., Kresge, N., Sonin, N., Nakanishi, K., Zhang, J. X., Gitzelmann, C. A., and Clemens, M. G., Endothelin receptor remodeling induces the portal venous hyper-response to endothelin-1 following endotoxin pretreat-ment. Shock, 17, 36-40 (2002)   DOI   ScienceOn
10 Krause, S. M., Walsh, T. F., Greenlee, W. J., Ranaei, R., Williams, D. L. Jr., and Kivlighn, S. D., Renal protection by a dual $ET_{A}$/$ET_{B}$ endothelin antagonist, L-754, 142, after aortic cross-clamping in the dog. J. Am. Soc. Nephrol., 8, 1061-1071 (1997)
11 Bryan, C. L., Patefield, A. J., Cohen, D., Nielsen, J. L., Emanual, B., and Calhoon, J. H., Assessment of injury in transplanted and non-transplanted lungs after 6 h of cold storage with glutathione. J. Appl. Physiol., 67, 1231-1241 (1994)
12 Watanabe, T., Suzuki, N., Shimamoto, N., Fujino, M., and Imada, A., Contribution of endogenous endothelin to the extension of myocardial infarct size in rats. Circ. Res., 69, 370-377 (1991)   DOI   PUBMED   ScienceOn
13 Zhang, J. X., Pegoli, W., and Clemens, M. G., Endothelin-1 induces direct constriction of hepatic sinusoids. Am. J. Physiol., 266, 624-632 (1994)
14 Baud, L., Fouqueray, B., Philippe, C., and Ardaillou, R., Reactive oxygen species as glomerular autacoids. J. Am. Soc. Nephrol., 2, S132-S138 (1992)
15 Petty, M., Grisar, J. M., Dow, J., and Jong, W. D., Effects of an alpha-tocopherol analogue on myocardial ischemia and reperfusion injury in rats. Eur. J. Pharmacal., 179, 241-242 (1990)   DOI   PUBMED   ScienceOn
16 Rensing, H., Bauer, I., Zhang, J. X., Paxian, M., Pannen, B. H., Yokoyama, Y., Clemens, M. G., and Bauer, M., Endothelin-1 and heme oxygenase-1 as modulators of sinusoidal tone in the stress-exposed rat liver. Hepatology, 36, 1453-1465 (2002)   PUBMED
17 Wu, T. W., Hashimoto, N., Au, J. X., Wu, J., Mickle, D. A, and Carey, D. Trolox protects rat hepatocytes against oxyradical damage and the ischemic rat liver from reperfusion injury. Hepatology, 13, 575-580 (1991)   DOI   PUBMED
18 Ferrari, R., Oxygen-free radicals at myocardial level: effects of ischaemia and reperfusion. Adv. Exp. Med. Biol., 366, 99-111 (1994)   DOI   PUBMED
19 Muller, T. B., Haraldseth, O., Jones, R. A., Sebastiani, G., Godtliebsen, F., Lindboe, C. F., and Unsgard, G., Combined perfusion and diffusion-weighted magnetic resonance imaging in a rat model of reversible middle cerebral artery occlusion. 231 Stroke, 26, 451-457 (1995)   DOI   PUBMED   ScienceOn
20 Goda, N., Suzuki, K., Naito, M., Takeoka, S., Tsuchida, E., Ishimura, Y., Tamatani, T., and Suematsu, M., Distribution of heme oxygenase isoforms in rat liver. Topographic basis for carbon monoxide-mediated microvascular relaxation. J. Clin. Invest., 101, 604-612 (1998)   DOI   ScienceOn
21 Horie, Y., Wolf, R., Russell, J., Shanley, T. P., and Granger, D. N., Role of Kupffer cells in gut ischemia/reperfusion-induced hepatic microvascular dysfunction in mice. Hepatology, 26, 1499-1505 (1997)   DOI   ScienceOn
22 Colletti, L. M., Remick, D. G., Burtch, G. D., Kunkel, S. L., Strieter, R. M., and Campbell, D. A. Jr., Role of tumor necrosis factor-alpha in the pathophysiologic alterations after hepatic ischemia/reperfusion injury in the rat. J. Clin. Invest., 85, 1936-1943 (1990)   DOI   PUBMED   ScienceOn
23 Lopez, O. S., Hernandez, P. O., Navarro, A. J., Perez, L. G, Rodriguez, P. M., Lamas, S., and Rodriguez, P. D., Role of reactive oxygen species in the signalling cascade of cyclosporine A-mediated up-regulation of eNOS in vascular endothelial cells. Br. J Pharmacol., 124, 447-454 (1998)   DOI   ScienceOn
24 Prasad, K., Lee, P., and Kalra, J., Influence of endothelin on cardiovascular function, oxygen free radicals, and blood chemistry. Am. Heart J., 121, 178-187 (1991)   DOI   ScienceOn
25 Buege, T. A. and Aust S. D., Microsomal lipid peroxidation. Methods Enzymol., 52, 302-310 (1978)   DOI   PUBMED
26 Pannen, B. H., Bauer, M., Zhang, J., Robotham, J. L., and Clemens, M. G., A time-dependent balance between endothelins and nitric oxide regulating portal resistance after endotoxin. Am. J Physiol., 271, 1953-1961 (1996)
27 Brehe, J. E. and Burch, H. B., Enzymatic assay for glutathione. Anal. Biochem., 74, 189-197 (1978)   DOI   ScienceOn
28 Jin, M. B., Zhu, Y., Zhang, S., Ishizaki, N., Tanaka, H., Subbotin, V. M., Lee, R. G, Starzl, T. E., and Todo, S., Attenuation of ischemic liver injury by a non-selective endothelin receptor antagonist. Transplant. Proc., 29, 1335 (1997)   DOI   ScienceOn
29 Nevalainen, T. J., Arminger, L. C., and Gavin, J. B., Effects of ischaemia on vasculature. J. Mol. Cell Cardiol., 18, 7-10 (1986)   PUBMED
30 Kawase, T., Kato, S., and Lieber, C. S., Lipid peroxidation and antioxidant defense systems in rat liver after chronic ethanol feeding. Hepatology, 10, 815-821 (1989)   DOI   PUBMED
31 Sonin, N. V., Garcia-Pagan, J. C., Nakanishi, K., Zhang, J. X., and Clemens, M. G., Patterns of vasoregulatory gene expression in the liver response to ischemia/reperfusion and endotoxemia. Shock, 11, 175-179 (1999)   DOI   PUBMED   ScienceOn
32 Hayashi, H., Chaudry, I. H., Clemens, M. G., and Baue, A. E., Hepatic ischemia models for determining the effects of ATP-$MgCl_{2}$ treatment. J. Surg. Res., 40, 167-175 (1986)   DOI   ScienceOn
33 Pannen, B. H., AI-Adili, F., Bauer, M., Clemens, M. G., and Geiger, K. K., Role of endothelins and nitric oxide in hepatic reperfusion injury in the rat. Hepatology, 27, 755-764 (1998)   DOI   ScienceOn
34 Clemens, M. G., Bauer, M., Pannen, B. H,. Bauer, I., and Zhang, J. X., Remodeling of hepatic microvascular responsiveness after ischemia/reperfusion. Shock, 8, 80-85 (1997)   DOI   PUBMED   ScienceOn
35 Chun, K., Zhang J., Biewer, J. E., Ferguson, D., and Clemens, M. G., Microcirculatory failure determines lethal hepatocyte injury in ischemia/reperfused rat livers. Shock, 1, 3-9 (1994)   PUBMED