Journal of Veterinary Clinics (한국임상수의학회지)

The Korean Society of Veterinary Clinics (한국임상수의학회)
권호 표지

Protective Effect of Rutin on Carbon Tetrachloride-Induced Acute Hepatotoxicity in Rats

사염화탄소 투여로 인한 랫드의 급성 간 손상에 대한 루틴의 예방 효과

  • Hwang, Eui-Kyung (Department of Animal Science, College of Life Science and Natural Resources, Sangji University)
  • 황의경 (상지대학교 생명자원과학대학 동물자원학과)
  • Accepted : 2012.01.15
  • Published : 2013.02.28
Download PDF
⟨ Previous Next ⟩

Abstract

This study was performed to investigate hepatoprotective effect of rutin on acute hepatic damage induced by carbon tetrachloride in rats. Twenty-four male Sprague-Dawley rats were randomly divided into four groups; normal control group, $CCl_4$ control group, two rutin treatment groups (rutin 200+$CCl_4$ and rutin 400+$CCl_4$). Dissolving vehicles were applied to the rats in the normal control group. The rutin was administrated to the rats in rutin 200+$CCl_4$ and rutin 400+$CCl_4$ groups at the levels of 200 mg/kg and 400 mg/kg, 3 consecutive days orally, with 24 hours interval before inoculating $CCl_4$. $CCl_4$ was intraperitoneally administered an hour after the last treatment of rutin to the rats in every group except the normal control group. The body weight of rats in $CCl_4$ control group were significantly lower than other groups (p < 0.05), but the liver weight and relative liver weight were higher than normal control group (p < 0.05). The activities of ALT, AST, ALP, GTP, LDH and the level of total bilirubin in sera of rats in $CCl_4$ control group were higher and the levels of total protein, albumin and globulin were lower than the normal group (p < 0.05). The activities of ALT, AST, ALP, GTP, LDH and the level of total bilirubin in rutin 200+$CCl_4$ and rutin 400+$CCl_4$ groups were lower than $CCl_4$ control group (p < 0.05). Therefore the pre-treatment of rutin before $CCl_4$ inoculation in rats effectively inhibited the elevation of serum ALT, AST and total bilirubin which are the parameters of hepatic damage.

Keywords

References

  1. 김길수, 박준형. 사염화탄소에 의한 랫드의 간손상에 미치 는 인진호추출물의 영향. 1. 혈청내 효소(AST, ALT, LDH) 활성도, 지질함량 및 간내 과산화지질함량에 미치는 영향. 대한수의학회지 1992; 32: 347-356.
  2. 손홍수, 김현숙, 주진순. 루틴과 헤스페리딘이 간 독성을 일으킨 흰쥐의 cholesterol 함량, transaminase, alkaline phosphatase 효소활성에 미치는 영향. 한국농화학회지 1991; 34: 318-326.
  3. 이삼열, 정윤섭, 권오헌, 송경순. 임상병리검사법. 7판. 서 울: 연세대학교 출판부. 2000: 224-315.
  4. 임교환, 어성국, 김영소, 이종길, 한성순. 천연 Rutin의 항 균효과와 급성독성에 미치는 영향. 생약학회지 1996; 27: 309-315.
  5. 임미경, 김주완, 김지은, 김홍태, 정상주, 강미영, 이근우. 헛개나무추출액 및 생약성분의 혼용이 사염화탄소 투여로 유발된 흰쥐의 급성 간 및 신장손상의 회복에 미치는 영 향. 한국임상수의학회지 2007; 24: 400-405.
  6. 황의경. 루틴 첨가가 고지방 식이 랫드의 혈청 지질 농도 의 변화에 미치는 영향. 한국임상수의학회지 2008; 25: 324-329.
  7. Chen SS, Gong J, Liu FT, Mahammed U. Naturally occurring polyphenolic antioxidants modulate IgE-mediated mast cell activation. Immunology 2000; 100: 471-480. https://doi.org/10.1046/j.1365-2567.2000.00045.x
  8. Choi H, Joeng D, Jung B, Shin T, Wie M. Phenidone, a dual inhibitor of cyclooxygenase and lipoxygenase, inhibits carbon tetrachloride-induced acute liver injury in rats. Korean J vet Res 2010; 50: 145-149.
  9. Cook NC, Samman S. Flavonoids-Chemistry, metabolism, cardioprotective effects, and dietary sources. J Nutr Biochem 1996; 7: 66-76. https://doi.org/10.1016/0955-2863(95)00168-9
  10. Di Carlo G, Mascolo N, Izzo AA, Capasso F. Flavonoids: Old and new aspects of a class of natural therapeutic drugs. Life Sci 1999; 65: 337-353. https://doi.org/10.1016/S0024-3205(99)00120-4
  11. Erlund I. Review of the flavonoids quercetin, hesperetin, and naringenin. Dietary sources, bioactivities, bioavailability, and epidemiology. Nutr Res 2004; 24: 851-874. https://doi.org/10.1016/j.nutres.2004.07.005
  12. Farber JL, El-Mofty SK. The biochemical pathology of liver cell necrosis. Am J Pathol 1975; 8: 237-250.
  13. Galati EM, Mondello MR, Lauriano ER, Taviano MF, Galluzzo M, Miceli N. Opuntia ficus indica (L) Mill fruit juice protects liver from carbon tetrachloride-induced injury. Phytother Res 2005; 19: 796-800. https://doi.org/10.1002/ptr.1741
  14. Gryglewski RJ, Korbut R, Robak J, wies J. On the mechanism of antithrombotic action of flavonoids. Biochem Pharmacol 1987; 36: 317-322. https://doi.org/10.1016/0006-2952(87)90288-7
  15. Guardia T, Rotelli AE, Juarez AO, Pelzer LE. Antiinflammatory properties of plant flavonoids. Effects of rutin, quercetin and hesperidin on adjuvant arthritis in rat. Il Famaco 2001; 56: 683-687. https://doi.org/10.1016/S0014-827X(01)01111-9
  16. Iwu MM, Obidoa O, Anazodo M. Biochemical mechanism of the antimalarial activity of Azadirachta indica leaf extract. Phamacol Res Commun 1986; 18: 81-91.
  17. Janakat S, Al-Merie H. Optimization of the dose and route of injection, and characterization of the time course of carbon tetrachloride-induced hepatotoxicity in the rat. J Pharmacol Toxicol Methods 2002; 48: 41-44. https://doi.org/10.1016/S1056-8719(03)00019-4
  18. Janbaz KH, Saeed SA, Gilani AH. Protective effect of rutin on paracetamol- and CCl4-induced hepatotoxicity in rodents. Fitoterapia 2002; 73: 557-563. https://doi.org/10.1016/S0367-326X(02)00217-4
  19. Kim KS, Lee NJ, You JH, Jeong YR, Yang BH, Kang JK. Protective and therapeutic effect of HSMI on CCl4 induced liver dysfunction in rats. Lab Anim Res 2007; 23: 89-94.
  20. Kim YH, Park SC, Son WY, Rhee MH, Kim TW, Han SH, Kim BH, Kim KS. Hepatoprotective effects of Opuntia humifusa against carbon tetrachloride-induced acute liver injury in rats. Lab Anim Res 2005; 21: 263-266.
  21. La Casa C, Villegas I, Alarcón de la Lastra C, Motilva V, Martin Calero MJ. Evidence for protective and antioxidant properties of rutin, a natural flavone, against ethanol induced gastric lesions. J Ethnopharmacol 2000; 71: 45-53. https://doi.org/10.1016/S0378-8741(99)00174-9
  22. Lee JS, Kim HS, Lee YJ, Yong CS, Choi HG, Han GD, Kim JA, Lee JS. Hepatoprotective effect of Grifola frondosa water extract on carbon tetrachloride-induced liver injury in rats. Food Sci Biotechnol 2008; 17: 203-207.
  23. Manach C, Scalbert A, Morand C, Remesy C, Jimenez L. Polyphenols: food and bioavailability. Am J Clin Nutr 2004; 79: 727-747. https://doi.org/10.1093/ajcn/79.5.727
  24. McGregor D, Lang M. Carbon tetrachloride: Genetic effects and other modes of action. Mutation Res 1996; 366: 181-195.
  25. Park SY, Bok SH, Jeon SM, Park YB, Lee SJ, Jeong TS, Choi MS. Effect of rutin and tannic acid supplements on cholesterol metabolism in rats. Nutr Res 2002; 22: 283-295. https://doi.org/10.1016/S0271-5317(01)00398-0
  26. Peterson J, Dwyer J. Flavonoids: Dietary occurrence and biochemical activity. Nutr Res 1998; 18: 1995-2018. https://doi.org/10.1016/S0271-5317(98)00169-9
  27. Plaa GL. Toxic responses of the liver. In: Amdur MO, Doull J, Klaassen CD(ed.). Casarett and Doull's Toxicology. 4th ed. New York: Pergamon Press. 1991: 334-353.
  28. Recknagel RO. Carbon tetrachloride hepatotoxicity. Pharmacol Rev 1967; 19: 145-208.
  29. Recknagel RO, Glende Jr EA, Dolak JA, Waller RL. Mechanisms of carbon tetrachloride toxicity. Pharmac Ther 1989; 43: 139-154. https://doi.org/10.1016/0163-7258(89)90050-8
  30. Rice-Evans CA, Miller NJ, Paganga G. Structure-Antioxidant activity relationships of flavonoids and phenolic acids. Free Radic Biol Med 1996; 20: 933-956. https://doi.org/10.1016/0891-5849(95)02227-9
  31. Robak J, Gryglewski R. Flavonoids are scavengers of superoxide anions. Biochem Phamacol 1988; 37: 837-841. https://doi.org/10.1016/0006-2952(88)90169-4
  32. Santos KFR, Oliveira TT, Nagem TJ, Pinto AS, Oliveira MGA. Hypolipidaemic effects of naringenin, rutin, nicotinic acid and their associations. Phamacol Res 1999; 40: 493-496.
  33. Silva RR, Oliveira TT, Nagem TJ, Pinto AS, Albino LFT, Almeida MR, Moraes GHK, Pinto JG. Efeito hipolipidêmico dos flavonoides naringina e rutina. Archivos Latinoamericanos de Nutrición 2001; 51: 258-264.
  34. Singh KP, Zaidi SIA, Raisuddin, Saxena AK, Dwivedi PD, Seth PK, Ray PK. Protection against carbon-tetrachlorideinduced lymphoid organotoxicity in rats by protein A. Toxicol Letters 1990; 51: 339-351. https://doi.org/10.1016/0378-4274(90)90077-Y
  35. Unde er U, Aydln S, Ba aran AA, Ba aran N. The modulating effects of quercetin and rutin on the mitomycin C induced DNA damage. Toxicol Lett 2004; 151: 143-149. https://doi.org/10.1016/j.toxlet.2003.12.071
  36. Weber LWD, Boll M, Stampfl A. Hepatotoxicity and mechanism of action of haloalkanes: Carbon tetrachloride as a toxicological model. Crit Rev Toxicol 2003; 33: 105-136. https://doi.org/10.1080/713611034
  37. Williams AT, Burk RF. Carbon tetrachloride hepatotoxicity: An example of free radical-mediated injury. Seminars Liver Dis 1990; 10: 279-284. https://doi.org/10.1055/s-2008-1040483