Korean Journal of Food Science and Technology (한국식품과학회지)

Korean Society of Food Science and Technology (한국식품과학회)
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Hepatic Protective Effect and Single-dose Toxicity Study of Water Extract of Cordyceps militaris Grown upon Protaetia dreujtarsis

굼벵이 유래 밀리타리스 동충하초 열수추출물의 간기능개선 효과 및 단회독성 평가

  • Jo, Wol-Soon (Dong-A University Medical Science Research Center, Clinical Research Center) ;
  • Nam, Byung-Hyouk (Dong-A University Medical Science Research Center, Clinical Research Center) ;
  • Oh, Su-Jung (Dong-A University Medical Science Research Center, Clinical Research Center) ;
  • Choi, Yoo-Jin (Dong-A University Medical Science Research Center, Clinical Research Center) ;
  • Kang, Eun-Young (Dong-A University Medical Science Research Center, Clinical Research Center) ;
  • Hong, Sook-Hee (Dong-A University Medical Science Research Center, Clinical Research Center) ;
  • Lee, Sang-Ho (Seogwipo Agricultral Technique Center) ;
  • Jeong, Min-Ho (Dong-A University Medical Science Research Center, Clinical Research Center)
  • 조월순 (동아대학교병원 임상시험연구센터) ;
  • 남병혁 (동아대학교병원 임상시험연구센터) ;
  • 오수정 (동아대학교병원 임상시험연구센터) ;
  • 최유진 (동아대학교병원 임상시험연구센터) ;
  • 강은영 (동아대학교병원 임상시험연구센터) ;
  • 홍숙희 (동아대학교병원 임상시험연구센터) ;
  • 이상호 (서귀포시 농업기술센터) ;
  • 정민호 (동아대학교병원 임상시험연구센터)
  • Published : 2008.02.28
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Abstract

This study was designed to evaluate the single dose toxicity and the protective effect of water extract of Cordyceps militaris grown upon Protaetia dreujtarsis (CMPD extract) on liver damage on carbon tetrachloride ($CCl_4$)- induced acute hepatotoxicity in Sprague-Dawley (SD) rats. The CMPD extract was once administered orally to both sexes of rats at dose of 2,000, 1,000 and 500 mg/kg body weight, the recommended maximum limit dose for acute toxicity. Neither significant toxic signs nor death was observed during the observation period. These results indicate that $LD_{50}$(lethal dose of 50%) of CMPD extract is greater than 2,000 mg/kg body weight in SD rats. To investigate also the effect of hepatoprotection of CMPD extract, SD rats were orally treated with CMPD extract (50, 25 and 12.5 mg/kg body weight) or silymarin (25 mg/kg body weight) before and after administration of $CCl_4$ (2 mL/kg body weight, 20% $CCl_4$ in olive oil). Treatment with CMPD extract or silymarin could decrease the GPT (glutamic-pyruvic transaminase) and GOT (glutamic-oxaloacetic transaminase) levels in serum when compared with $CCl_4$-treated group. Therefore, the results of this study show that CMPD extract can be proposed to protect the liver against $CCl_4$-induced hepatic damage in rats.

굼벵이 유래 밀리타리스 동충하초 열수추출물(CMPD extract)의 안전성 자료를 확보하기 위하여 단회경구투여 독성시험을 실시하였으며, $CCl_4$의 경구투여로 유도된 간손상 실험동물모델로부터 시험물질(CMPD extract)의 간보호효과를 확인하였다. 단회경구투여 독성시험결과, 시험물질(CMPD extract)의 최고농도(2,000mg/kg body weight)에서 독성을 나타내지 않아 $LD_{50}$ 값을 그 이상으로 결정하였다. 또한 독성물질($CCl_4$)로부터 간손상이 유발된 SD rat에 시험물질(CMPD extract)을 투여한 후 혈청으로부터 간손상과 관련한 지표물질인 GOT, GPT, TG, TC, LDL 및 HDL 활성도를 측정하였으며, 이와 함께 병리조직학적 소견을 확인하였다. 혈청 GOT는 손상군(G2)에 비해 G4, G5 시험물질투여군에서 유의한 감소를 나타내었으며, GPT의 경우 고용량 시험물질 투여군(G4)에서 유의한 감소를 나타내었다(p < 0.05). 또한 LDL 및 HDL 활성도는 손상군(G2)에 비해 유의하지는 않지만 시험 물질투여군(G4, G5, G6)에서 어느 정도 회복기미를 보였다. 병리조직학적 소견에서도 손상군(G2)의 경우 심각한 세포독성을 보였으나, 시험물질 고용량 투여군(G4)에서는 손상된 세포가 감소하였음을 확인하였다. 이상의 결과들은 굼벵이 유래 밀리타리스 동충하초 열수추출물(CMPD extract)이 $CCl_4$ 투여에 의해 유발된 급성간 손상에 대하여 간조직의 보호와 간세포의 기능유지에 유효한 물질임을 제시 하고 있다.

Keywords

References

  1. Lieber CS. Alcohol and the liver. Gastroenterology 106: 1085-1105 (1994) https://doi.org/10.1016/0016-5085(94)90772-2
  2. Lee KW, Nam BH, Jo WS, Oh SJ, Kang EY, Choi YJ, Lee JY, Cheon SC, Jeong MH, Lee JD. Collection, classification, and hepatic effect of native Cordyceps militaris. Korean J. Mycol. 34: 7-13 (2006) https://doi.org/10.4489/KJM.2006.34.1.007
  3. Brown BR, Sipes I, Sagalyn G, Ann M. Mechanisms of acute hepatic toxicity. Anesthesiology 41: 554-561 (1974) https://doi.org/10.1097/00000542-197412000-00005
  4. Goodman GA. Carbon Tetrachloride in the Pharmacological Basis of Therapeutics. Macmillan Publishing Co., New York, NY, USA. pp. 1635-1636 (1985)
  5. Ilett KF, Reid WD, Sipes IG, Krishna G. Chloroform toxicity in mice: Correlation renal and hepatic necrosis with covalent binding of metabolites to tissue macromolecules. Exp. Mol. Pathol. 19: 205-215 (1973)
  6. Shim JY, Lee YS, Lim SS, Shin KH, Hyun JE, Kim SY, Lee EB. Pharmacological activities of Paecilomyces japonica, a new type Cordyceps sp. Korean. J. Pharmacogn. 31: 163-167 (2000)
  7. Recknagel RO. Carbon tetrachloride hepatotoxicity. Pharmacol. Rev. 19: 145-208 (1967)
  8. Rechnagel RO, Glende EA. Carbon tetrachloride hepatotoxicity: An example of lethal cleavage. Crit. Rev. Toxicol. 2: 263-297 (1973) https://doi.org/10.3109/10408447309082019
  9. Villarruel MC, Diaz Gomez MI, Castro JA. The nature of the in vitro irreversible binding of carbon tetrachloride to microsomal lipids. Toxicol. Appl. Pharm. 33: 106-114 (1975) https://doi.org/10.1016/0041-008X(75)90249-5
  10. Glende EA, Pushpendran CK. Activation of phospholipase A2 by carbon tetrachloride in isolated rat hepatocytes. Biochem. Pharmacol. 35: 3301-3307 (1986) https://doi.org/10.1016/0006-2952(86)90427-2
  11. Long RM, Moore L. Inhibition of liver endoplasmic reticulum calcium pump by $CCI_4$ and release of a sequestered calcium pool. Biochem. Pharmacol. 35: 4131-4137 (1986) https://doi.org/10.1016/0006-2952(86)90687-8
  12. Plaa GL, Hewitt WR. Toxicology of the Liver. Raven Press, New York, NY, USA. pp. 103-120 (1982)
  13. Rechnagel RO. A new direction in the study of carbon tetrachloride hepatotoxicity. Life Sci. 33: 401-408 (1983)
  14. Hassan HM. Biosynthesis and regulation of superoxide dismutases. Free Radical Bio. Med. 5: 377-385 (1988) https://doi.org/10.1016/0891-5849(88)90111-6
  15. Byers T, Perry G. Dietary carotenes, vitamin C, and vitamin E as protective antioxidants in human cancers. Ann. Rev. Nutr. 12: 135-159 (1992)
  16. Nevin KG, Vijayammal PL. Effect of Aerva lanata against hepatotoxicity of carbon tetrachloride in rats. Environ. Toxicol. Phar. 20: 471-477 (2005) https://doi.org/10.1016/j.etap.2005.05.010
  17. Poli G, Gravela E, Albano E, Dianzani MU. Studies on fatty liver with isolated hepatocytes: The action of carbon tetrachloride on lipid peroxidation, protein and triglyceride synthesis and secretion. Exp. Mol. Pathol. 30: 116-127 (1979) https://doi.org/10.1016/0014-4800(79)90086-8
  18. Seakins A, Robinson DS. The effect of the administration of carbon tetrachloride on the formation of plasma lipoproteins in the rat. Biochemistry 86: 401-407 (1963) https://doi.org/10.1042/bj0860401
  19. Kim MN, Oh SW, Lee DS, Ham, SS. Antioxidative and antimutagenic effect of the ethanol extract from Cordyceps militaris. Korean J. Postharv. Sci. Technol. 8: 109-117 (2001)
  20. Koh JB, Choi MA. Effect of Cordyceps militaris on lipid metabolism in rats fed cholesterol diet. J. Food Sci. Nutr. 34: 265-270 (2001)
  21. Plaa GL. Toxic response of the liver. pp. 334-353. In: Casarett and Doull's Toxicology. Amdur MO, Doull J, Klassen CD (eds). Pergamon Press, New York, NY, USA. (1991)
  22. Hayes AW. Principles and Methods of Toxicology. Raven Press, New York, NY, USA. pp. 407-413 (1982)
  23. Teocharis SE, Margelo AP, Skaltsas SD, Spiliopoulou CA, Koutselinis AS. Induction of metallothionein in the liver of carbon tetrachloride intoxicated rats: An immuno histochemical study. Toxicology 161: 129-138 (2001) https://doi.org/10.1016/S0300-483X(01)00340-7