Browse > Article
http://dx.doi.org/10.5487/TR.2007.23.4.301

Hepatoprotective Effects of Paecilomyces tenuipes Against Carbon Tetrachloride-induced Toxicity in Primary Cultures of Adult Rat Hepatocytes  

Hyun, Sun-Hee (College of Natural Resources, Yeungnam University)
Jeon, Tae-Won (Bio Toxtech Incorporation)
Lee, Sang-Kyu (College of Pharmacy, Yeungnam University)
Kim, Chun-Hwa (College of Pharmacy, Yeungnam University)
Seo, Young-Min (College of Pharmacy, Yeungnam University)
Kim, Ju-Hyun (College of Pharmacy, Yeungnam University)
Jeong, He-Min (College of Pharmacy, Yeungnam University)
Kang, Mi-Jeong (College of Pharmacy, Yeungnam University)
Lee, Jae-Sung (College of Natural Resources, Yeungnam University)
Jeong, Tae-Cheon (College of Pharmacy, Yeungnam University)
Publication Information
Toxicological Research / v.23, no.4, 2007 , pp. 301-309 More about this Journal
Abstract
Paecilomyces tenuipes (PT), one of the Ascomycetes family, has been used for medicinal purposes due to its broad pharmacological activities. The present study was undertaken to investigate the hepatoprotective effects of PT water extracts against $CCl_4$-induced hepatotoxicity in primary cultures of adult rat hepatocytes. When the extract of PT was directly added into the culture medium at 1, 2, and 5 mg/ml, the extracts not only reduce the $CCl_4$-induced elevation of aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase, and lipid peroxide, but also protect cultured hepatocytes from $CCl_4$-induced reduction of reduced glutathione, glutathione reductase, glutathione-S-transferase, glutathione peroxidase, catalase and superoxide dismutase. In addition, the effects of PT water extracts on cytochrome P450 enzymes were relatively marginal, indicating that the hepatoprotective effects of PT extract against $CCl_4$-induced toxicity might not be due to the inhibition of $CCl_4$ activation. In conclusion, the PT extracts were effective in protecting against $CCl_4$ induced hepatotoxicity in hepatocyte cultures, at least in part, by scavenging free radicals, and by modulating enzyme systems involved in cellular oxidative stress.
Keywords
Paecilomyces tenuipes; Carbon tetrachloride; Cytochrome P450; Hepatocyte; Hepatotoxicity;
Citations & Related Records
연도 인용수 순위
  • Reference
1 Aebi, H. (1984). Catalase in vitro. Method. Enzymol., 105, 121-126   DOI
2 Borchers, A.T., Stern, J.S., Hackman, R.M., Keen, C.L. and Gershwin, M.E. (1999). Mushrooms, tumors, and immunity. Proc. Soc. Exp. Biol. Med., 221, 281-293
3 Brattin, W.J., Glende, E.A. Jr. and Recknagel, R.O. (1985). Pathological mechanisms in carbon tetrachloride hepatohepatotoxicity. Free Rad. Biol. Med., 1, 27-38   DOI   ScienceOn
4 Brautbar, N. and Williams, J. 2nd. (2002). Industrial solvents and liver toxicity: risk assessment, risk factors and mechanisms. Int. J. Hyg. Env. Health, 205, 479-491   DOI   ScienceOn
5 Eaton, J.W. (1991). Catalases and peroxidases and glutathione and hydrogen peroxide: mysteries of the bestiary. J. Lab. Clin. Med., 118, 3-4
6 Hatono, S., Jimenez, A. and Wargovich, M.J. (1996). Chemopreventive effects of S-allylcysteine and its relationship to the detoxification enzyme glutathione S-transferase. Carcinogenesis, 17, 1041-1044   DOI   ScienceOn
7 Kim, N.D., Kwak, M.K. and Kim, S.G. (1997). Inhibition of cytochrome P450 2E1 expression by 2-(allylthio)pyrazine, a potential chemoprotective agent: hepatoprotective effects. Biochem. Pharmacol., 53, 261-269   DOI   ScienceOn
8 Lee, S.S., Buters, J.T., Pineau, T., Fernandez-Salguero, P. and Gonzalez, F.J. (1996b). Role of CYP2E1 in the hepatotoxicity of acetaminophen. J. Biol. Chem., 271, 12063- 12067   DOI   ScienceOn
9 Ohkawa, H., Ohishi, N. and Yagi, K. (1979). Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal. Biochem., 95, 351-358   DOI   ScienceOn
10 Paglia, D.E. and Valentine, W.N. (1967). Studies on the quantitative and qualitative characterization of erythrocyte glutathione peroxidase. J. Lab. Clin. Med., 70, 158-169
11 Poli, G. (1993). Liver damage due to free radicals. Brit. Med. Bull., 49, 604-620   DOI
12 Williams, A.T. and Burk, R.F. (1990). Carbon tetrachloride hepatotoxicity: an example of free radical-mediated injury. Semin. Liver Dis., 10, 279-284   DOI   ScienceOn
13 Zangar, R.C., Benson, J.M., Burnett, V.L. and Springer, D.L. (2000). Cytochrome P450 2E1 is the primary enzyme responsible for low-dose carbon tetrachloride metabolism in human liver microsomes. Chem. Biol. Interact., 125, 233-243   DOI   ScienceOn
14 Kiho, T., Hui, J., Yamane, A. and Ukai, S. (1993). Polysaccharides in fungi. XXXII. Hypoglycemic activity and chemical properties of a polysaccharide from the cultural mycelium of Cordyceps sinensis. Biol. Pharm. Bull., 16, 1291-1293   DOI   ScienceOn
15 Hove, E.L. and Seibold, H.R. (1955). Liver necrosis and altered fat composition in vitamin E-deficient swine. J. Nutr., 56, 173-186   DOI
16 Recknagel, R.O., Glende, E.A. Jr. and Britton, R.S. (1991). Free radical damage and lipid peroxidation. In: Meeks, R.G., Harrison, S.D. and Bull, R.J. (Eds.), Hepatotoxicology. CRC Press, Florida, USA, pp. 401-436
17 Fortson, W.C., Tedesco, F.J., Starnes, E.C. and Shaw, C.T. (1985). Marked elevation of serum transaminase activity associated with extrahepatic biliary tract disease. J. Clin. Gastroenterol., 7, 502-505   DOI
18 Halliwell, B., Aeschbach, R., Loliger, J. and Aruoma, O.I. (1995). The characterization of antioxidants. Food Chem. Toxicol., 33, 601-617   DOI   ScienceOn
19 Ketterer, B. (1988). Protective role of glutathione and glutathione transferases in mutagenesis and carcinogenesis. Mutat. Res., 202, 343-361   DOI   ScienceOn
20 Carlberg, I. and Mannervik, B. (1975). Purification and characterization of the flavoenzyme glutathione reductase from rat liver. J. Biol. Chem., 250, 5475-5480
21 Jeong, H.G. (1999). Inhibition of cytochrome P450 2E1 expression by oleanolic acid: hepatoprotective effects against carbon tetrachloride-induced hepatic injury. Toxicol. Lett., 105, 215-222   DOI   ScienceOn
22 Marklund, S. and Marklund, G. (1974). Involvement of the superoxide anion radical in the autoxidation of pyrogallol and a convenient assay for superoxide dismutase. Eur. J. Biochem., 47, 469-474   DOI   ScienceOn
23 Stacey, N. and Priestly, B.G. (1978). Dose-dependent toxicity of $CCI_4$ in isolated rat hepatocytes and the effects of hepatoprotective treatments. Toxicol. Appl. Pharmacol., 45, 29-39   DOI   ScienceOn
24 Guengerich, F.P., Kim, D.H. and Iwasaki, M. (1991). Role of human cytochrome P-450 IIE1 in the oxidation of many low molecular weight cancer suspects. Chem. Res. Toxicol., 4, 168-179   DOI   ScienceOn
25 von Herbay, A., Stahl, W., Niederau, C., von Laar, J., Strohmeyer, G. and Sies, H. (1996). Diminished plasma levels of vitamin E in patients with severe viral hepatitis. Free Rad. Res., 25, 461-466   DOI
26 Comporti, M. (1985). Lipid peroxidation and cellular damage in toxic liver injury. Lab. Invest., 53, 599-623
27 Salocks, C.B., Hsieh, D.P. and Byard, J.L. (1981). Butylated hydroxytoluene pretreatment protects against cytotoxicity and reduces covalent binding of aflatoxin B1 in primary hepatocyte cultures. Toxicol. Appl. Pharmacol., 59, 331- 345   DOI   ScienceOn
28 Dickins, M. and Peterson, R.E. (1980). Effects of a hormonesupplemented medium on cytochrome P-450 content and mono-oxygenase activities of rat hepatocytes in primary culture. Biochem. Pharmacol., 29, 1231-1238   DOI   ScienceOn
29 Sedlak, J. and Lindsay, R.H. (1968). Estimation of total, protein- bound, and nonprotein sulfhydryl groups in tissue with Ellman's reagent. Anal. Biochem., 25, 192-205   DOI   ScienceOn
30 Brent, J.A. and Rumack, B.H. (1993). Role of free radicals in toxic hepatic injury. II. Are free radicals the cause of toxininduced liver injury? J. Toxicol. Clin. Toxicol., 31, 173-196   DOI   ScienceOn
31 Habig, W.H., Pabst, M.J. and Jakoby, W.B. (1974). Glutathione S-transferase. The first enzymatic step in mercapturic acid formation. J. Biol. Chem., 249, 7130-7139
32 Koop, D.R. (1986). Hydroxylation of p-nitrophenol by rabbit ethanol-inducible cytochrome P-450 isozyme 3a. Mol. Pharmacol., 29, 399-404
33 Kuo, Y.C., Tsai, W.J., Shiao, M.S., Chen, C.F. and Lin, C.Y. (1996). Cordyceps sinensis as an immunomodulatory agent. Am. J. Chinese Med., 24, 111-125   DOI   ScienceOn
34 McCay, P.B., Lai, E.K., Poyer, J.L., DuBose, C.M. and Janzen, E.G. (1984). Oxygen- and carbon-centered free radical formation during carbon tetrachloride metabolism. Observation of lipid radicals in vivo and in vitro. J. Biol. Chem., 259, 2135-2143
35 Gonzalez, F.J. (1988). The molecular biology of cytochrome P450s. Pharmacol. Rev., 40, 243-288
36 Lee, J.H., Cho, S.M., Song, K.S., Hong, N.D. and Yoo, I.D. (1996a). Characterization of carbohydrate-peptide linkage of acidic heteroglycopeptide with immuno-stimulating activity from mycelium of Phellinus linteus. Chem. Pharm. Bull., 44, 1093-1095   DOI   ScienceOn
37 Recknagel, R.O., Glende, E.A. Jr., Dolak, J.A. and Waller, R.L. (1989). Mechanisms of carbon tetrachloride toxicity. Pharmacol. Therapeut., 43, 139-154   DOI   ScienceOn
38 Lowry, O.H., Rosebrough, N.J., Farr, A.L. and Randall, R.J. (1951). Protein measurement with the Folin phenol reagent. J. Biol. Chem., 193, 265-275
39 Ames, B.N., Shigenaga, M.K. and Hagen, T.M. (1993). Oxidants, antioxidants, and the degenerative diseases of aging. Proc. Natl. Acad. Sci., U.S.A., 90, 7915-7922
40 Nam, K.S., Jo, Y.S., Kim, Y.H., Hyun, J.W. and Kim, H.W. (2001). Cytotoxic activities of acetoxyscirpenediol and ergosterol peroxide from Paecilomyces tenuipes. Life Sci., 69, 229-237   DOI   ScienceOn
41 Yang, K.H., Choi, E.J. and Choe, S.Y. (1983). Cytotoxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin on primary cultures of adult rat hepatocytes. Arch. Env. Contam. Toxicol., 12, 183-188   DOI
42 Yoshikawa, T., Furukawa, Y., Murakami, M., Takemura, S. and Kondo, M. (1996). Effects of vitamin E on D-galactosamine- induced or carbon tetrachloride-induced hepatotoxicity. Digestion, 25, 222-229   DOI
43 Rahman, I., Smith, C.A., Lawson, M.F., Harrison, D.J. and MacNee, W. (1996). Induction of ã-glutamylcysteine synthetase by cigarette smoke is associated with AP-1 in human alveolar epithelial cells. FEBS Lett., 396, 21-25   DOI   ScienceOn
44 Koop, D.R. (1992). Oxidative and reductive metabolism by cytochrome P450 2E1. FASEB J., 6, 724-730   DOI