약학회지 (YAKHAK HOEJI)

  • 제49권4호
  • /
  • Pages.347-354
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  • 2005
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  • 0377-9556(pISSN)
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  • 2383-9457(eISSN)
대한약학회 (The Pharmaceutical Society of Korea)
권호 표지

흰쥐 뇌에서의 Lipopolysaccharide-유도 산화적 스트레스에 대한 OQ21과 Melatonin의 작용

Effect of OQ21 and Melatonin on Lipopolysaccharide-Induced Oxidative Stress in Rat Brain

  • 배미경 (이화여자대학교 약학대학) ;
  • 최신규 (이화여자대학교 약학대학) ;
  • 고문정 (이화여자대학교 약학대학) ;
  • 하헌주 (이화여자대학교 약학대학) ;
  • 김화정 (이화여자대학교 약학대학)
  • Bae Mee Kyung (Research Institute of Pharmaceutical Sciences, College of Pharmacy, Ewha Womans University) ;
  • Choi Shinkyu (Research Institute of Pharmaceutical Sciences, College of Pharmacy, Ewha Womans University) ;
  • Ko Moon-Jeong (Research Institute of Pharmaceutical Sciences, College of Pharmacy, Ewha Womans University) ;
  • Ha Hun-Joo (Research Institute of Pharmaceutical Sciences, College of Pharmacy, Ewha Womans University) ;
  • Kim Hwa-Jung (Research Institute of Pharmaceutical Sciences, College of Pharmacy, Ewha Womans University)
  • 발행 : 2005.08.01
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초록

Lipopolysaccharide (LPS) induces synthesis of several inflammatory cytokines and nitric oxide (NO). NO in brain is involved not only in the regulation of important metabolic pathways via intracellular cyclic GMP-dependent path­ways, but also in neurotoxic damage by reacting with superoxide ion leading to form peroxynitrite radical. Oxidative stress has suggested to be related to the inhibition of NO synthase/cyclic GMP pathway. OQ21 is a new fluorinated quinone compound that is recently known to have inhibitory effects on both NO synthase (NOS) and guanylyl cyclase (GC). In this study, we examined effects of OQ21, other known NOS or GC inhibitors, or an antioxidant, melatonin, on the oxidative stress produced by LPS in rat brain. Oxidative stress was observed by using the 2',7'-dichlorofluorescin diacetate to measure intra-cellular reactive oxygen species (ROS) production and by measuring the formation of thiobarbituric acid reactive substances to measure lipid peroxidation. LPS induced significant increase in both ROS produdction and lipid peroxidation in all brain regions tested (striatum, hippocampus and cortex), which were dissected 6hr after intraperitoneal administration of LPS to rats. Direct striatal injection of two NOS inhibitors, N-nitro-L-arginine methyl ester and diphenyleneiodonium, or a GC inhibitor, IH-[1,2,4]oxadiazolo[4,3-a]quinoxaline-l-one, produced no significant ROS increase. However, OQ21 enhanced ROS formation in striatal tissues from LPS-treated rats. Melatonin decreased LPS-induced ROS formation and decreased ROS formation increased by OQ21 in striatum of LPS-treated rats.

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참고문헌

  1. Dantzer, R., Bluthe, R. M., Gheusi, G., Cremona, S., Laye, S., Parnet, P. and Kelley, K. W. : Molecular basis of sickness behavior. Annals N. Y. Acad. Sci. 856, 132 (1998) https://doi.org/10.1111/j.1749-6632.1998.tb08321.x
  2. Kent, S., Bluthe, R. M., Dantzer, R., Hardwick, A. J. and Kelley, K. W. : Different receptor mechanisms mediate the pyrogenic and behavioral effects of interleukin-l. Proc. Natl. Acad. Sci. USA 89, 9117 (1992)
  3. Kent, S., Kelly, K. W. and Dantzer, R. : Effects fo lipopolysaccharide on food-motivated behavior are not blocked by an interleukin-1 receptor antagonist. Neurosci. Let. 145, 83 (1992) https://doi.org/10.1016/0304-3940(92)90209-P
  4. Kent, S. R. M. and Bluthe, K. W. : Sickness behavior as a new target for drug development. Trends Pharmcol. Sci. 13, 24 (1992) https://doi.org/10.1016/0165-6147(92)90012-U
  5. Saper, C. B. : Neurobiological basis of fever. Annals N. Y. Acad. Sci. 856, 90 (1998) https://doi.org/10.1111/j.1749-6632.1998.tb08317.x
  6. Boloanos, J. P., Almeida, A., Stewart, V., Peuchen, S., Land, J. M., Clark, J. B. and Heales, S. J. R. : Nitric oxide-mediated mitochondrial damage in the brain: Mechanisms and implications for neurodegenerative diseases. J. Neurochem. 68, 2227 (1997) https://doi.org/10.1046/j.1471-4159.1997.68062227.x
  7. Halliwell, B. : How to charactrize a biological antioxidant. Free Radic. Res. Commun. 9, 1 (1990) https://doi.org/10.3109/10715769009148569
  8. Knight, J. A. : The process and theories of aging. Ann. Clin. Lab. Sci. 25, 1 (1995)
  9. Koedel, U. and Pfister, H. W. : Oxidative stress in bacterial meningitis. Brain Phathology 9, 57 (1999)
  10. Inoue, S. and Kawanishi, S. : Oxidative DNA damage induced by simultaneous generation of nitric oxide and superoxide. FEBES Lett. 371, 86 (1995) https://doi.org/10.1016/0014-5793(95)00873-8
  11. Izumi, Y., Benz, A. M., Clifford, D. B. and Zorumski, C. F. : Nitric oxide inhibitors attenuate ischemic degeneration in the CAl region of rat hippocampal slices. Neurosci. Lett. 210, 157 (1996) https://doi.org/10.1016/0304-3940(96)12669-0
  12. Love, S. : Oxidative stress in brain ischemia. Brain Phathology 9, 119 (1999)
  13. Sewerynek, E., Poeggeier, B., Melchiorri, D. and Reiter, R. J. : $H_2O_2$-induced lipid peroxidation in rat brain homogenates is greatly reduced by melatonin. Neurosci. Lett. 195, 203 (1995) https://doi.org/10.1016/0304-3940(95)11803-5
  14. Arteel, G. E., Kadiiska, M. B., Rusyn, I., Bradford, B. U., Mason, R. P., Raleigh, J. A. and Thurman, R. G. : Oxidative stress occurs in perfused rat liver at low oxygen tension by mechanisms involving peroxynitrite. Molecular Pharmacology 55, 708 (1999)
  15. Bluthe, R. M., Walter, V., Parnet, P., Laye, S., Lestage, J., Verrier, D., Poole, S., Stenning, B. E., Kelley, K. W. and Dantzer, R. : Lipopolysaccharide induce sickness behavior in rats by a vagal mediated mechnism. C. R. Acad. Sci. (Paris) 317, 499 (1994)
  16. Laye, S., Parnet, P., Goujon, E. and Dantzer, R. : Peripheral administration of lipopolysaccharide induces the expression of cytokine transcripts in the brain and pituitary of mice. Mol. Brain Res. 27, 157 (1994) https://doi.org/10.1016/0169-328X(94)90197-X
  17. Mccann, S. M., Kimura, M., Karanth, S., Yu, W. H. and Rettori, V. : Role of nitric oxide in the neuroendocrine responses to cytokines. Annals N. Y. Acad. Sci. 840, 174 (1998) https://doi.org/10.1111/j.1749-6632.1998.tb09561.x
  18. Isaac, J. T., Oliet, S. H., Hjelmstad, G. O., Nicoll, R A. and Malenka, R. C. : Expression mechanisms of long-term potentiation in the hippocampus. J. Physiol. (Paris) 90, 299 (1996) https://doi.org/10.1016/S0928-4257(97)87901-6
  19. Huang, P. L., Huang, Z., Mashimo, H., Bloch, K. D., Moskowitz, M. A., Bevan, J. A. and Fishman, M. C. : Hypertension in mice lacking the gene for endothelial nitric oxide synthase. Nature 377, 239 (1995) https://doi.org/10.1038/377239a0
  20. Melchiorri, D. and Reiter, R. J. : Paraquat toxicity and oxidative damage Reduction by melatonin. Biochem. Phamacol. 51, 1095 (1996) https://doi.org/10.1016/0006-2952(96)00055-X
  21. Sewerynek, E. and Reiter, R. J. : Oxidative damage in the liver induced by ischemia-reperfusion:protection by melatonin. Hepato-Gastroenterolog 43, 898 (1996)
  22. Sewerynek, E., Abe, M., Reiter, R. J., Barlow-Walden, L. R., Chen, L. D. McCabe, T. J., Roman, L. J. and Dias-Lopez, B. : Melatonin administration prevents lipopolysaccharide-induced oxidative damage phenobarbital-treated animals. J. Cell. Biochem. 58, 436 (1995) https://doi.org/10.1002/jcb.240580406
  23. Sewerynek, E., Melchiorri, D., Chen, L. and Reiter, R. J. : Melatonin reduces both basal and bacterial lipopolysaccharide-induced lipid peroxidation in vitro. Free R. B. M. 19, 903 (1995) https://doi.org/10.1016/0891-5849(95)00101-3
  24. David, J. C., Currie, R. W. and Robertson, H. A. : Expression and distribution of hsp71 and hsc73 messenger RNAs in rat brain following heat shock: Effect of dizocilpine maleate. Neuroscience 62, 945 (1994) https://doi.org/10.1016/0306-4522(94)90485-5
  25. Poeggeler, B., Saarela, S., Reiger, R. J., Tan, D. X., Manchester, L. C. and Barlow-Warden, L. R. : Melatonin-a highly potent endogenous radical scavenger and electron donor; new aspects of the oxidation chemistry of this indole accessed in vitro. Ann. N. Y. Acad. Sci. 738, 419 (1994) https://doi.org/10.1111/j.1749-6632.1994.tb21831.x
  26. Lee, J. A., Jung, S. R., Bae, M. K., Ryu, C. K., Lee, J. Y., Chung, J. Y., Chung, J. H. and Kim, R. J. : Pharmacological effects of novel quinone compounds, 6-(fluorinated-phenyl)amino-5,8-quinolinediones, on inhibition of drug-induced relaxation of rat aorta and their putative action mechanism. General Pharmacology 34, 33 (2000) https://doi.org/10.1016/S0306-3623(00)00044-6
  27. Keston, A. S. and Brandt, R. : The fluorometric analysis of ultramicro quantities of hydrogen peroxide. Anal. Biochem. 11, 1 (1965) https://doi.org/10.1016/0003-2697(65)90034-5
  28. Bass, D. A., Parce,J. W., Dechatelet, L. R., Szejda, P., Seeds, M. C. and Thomas, M. : Flow cytometric studies of oxidative product formation by neutrophils: a graded response to membrane stimulation. J. Immunol. 130, 1910 (1983)
  29. Bauge, J. A. and Aust, S. D. : Microsomal lipid peroxidation methods. Methods in Enzymology 52, 302 (1978) https://doi.org/10.1016/S0076-6879(78)52032-6
  30. Kosugi, H., Kato, T. and Kikugawa, K. : Formation of yellow, orange, and red pigments in the reaction of Alk-2-enals with 2-thiobarbituric acid. Analytical Biochemistry 165, 456 (1987) https://doi.org/10.1016/0003-2697(87)90296-X
  31. Ohkawa, H., Ohishi, N. and Yagi, K. : Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal. Biochem. 95, 351 (1979) https://doi.org/10.1016/0003-2697(79)90738-3
  32. Lowry, E. C., Blumberg, J. M., Rhea, R. L. and Ranson, J. P. : Serum levels of orally administered penicillin. U. S. Armed Forces Med. J. 2, 265 (1951)
  33. Ghezzi, P., Saccardo, B. and Bianchi, M. : Role of reactive oxygen intermediates in hepatotoxicity of endotoxin. Immunopharmacology 12, 241 (1986) https://doi.org/10.1016/0162-3109(86)90008-1
  34. Kumagai, Y., Midorikawa, K., Nakai, Y., Yoshikawa, T. and Kushida, K. : Homma-Takeda, S. and Shimojo, N., Inhibition of nitric oxide formation and superoxide generation during reduction of LY83583 by neuronal nitric oxide synthase. Eur. J. Pharmacol. 360, 213 (1998) https://doi.org/10.1016/S0014-2999(98)00666-9
  35. Vasquez-Vivar, J., Martas, D. A. P., Hogg, N., Masters, B. S. S., Pritchard, K. A. and Kalyanaraman, B. : Endothelial nitric oxide synthase-dependent superoxide generation from adriamycin. Biochemistry 36, 11293 (1997) https://doi.org/10.1021/bi971475e