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

  • Published : 2008.02.28

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.

Keywords

Cordyceps militaris;Protaetia dreujtarsis;toxicity;hepatoprotection;liver$CCl_4$

References

  1. 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)
  2. Recknagel RO. Carbon tetrachloride hepatotoxicity. Pharmacol. Rev. 19: 145-208 (1967)
  3. Rechnagel RO. A new direction in the study of carbon tetrachloride hepatotoxicity. Life Sci. 33: 401-408 (1983)
  4. 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
  5. Byers T, Perry G. Dietary carotenes, vitamin C, and vitamin E as protective antioxidants in human cancers. Ann. Rev. Nutr. 12: 135-159 (1992)
  6. 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)
  7. 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
  8. 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)
  9. 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
  10. Koh JB, Choi MA. Effect of Cordyceps militaris on lipid metabolism in rats fed cholesterol diet. J. Food Sci. Nutr. 34: 265-270 (2001)
  11. 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
  12. Lieber CS. Alcohol and the liver. Gastroenterology 106: 1085-1105 (1994) https://doi.org/10.1016/0016-5085(94)90772-2
  13. 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)
  14. 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
  15. Hayes AW. Principles and Methods of Toxicology. Raven Press, New York, NY, USA. pp. 407-413 (1982)
  16. 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
  17. 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
  18. 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
  19. Goodman GA. Carbon Tetrachloride in the Pharmacological Basis of Therapeutics. Macmillan Publishing Co., New York, NY, USA. pp. 1635-1636 (1985)
  20. 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
  21. Plaa GL, Hewitt WR. Toxicology of the Liver. Raven Press, New York, NY, USA. pp. 103-120 (1982)
  22. 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
  23. 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