Protective Effects of Branched-chain Amino Acid (BCAA)-enriched Corn Gluten Hydrolysates on Ethanol-induced Hepatic Injury in Rats

알코올성 간 손상을 유발한 흰쥐에 대한 고 분지아미노산 함유 옥수수 단백가수물의 간 기능 보호효과

  • Chung, Yong-Il (Department of Food and Nutrition, Hanyang University) ;
  • Bae, In-Young (Department of Food and Nutrition, Hanyang University) ;
  • Lee, Ji-Yeon (Department of Food and Nutrition, Hanyang University) ;
  • Chun, Hyang-Sook (Food Safety Research Center, Korea Food Research Institute) ;
  • Lee, Hyeon-Gyu (Department of Food and Nutrition, Hanyang University)
  • 정용일 (한양대학교 식품영양학과) ;
  • 배인영 (한양대학교 식품영양학과) ;
  • 이지연 (한양대학교 식품영양학과) ;
  • 전향숙 (한국식품연구원 안전성연구단) ;
  • 이현규 (한양대학교 식품영양학과)
  • Published : 2009.12.31

Abstract

Hepatoprotective effects of corn gluten hydrolysates (CGH) were investigated in rats orally treated with ethanol (30%(v/v), 3 g/kg body weight/day) for 4 weeks. Six-week old Sprague-Dawley male rats were divided into four dietary groups: normal diet (N), alcohol diet (E), E+CGH 1% diet (CGH-1%), and E+CGH 3% diet (CGH-3%). Body weights and liver indices were not significantly different among the four groups. However, food intakes were lower in the CGH groups than in the normal group (p<0.05). The administration of CGH significantly reduced serum alkaline phosphatase activity by 30% compared to the alcohol diet group. Among the antioxidative enzymes assessed, catalase activity was significantly decreased by 79% in the CGH diet groups compared to the alcohol diet group. In comparison to the alcohol-treated group, aldehyde dehydrogenase activity was increased by 20%, while microsomal ethanol oxidizing system activity was decreased by 20% in the CGH-treated groups. Furthermore, the area under the curve of the blood acetaldehyde concentration versus time profile after the administration of ethanol was significantly lower for the CGH rats than for the ethanol or asparaginic acid treated groups. Thus, CGH seems to offer beneficial effects by protecting against ethanol-induced hepatotoxicity by improving the acetaldehyde-related metabolizing system.

옥수수 글루텐 가수분해물(corn gluten hydrolysates, CGH)의 알코올 대사 및 간 기능 보호효과에 대한 효과를 알아보았다. 즉, 흰쥐에게 4주간 시료를 함유한 알코올을 경구투여함에 의해 간 손상을 유도시키고, 혈액 중 생화학적 간 기능 지표(ALP, GOT, GPT), 간세포 내 항산화 효소(SOD, GPX, catalase)와 지질과산화물(MDA) 및 알코올 대사와 관련된 효소(ADH, ALDH, MEOS)의 활성을 조사하였다. 또한 알코올 섭취에 따른 경시적인 ethanol과 acetaldehyde 농도에 대한 시료의 효과를 분석하였다. 알코올성 간 손상을 입은 흰쥐의 체중변화 및 간 중량에 대한 에탄올 투여 및 CGH의 효과는 보이지 않았으며, 식이섭취량은 정상군에 비해 CGH 섭취군에서 유의적으로 감소하였다. 알코올 섭취로 증가된 혈중 ALP 활성은 CGH 처치로 30% 감소한 반면, GOT 및 GPT 활성은 유의적인 변화를 보이지 않았다. 알코올성간 손상에 따른 체내 항산화 반응계 중 catalase 효소활성은 알코올 투여군에 비해 CGH 처리군에서 79%까지 유의적으로 감소하였다. ADH 활성은 유의적인 차이를 보이지 않았으나, ALDH 활성은 알코올 투여 대조군에 비해 CGH군에서 20% 정도 유의적으로 증가하였다. 특히, CGH는 MEOS활성에 대해 농도 의존적으로 작용하여 3% CGH을 급여한 그룹에서는 알코올 투여 대조군에 비해 20%까지 활성이 감소하는 결과를 보였다. 알코올 단회 투여에 따른 경시적인 혈액 중 ethanol 농도는 유의적인 차이가 없었다. 그러나 acetaldehyde 농도는 CGH 투여에 의해 급격히 감소하였고, 시간에 따른 곡선 하 면적으로 환산한 결과, 약 60% 정도 감소한 효과를 보였다. 이상과 같이, CGH는 알코올대사과정 중 ALDH 및 MEOS 활성에 작용하여 체내 알코올성 간 손상에 대한 간 기능 보호효과와 함께 ethanol 대사산물인 acetaldehyde의 체내 배출을 촉진시키는 기능성 소재로 활용이 가능함을 알 수 있었다.

Keywords

References

  1. Ramchandani VA, Bosron WF, Li TK. Research advances in ethanol metabolism. Pathol. Biol. 49: 676-682 (2001) https://doi.org/10.1016/S0369-8114(01)00232-2
  2. Lee EH, Chyun JH. Effect of $\beta$-carotene supplementation on lipid peroxide levels and antioxidative enzyme artivities in alcoholic fatty liver rats. Korean J. Nutr. 38: 289-296 (2005)
  3. Cha YS, Sachan DS. Acetyl carnitine-mediated inhibition of ethanol oxidation in hepatocytes. Alcohol 12: 289-294 (1995) https://doi.org/10.1016/0741-8329(95)00007-E
  4. Rouach H, Clement M, Ofanelli MT, Janvier B, Nordmann J, Nordmann R. Hepatic lipid peroxidation and mitochondrial susceptibility to peroxidative attacks during ethanol inhalation and withdrawal. Biochem. Biophys. Acta 753: 439-444 (1983) https://doi.org/10.1016/0005-2760(83)90068-1
  5. Peters TJ. Ethanol metabolism. Brit. Med. Bull. 38: 17-20 (1982)
  6. Pikkarainen PH, Salaspuro MP, Lieber CS. A method for the determination of free acetaldehyde in plasma. Alcohol. Clin. Exp. Res. 3: 259-261 (1979) https://doi.org/10.1111/j.1530-0277.1979.tb05311.x
  7. Umulis DM, Gurmen NM, Singh P, Fogler HS. A physiologically based model for ethanol and acetaldehyde metabolism in human beings. Alcohol 35: 3-12 (2005) https://doi.org/10.1016/j.alcohol.2004.11.004
  8. Lieber CS. Relationships between nutrition, alcohol use, and liver disease. Alcohol Res. Health 27: 220-231 (2003)
  9. Jung BS. Metabolic effects of alcohol. Korean J. Food Nutr. 4: 207-211 (1991)
  10. Rouach H, Clement M, Ofanelli MT, Janvier B, Nordmann J, Nordmann R. Hepatic lipid peroxidation and mitochondrial susceptibility to peroxidative attacks during ethanol inhalation and withdrawal. Biochem. Biophys. Acta. 753: 439-444 (1983) https://doi.org/10.1016/0005-2760(83)90068-1
  11. Moncade C, Torres V, Varghese G, Albano E, Israsel Y. Ethanolderived immuno reactive species formed by radical mechanisms. Mol. Pharmacol. 46: 786-791 (1994)
  12. Lee EH, Chyun JH. Effect of chongkukjang intake on lipid metabolism and liver function in ethanol consumed rats. Korean J. Nutr. 40: 684-692 (2007)
  13. Terpstra AHM, Hermus AJJ, West CE. Dietary protein and cholesterol metabolism in rabbits and rats. pp. 19-49 In: Current Topics in Nutrition and Disease: Animal and Vegetable Proteins in Lipid Metabolism. Alan RLiss-Inc. New York, NY, USA (1983)
  14. Lee HM, Chang UJ. Effect of corn peptide on lipid metabolism in rats. Korean J. Diet. Culture 16: 416-422 (2001)
  15. Blomstrand E, Hassmen P, Ekblom B, Newsholme EA. Administration of branched-chain amino acids during sustained exerciseeffects on performance and on plasma concentration of some amino acids. Euro. J. Appl. Physiol. 63: 58-88 (1991) https://doi.org/10.1007/BF00235174
  16. Wagenmakers AJM. Muscle amino acid metabolism at rest and during exercise: Role in human physiology and metabolism. Exerc. Sport Sci. Rev. 26: 287-314 (1998)
  17. Nihon Shokuhin Kako Co., Ltd. Peptino. pp. 1-6. In: Corn Peptide. Nihon Shokuhin Kako Co., Ltd. Tokyo, Japan (1992)
  18. Yamaguchi M, Takada M, Nozaki O, Ito M, Furukawa Y. Preparation of corn peptide from corn gluten meal and its administration effect on alcohol metabolism in stroke-prone spontaneously hypertensive rats. J. Nutr. Sci. Vitaminol. 42: 219-231 (1996) https://doi.org/10.3177/jnsv.42.219
  19. Yamaguchi M, Nishikiori F, Ito M, Furukawa Y. The effect of corn peptide ingestion on facilitating alcohol metabolism in healthy men. Biosci. Biotech. Biochem. 61: 1474-1481 (1997) https://doi.org/10.1271/bbb.61.1474
  20. Reitman S, Frankel SA. Colorimetric method for the determination of serum glutamic oxaloacetic and glutamic p$\tilde{a}$ruvic transminase. Am. J. Clin. Pathol. 28: 56-63 (1957)
  21. Winterbourn CC, Hawkins RE, Brian M, Carrell RW. The estimation of red cell superoxide dismutase activity. J. Lab. Clin. Med. 85: 337-341 (1975)
  22. Johansson LH, Hakan BLA. A spectrophotometric methods for determination of catalase activity in small tissue samples. Anal. Biochem. 174: 331-336 (1998) https://doi.org/10.1016/0003-2697(88)90554-4
  23. Flohe L, Gunzler WA. Assays of glutathione peroxidase. Method Enzymol. 105: 114-121 (1984) https://doi.org/10.1016/S0076-6879(84)05015-1
  24. Lebsack ME, Petersen DR, Collins AC, Anderson AD. Preferential inhibition of the low $K_m$ aldehyde dehydrogenase activity by pargyline. Biochem. Pharmacol. 26: 1151-1154 (1977) https://doi.org/10.1016/0006-2952(77)90060-0
  25. Shin KH, Han YN, Chung HS, Lim SS, Lee SH, Shin CS. Effects of high molecular weight fractions of aloe spp. in alcohol metabolism. Korean J. Pharmacol. 29: 120-124 (1998)
  26. Mitchell GV, Jenkins MY, Grundel E. Protein efficiency ratios and net protein ratios of selected protein foods. Plant Food Hum. Nutr. 39: 53-58 (1989) https://doi.org/10.1007/BF01092401
  27. Choi YS, Lee SY. Cholesterol-lowing effects of soybean products (curd or curd residue) in rats. J. Korean Soc. Food Sci. Nutr. 22: 673-677 (1993)
  28. Park WD, Hwang JS, Hur JW, Ahn SH, Park SK, Kwak CS. Activities of $\alpha$-D-mannosidase and $\beta$-D-mannosidase in patients with liver diseases. Korean J. Gastroenterol. 33: 211-221 (1999)
  29. Achliya GS, Wadodkar SG, Dorle AK. Evaluation of hepatoprotective effect of Amalkadi Ghrita against carbon tetrachlorideinduced hepatic damage in rats. J. Ethnopharmacol. 90: 229-232 (2004) https://doi.org/10.1016/j.jep.2003.09.037
  30. Camandola S, Aragno M, Cutrin JC, Tamagno E, Danni O, Chiarpotto E, Parola M, Leonarduzzi G, Biasi F, Poli G. Liver AP-I activation due to carbon tetrachloride is potentiated by 1,2- dibromoethane but is inhibited by a tocopherol or gadolinium chloride. Free Radical Bio. Med. 26: 1108-1116 (1999) https://doi.org/10.1016/S0891-5849(98)00298-6
  31. Gilani AH, Janbaz KH, Akhtar MS. Selective protective effect of an extract from Fumaria parviflora on paracetamol-induced hepatotoxicity. Gen. Pharmacol. 27: 979-983 (1996) https://doi.org/10.1016/0306-3623(95)02140-X
  32. Shin MK, Han SH, Park SH. Effect of soybean powder on lipid metabolism and enzyme activities in induced hyperlipidemic rats. J. East Asian Soc. Dietary Life 16: 165-173 (2006)
  33. Halliwell B, Gutteridge MC. Free Radicals in Biology and Medicine. Oxford University Press, Oxford, UK. pp. 166-170 (1985)
  34. Aebi H. Methods of Enzymatic Analysis. Academic Press, New York, NY, USA. pp. 673-684 (1974)
  35. Halliwell B. Free radical, antioxidant and human disease: Curiosity cause, or consequence? Lancet 344: 721-728 (1994) https://doi.org/10.1016/S0140-6736(94)92211-X
  36. Kim MJ, Park EM, Lee MK, Cho SY. Effect of methionine and selenium levels on alcohol metabolic enzyme system in rats. J. Korean Soc. Food Sci. Nutr. 26: 319-326 (1997)
  37. Aykac G, Usual M, Yalcin AS, Kocak-Toker N, Sivas A, Oz H. The effect of chronic ethanol ingestion in hepatic lipid peroxide, glutathione, glutathione peroxidase and glutathione transferase in rats. Toxicology 36: 71-76 (1985) https://doi.org/10.1016/0300-483X(85)90008-3
  38. Kanh BH, Son HY, Lee HS, Song SW. Reference values of hematology and serum chemistry in ktc: Sprague-Dawley rats. Korean J. Lab. Anim. Sci. 11: 141-145 (1995)
  39. Seitz HK, Simanowski UA, Garzon FT, Ridout JM, Peters TJ, Koch A, Berger MR, Einecke H, Maiwald M. Possible role of acetaldehyde in ethanol related rectal cocarcinogenesis in the rat. Gastroenterology 98: 406-413 (1990)
  40. Teschke R, Moreno F, Petrides AS. Hepatic microsomal ethanol oxidizing system (MEOS): Respective roles of ethanol and carbohydrats for the enhanced activity after chronic alcohol consumption. Biochem. Pharmacol. 30: 1745-1751 (1981) https://doi.org/10.1016/0006-2952(81)90004-6
  41. Lieber CS. The influence of alcohol on nutritional status. Nutr. Res. 46: 241-254 (1988) https://doi.org/10.1111/j.1753-4887.1988.tb05443.x
  42. Ohnishi K, Lieber CS. Reconstitution of the microsomal ethanoloxidizing system. Qualitative and quantitative changes of cytochrome P-450 after chronic ethanol consumption. J. Biol. Chem. 252: 7124-7131 (1977)
  43. Kishimoto R, Fujiwara I, Kitayama S, Goda K, Nakata Y. Changes in hepatic enzymes activities related to ethanol metabolism in mice following chronic ethanol administration. J. Nutr. Sci. Vitaminol. 41: 527-543 (1995) https://doi.org/10.3177/jnsv.41.527
  44. Koivula T, Lindros KO. Effect of long-term ethanol treatment on aldehyde and alcohol dehydrogenase activities in rat liver. Biochem. Pharmacol. 24: 1937-1942 (1975) https://doi.org/10.1016/0006-2952(75)90378-0