Environmental Analysis Health and Toxicology

환경독성보건학회 (The Korean Society of Environmental Health and Toxicology)
권호 표지

나린진(Naringin)의 $CCl_4$에 의한 급성 간독성 보호효과

Protective Effect Naringin on Carbon Tetrachloride Induced Hepatic Injury in Mice

  • 채수철 (전남대학교 생물학과) ;
  • 고은경 (전남대학교 생물학과) ;
  • 최승현 (전남대학교 생물과학.생명기술학과) ;
  • 유근창 (동신대학교 안경광학과)
  • Chae, Soo-Chul (Department of Biology, Chonnam National University) ;
  • Kho, Eun-Gyeong (Department of Biology, Chonnam National University) ;
  • Choi, Seung-Hyun (Department of Biological Sciences and Technology, Chonnam National University) ;
  • Ryu, Geun-Chang (Department of Ophthalmic Optics, Dongshin University)
  • 발행 : 2008.12.30
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초록

The protective effects of the Naringin, on carbon tetrachloride ($CCl_4$)-induced hepatotoxicity and the possible mechanisms involved in this protection were investigated in mice. Pretreatment with Naringin prior to the administration of $CCl_4$ significantly prevented an increase in serum alanine, aspartate aminotransferase activity and hepatic lipid peroxidation in a dose-dependent manner. In addition, pretreatment with Naringin also significantly prevented the depletion of glutathione (GSH) content in the livers of $CCl_4$-induced mice. However, reduced hepatic glutathione levels was unaffected by treatment with Naringin alone. In addition, Naringin prevented $CCl_4$-induced apoptosis and necrosis, as indicated by a liver DNA laddering. To determine whether caspase-8,-3 pathway involved in $CCl_4$-induced acute liver injury, caspase-8, -3 activities were tested by ELISA. Naringin attenuated $CCl_4$induced caspase-8, -3 activities in mouse livers. $CCl_4$-induced hepatotoxicity was also prevented, as indicated by a liver histopathologic study. The effects of Naringin on the cytochrome P450 (CYP) 2E1, the major isozyme involved in $CCl_4$ were also investigated. Treatment of mice with Naringin resulted in a significant decrease of the CYP2E1-dependent hydroxyl at ion and aniline in a dose-dependent manner. These findings suggest that protective effects of Naringin against the $CCl_4$-induced hepatotoxicity may be due to its ability to block CYP2E1-mediated $CCl_4$ bioactivation and that is also protects against caspase-8, -3 pathway mediated apoptosis.

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참고문헌

  1. Balestrieri ML, Castaldo D, Balestrieri C, Quagliuolo L, Giovane A and Servillo L. Modulation by flavonoids of PAF and related phospholipids in endothelial cells during oxidative stress, Journal of Lipid Research 2003; 44(2):380-387 https://doi.org/10.1194/jlr.M200292-JLR200
  2. Basu S. Carbon tetrachloride-induced lipid peroxidation: eicosanoid formation and their regulation by antioxidant nutrients, Toxicology 2003; 189: 113-127 https://doi.org/10.1016/S0300-483X(03)00157-4
  3. Benov L and Sztejnberg I. Fridovich, Critical evaluation of the use of hydroethidine as a measure of superoxide anion radical, Free Radic Biol Med 1998; 25: 826-831
  4. Berton TR, Conti CJ, Mitchell DL, Aldaz CM, Lubet RA and Fischer SM. The effect of vitamin E acetate on ultraviolet-induced mouse skin carcinogenesis, Mol Carcinog 1998; 23(3): 175-184 https://doi.org/10.1002/(SICI)1098-2744(199811)23:3<175::AID-MC6>3.0.CO;2-B
  5. Borek C. Antioxidant health effects of aged garlic extract, J Nutr 2001; 131: 1010-1015
  6. Brautbar N and Williams J. Industrial solvents and liver toxicity: risk assessment, risk factors and mechanisms, Int J Hyg Environ Health 2002; 205: 479-491 https://doi.org/10.1078/1438-4639-00175
  7. Burk RF, Trumble MJ and Lawrence RA. Rat hepatic cytosolic glutathione-dependent enzyme protection against lipid peroxidation in the NADPH-microsomal lipid peroxidation system, Biochim Biophys Acta 1980; 618(1):35-41 https://doi.org/10.1016/0005-2760(80)90051-X
  8. Chen YC, Shen SC and Lin HY. Rutinoside at C7 attenuates the apoptosis-inducing activity of flavonoids, Biochem Pharmacol 2003; 66: 1139-1150 https://doi.org/10.1016/S0006-2952(03)00455-6
  9. Cheng Z, Li Y and Chang W. Kinetic deoxyribose degradation assay and its applocation in assessing the antioxidant activities of phenolic compounds in a Fento type reaction system, Analytica Chimica Acta 2003; 478:129-139 https://doi.org/10.1016/S0003-2670(02)01435-6
  10. Choi EJ. Apoptotic signaling pathways, Exp Mol Med 2001;33: 85-95
  11. Chomczynski P and Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction, Anal Biochem 1987; 162: 156-159
  12. Cvetnic Z and Vladimir-Knezevic S. Antimicrobial activity of grapefruit seed and pulp ethanolic extract, Acta Pharmaceutica 2004; 54(3): 243-250
  13. Dicker E, McHugh T and Cederbaum A. Increased oxidation of p-nitrophenol and aniline by intact hepatocytes isolated from pyrazole-treated rats, Biochim Biophys Acta 1990; 1035: 249-256 https://doi.org/10.1016/0304-4165(90)90086-C
  14. Doostdar H, Burke MD and Mayer RT. Bioflavonoids: Selective substrated and inhibitors for cytochrome P450 CYP1A and CYP1B1, Toxicology 2000; 144: 31-38 https://doi.org/10.1016/S0300-483X(99)00215-2
  15. Dupuy J, Larrieu JF, Sutra A and Alvinerie M. Enhancement of moxidectin bioavailability in lamb by a natural flavonoid: Quercetin, Vet Parasitol 2003; 112: 337-347 https://doi.org/10.1016/S0304-4017(03)00008-6
  16. Fukao T, Hosono T, Misawa S, Seki T and Ariga T. The effects of allyl sulfides on the induction of phase II detoxification enzymes and liver injury by carbon tetrachloride, Food Chem Toxicol 2004; 42(5): 743-749 https://doi.org/10.1016/j.fct.2003.12.010
  17. Halliwell B and Gutteridge JM. The importance of free radicals and catalytic metal ions in human diseases, Mol Aspects Med 1985; 8(2): 89-193 https://doi.org/10.1016/0098-2997(85)90001-9
  18. Hidaka I, Hino K, Korenaga M, Gondo T, Nishina S, Ando M, Okuda M and Sakaida I. Stronger Neo-Minophagen C, aglycyrrhizin-containing preparation, protects liver against carbon tetrachloride-induced oxidative stress in transgenic mice expressing the hepatitis C virus polyprotein, Liver Int 2007; 27: 845-853 https://doi.org/10.1111/j.1478-3231.2007.01492.x
  19. Hodek P, Trefil P and Stiborova M. Flavonoids-potent and versatile biologically active compounds interacting with cytochromes P450, Chem Biol Interact 2002; 139: 1-21 https://doi.org/10.1016/S0009-2797(01)00285-X
  20. Igney FH and Krammer PH. Death and anti-death: tumour resistance to apoptosis, Nat Rev Cancer 2002; 2: 277-288 https://doi.org/10.1038/nrc776
  21. Jagetia GG and Reddy TK. Modulation of radiation-induced alteration in the antionxidant status of mice by naringin, Life Sciences 2005; 77(7): 780-794 https://doi.org/10.1016/j.lfs.2005.01.015
  22. Jung UJ, Lee MK, Park YB, Kang MA and Choi MS. Effects of citrus flavonois on lipid metabolism and glucoseregulating enzyme mRNA level in type-2 diabetic mice, Int J Biochem Cell Biol 2006; 38(7): 1134-1145 https://doi.org/10.1016/j.biocel.2005.12.002
  23. Kanno SI, Tomizawa A, Hiura T, Osanai Y, Shouji A, Ujibe M, Ohtake T, Kimura K and Ishikawa M. Inhibitory Effects of Naringenin on Tumor Growth in Human Cancer Cell Lines and Sarcoma S-180-Implanted Mice, Biol Pharm Bull 2005; 28(3): 527-530 https://doi.org/10.1248/bpb.28.527
  24. Kaplowitz N, Aw TY and Ookhtens M. The regulation of hepatic glutathione, Ann. Rev, Pharmacol Toxicol 1985;25: 715-744 https://doi.org/10.1146/annurev.pa.25.040185.003435
  25. Kim HO, Kim GT, Park YB, Lee M, Seo H and Choi M. Naringin alters the cholesterol biosynthsis and antioxidant enzyme activities in LDL recetpor-Knockout mice under cholesterol fed condition, Life Sci 2004; 13: 74(13), 1621-1634 https://doi.org/10.1016/j.lfs.2003.08.026
  26. Lee HU, Bae EA and Kim DH. Hepato protective effect of tectoridin and tectorigenin on tert-butyl hyperoxideinduced liver injury, J Pharmacol Sci 2005; 97: 541-544 https://doi.org/10.1254/jphs.SCZ040467
  27. Lieber CS. Aetiology and pathogenesis of alcoholic liver disease, Bail Clin Gastroent 1994; 7: 581-608
  28. Lim HY, Kim YH and Cho YH. Induction of apoptosis in the HepG2 cells by HT53, a novel natural compound isolated from Bauhinia forficata, J Molecular Microbiology and Biotechnology 2006; 16(8): 1262-1268
  29. Manibusan MK, Odin M and Eastmond DA. Postulated carbon tetrachloride mode of action, a review J Environ Sci Health C Environ Carcinog Ecotoxicol Rev 2007;25: 185-209 https://doi.org/10.1080/10590500701569398
  30. Martinez-Florez S, Gutierrez-Fernandez B, Sanchez-Campos S, Gonzalez-Gallego J and Tunon MJ. Quercetin attenuates Nuclear Factor-kappa B activation and nitric oxide production in Interleukin-1 beta-activated rat hepatocytes, J Nutr 2005; 135: 1359-1365
  31. Moron MS, Depierre JW and Mannervik B. Levels of glutathione, glutathione reductase and glutathione S-transferase activities in rat lung and liver, Biochim Biophys Acta 1979; 582(1): 67-78 https://doi.org/10.1016/0304-4165(79)90289-7
  32. Recknagel RO. Carbon tetrachloride hepatotoxicity. Pharmacol Rev 1967; 19: 145-208
  33. Recknagel RO, Glende JE, Dolak JA and Waller RL. Mechanisms of carbon tetrachloride toxicity, Pharmacol Ther 1989; 43: 139-154 https://doi.org/10.1016/0163-7258(89)90050-8
  34. Rendic S and DiCarlo FJ. Human cytochrome their reactions, substrates, inducers and inhibitors, Drug Metab Rev 1997; 29: 413-580 https://doi.org/10.3109/03602539709037591
  35. Reshef N, Hayari Y, Goren C, Boaz M, Madar Z, Knobler H. Antihypertensive effect of sweeie fruit in patients with stage I hypertension, American Journal of Hypertension, 2005; 18(10): 1360-1363 https://doi.org/10.1016/j.amjhyper.2005.05.021
  36. Riley MV. Physiologic neutralization mechanisms and the response of the corneal endothelium to hydrogen peroxide, CLAOJ 1990; 16: 16-21
  37. Seglen PO. Preparation of isolation rat liver cell, Methods Cell Biol 1976; 13: 29-83 https://doi.org/10.1016/S0091-679X(08)61797-5
  38. Sies H. Oxidative Stress, Academic Press, London 1985
  39. Singleton VL. Naturally occurring food toxicants: phenolic substances of plant origin common in foods, Adv Fd Res 1981; 27: 149-242 https://doi.org/10.1016/S0065-2628(08)60299-2
  40. Ursini F, Maiorino M, Morazzoni P, Roveri A and Pifferi G. A novel antioxidant flavonoid (IdB 1031) affecting molecular mechanisms of cellular activation, Free Radical Biology and Medicine 1994; 16: 547-553 https://doi.org/10.1016/0891-5849(94)90054-X
  41. Van Acker FA, Schouten O, Haenen GR, Van der Vijgh WJ and Bast A. Flavonoids can replace a-tocopherol as an antioxidant, FEBS Lett 2000; 473: 145-148 https://doi.org/10.1016/S0014-5793(00)01517-9
  42. Witter R and Grubbs L. The Reitman-Frankel colorimetric transminase procedure in suspected myocardial infarction, Clin Chem 1967; 13: 482
  43. Yin XM and Ding WX. Death receptor activation-induced hepatocyte apoptosis and liver injury, Curr Mol Med 2003; 3: 491-508 https://doi.org/10.2174/1566524033479555