Journal of the Korean Society of Food Science and Nutrition (한국식품영양과학회지)

The Korean Society of Food Science and Nutrition (한국식품영양과학회)
권호 표지
DOI QR코드

DOI QR Code

Hepatoprotcetive Effects of Oyster (Crassostrea gigas) Extract in a Rat Model of Alcohol-Induced Oxidative Stress

알코올로 유도된 간 손상 동물모델에서 굴 추출물의 간 보호 효과

  • Received : 2016.01.26
  • Accepted : 2016.05.23
  • Published : 2016.06.30
Download PDF
⟨ Previous Next ⟩

Abstract

This study was conducted to investigate the protective effects of water extract from Crassostrea gigas (CGW) against ethanol-induced hepatic toxicity in rats. Seventy-two male Wistar rats (6-week-old) were divided into six groups of 12 animals each: control group (1 mL saline/d), ethanol-treated group, positive control group (ethanol+Hovenia dulcis Thunb extract), CGWL group (ethanol+low dosage of CGW), CGWM group (ethanol+medium dosage of CGW), and CGWH group (ethanol+high dosage of CGW). All groups except the control group received ethanol (40% ethanol 5 g/kg) orally. CGW administration with ethanol resulted in prevention of ethanol-induced hepatotoxicity by increasing levels of serum alanine aminotransferase and ${\gamma}-glutamyltransferase$. CGW supplementation significantly reduced formation of malonaldehyde and inhibited reduction of hepatic glutathione and peroxidase levels, as compared with the ethanol-administration group. Further, CGW suppressed expression of CYP2E1, which was elevated by ethanol administration. Consequently, our results indicate that Crassostrea gigas may exert hepatoprotective effects against alcohol-induced hepatocyte injury by intensifying the anti-oxidative defense system.

본 연구는 에탄올로 유도한 알코올성 지방간 동물모델에서 굴 열수 추출물의 알코올성 간 손상 개선 효과를 평가하기 위해 수행되었다. 6주령의 SD rat(male)을 총 6개 군으로 분리하였으며, 양성대조군으로 헛개나무 열매 추출물(500 mg/kg b.w.)을 처리하였다. 6주 동안 하루 간격으로 CGW를 50, 200, 800 mg/kg b.w. 농도로 경구 투여하였으며, control군을 제외한 나머지군은 40% ethanol 5 g/kg b.w.를 6주간 투여하였다. 43일째 실험동물을 희생시켜 혈액 분석 및 간 조직의 항산화 효과 분석을 통해 에탄올로 유도한 동물모델에서 굴 열수 추출물의 알코올성 간 손상 회복 효과를 확인한 결과, 에탄올에 의해 증가한 ALT와 ${\gamma}-GT$의 수준이 CGW를 투여함으로써 유의적으로 감소하였으며, 항산화효소 활성이 증가한 것을 확인할 수 있었다. 에탄올에 의해 손상된 간 조직의 손상 정도를 평가하기 위해 수행한 조직병리학적 검사에서는 에탄올의 투여로 증가한 지방변성 비율 및 간세포 수와 같은 인자들이 굴 열수 추출물의 투여로 유의적으로 회복된 것을 확인하였다. 또한, 에탄올에 의해 증가한 CYP2E1의 발현이 굴 열수 추출물의 투여로 유의적으로 감소하였다. 이러한 연구 결과들로 보았을 때 본 실험에서 굴 추출물의 다당류 및 폴리페놀의 항산화 작용으로 알코올로 유도된 간 손상을 억제할 수 있음을 예상할 수도 있지만, 이후 추가적인 연구로 다른 활성성분의 규명과 관련 활성 기작을 탐구하고자 한다. 본 연구진은 이와 같은 결과를 바탕으로 굴 열수 추출물이 알코올성 지방간 동물모델에서 항산화 방어시스템의 강화를 통해 간 손상을 회복시킴을 확인할 수 있었고, 이러한 연구 성과들로 굴 추출물이 알코올성 간 손상 개선에 있어 효과적인 대안으로서 더욱 더 많은 분야에서 연구되기를 바라는 바이다.

Keywords

References

  1. Altamirano J, Bataller R. 2011. Alcoholic liver disease: pathogenesis and new targets for therapy. Nat Rev Gastroenterol Hepatol 8: 491-501. https://doi.org/10.1038/nrgastro.2011.134
  2. Nagata K, Suzuki H, Sakaguchi S. 2007. Common pathogenic mechanism in development progression of liver injury caused by non-alcoholic or alcoholic steatohepatitis. J Toxicol Sci 32: 453-568. https://doi.org/10.2131/jts.32.453
  3. Ceni E, Mello T, Galli A. 2004. Pathogenesis of alcoholic liver disease: role of oxidative metabolism. World J Gastroenterol 20: 17756-17772.
  4. Wu YS, Salmela KS, Lieber CS. 1998. Microsomal acetaldehyde oxidation is negligible in the presence of ethanol. Alcohol Clin Exp Res 22: 1165-1169. https://doi.org/10.1111/j.1530-0277.1998.tb03717.x
  5. Cederbaum AI. 2006. CYP2E1 - biochemical and toxicological aspects and role in alcohol-induced liver injury. Mt Sinai J Med 73: 657-672.
  6. Jones DP. 2006. Redefining oxidative stress. Antioxid Redox Signal 8: 1865-1879. https://doi.org/10.1089/ars.2006.8.1865
  7. Lieber CS. 1994. Alcohol and the liver. Gastroenterology 106: 1085-1105. https://doi.org/10.1016/0016-5085(94)90772-2
  8. Ha HL, Shin HJ, Feitelson MA, Yu DY. 2010. Oxidative stress and antioxidants in hepatic pathogenesis. World J Gastroenterol 16: 6035-6043. https://doi.org/10.3748/wjg.v16.i48.6035
  9. Yamaura K, Takahashi KG, Suzuki T. 2008. Identification and tissue expression analysis of C-type lectin and galectin in the Pacific oyster, Crassostrea gigas. Comp Biochem Physiol B Biochem Mol Biol 149: 168-175. https://doi.org/10.1016/j.cbpb.2007.09.004
  10. Shi X, Ma H, Tong C, Qu M, Jin Q, Li W. 2015. Hepatoprotective effect of a polysaccharide from Crassostrea gigas on acute and chronic models of liver injury. Int J Biol Macromol 78: 142-148. https://doi.org/10.1016/j.ijbiomac.2015.03.056
  11. Gaté L, Paul J, Ba GN, Tew KD, Tapiero H. 1999. Oxidative stress induced in pathologies: the role of antioxidants. Biomed Pharmacother 53: 169-180. https://doi.org/10.1016/S0753-3322(99)80086-9
  12. Gate L, Schultz M, Walsh E, Dhalluin S, Nguyen Ba G, Tapiero H, Tew KD. 1998. Impact of dietary supplement of Crassostrea gigas extract (JCOE) on glutathione levels and glutathione S-transferase activity in rat tissues. In Vivo 12: 299-303.
  13. Akerboom TP, Sies H. 1981. Assay of glutathione, glutathione disulfide, and glutathione mixed disulfides in biological samples. Methods Enzymol 77: 373-382. https://doi.org/10.1016/S0076-6879(81)77050-2
  14. McCord JM, Fridovich I. 1969. Superoxide dismutase. An enzymic function for erythrocuprein (hemocuprein). J Biol Chem 244: 6049-6055.
  15. Paglia DE, Valentine WN. 1967. Studies on the quantitative and qualitative characterization of erythrocyte glutathione peroxidase. J Lab Clin Med 70: 158-169.
  16. Draper HH, Hadley M. 1990. Malondialdehyde determination as index of lipid peroxidation. Methods Enzymol 186: 421-431. https://doi.org/10.1016/0076-6879(90)86135-I
  17. Jung YM, Lee SH, Lee DS, You MJ, Chung IK, Cheon WH, Kwon YS, Lee YJ, Ku SK. 2011. Fermented garlic protects diabetic, obese mice when fed a high-fat diet by antioxidant effects. Nutr Res 31: 387-396. https://doi.org/10.1016/j.nutres.2011.04.005
  18. Han JY, Lee S, Yang JH, Kim S, Sim J, Kim MG, Jeong TC, Ku SK, Cho IJ, Ki SH. 2015. Korean Red Ginseng attenuates ethanol-induced steatosis and oxidative stress via AMPK/Sirt1 activation. J Ginseng Res 39: 105-115. https://doi.org/10.1016/j.jgr.2014.09.001
  19. Bailey SM, Cunningham CC. 2002. Contribution of mitochondria to oxidative stress associated with alcoholic liver disease. Free Radical Biol Med 32: 11-16. https://doi.org/10.1016/S0891-5849(01)00769-9
  20. Whitfield JB. 2001. Gamma glutamyl transferase. Crit Rev Clin Lab Sci 38: 263-355. https://doi.org/10.1080/20014091084227
  21. Donohue TM Jr. 2007. Alcohol-induced steatosis in liver cells. World J Gastroenterol 13: 4974-4978. https://doi.org/10.3748/wjg.v13.i37.4974
  22. You M, Crabb DW. 2004. Molecular mechanisms of alcoholic fatty liver: role of sterol regulatory element-binding proteins. Alcohol 34: 39-43. https://doi.org/10.1016/j.alcohol.2004.07.004
  23. Chen YH, Yang CM, Chang SP, Hu ML. 2009. C/EBP beta and C/EBP delta expression is elevated in the early phase of ethanol-induced hepatosteatosis in mice. Acta Pharmacol Sin 30: 1138-1143. https://doi.org/10.1038/aps.2009.109
  24. Han D, Hanawa N, Saberi B, Kaplowitz N. 2006. Mechanisms of liver injury. III. Role of glutathione redox status in liver injury. Am J Physiol Gastrointest Liver Physiol 291: G1-G7. https://doi.org/10.1152/ajpgi.00001.2006
  25. Lieber CS. 1997. Cytochrome P-4502E1: its physiological and pathological role. Physiol Rev 77: 512-544.
  26. Gorsky LD, Koop DR, Coon MJ. 1984. On the stoichiometry of the oxidase and monooxygenase reactions catalyzed by liver microsomal cytochrome P-450. Products of oxygen reduction. J Biol Chem 259: 6812-6817.

Cited by

  1. 발효굴추출물의 경구 섭취가 소아 신장 성장에 미치는 효과 및 안전성 평가를 위한 무작위배정, 이중눈가림, 위약 대조 인체적용시험: 인체적용시험 프로토콜 vol.33, pp.4, 2016, https://doi.org/10.7778/jpkm.2019.33.4.37
  2. Protective Effects of the Methanol Extract from Calyx of Diospyros kaki on Alcohol-Induced Liver Injury vol.50, pp.4, 2016, https://doi.org/10.3746/jkfn.2021.50.4.339