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Vol. 77, No. 2, 2006
Issue release date: May 2006
Pharmacology 2006;77:63–70
(DOI:10.1159/000092773)

Effects of Schisandrin B Enantiomers on Cellular Glutathione and Menadione Toxicity in AML12 Hepatocytes

Chiu P.Y. · Leung H.Y. · Poon M.K.T. · Mak D.H.F. · Ko K.M.
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Abstract

Effects of schisandrin B enantiomer ((+)Sch B and (–)Sch B) treatment on the reduced cellular glutathione (GSH) level and susceptibility to menadione-induced toxicity were investigated and compared in AML12 hepatocytes. (+)Sch B or (–)Sch B treatment at 6.25 µmol/l produced a time-dependent change in cellular GSH level, with the maximal stimulation occurring 16 h after dosing. (+)Sch B/(–)Sch B pretreatment for 16 h dose-dependently protected against menadione toxicity, with the maximum degree of protection observable at 6.25 µmol/l and the extent of protection afforded by (–)Sch B being larger than that of (+)Sch B. The cytoprotection was associated with a parallel enhancement in cellular GSH level in both non-menadione (control) and menadione-intoxicated cells. While the GSH depletion produced by buthionine sulfoximine/phorone treatment largely abrogated the cytoprotective action of (+)Sch B/(–)Sch B, it almost completely abolished the GSH-enhancing effect of (+)Sch B and (–)Sch B in both control and menadione-treated cells. Both (+)Sch B and (–)Sch B treatments increased the GSH reductase activity in control and menadione-treated cells, with the stimulatory action of (–)Sch B being more potent than that of (+)Sch B in the control condition. (+)Sch B and (–)Sch B also enhanced the γ-glutamate cysteine ligase activity in menadione-intoxicated cells. The results indicate that (–)Sch B is more effective than (+)Sch B in enhancing cellular GSH and protecting against oxidant injury in hepatocytes.



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References

  1. Hancke JL, Burgos RA, Ahumada F: Schisandra chinensis (Turcz.) Baill Fitoterapia 1999;70:451–471.
  2. Ip SP, Poon MKT, Wu SS, Che CT, Ng KH, Kong YC, Ko KM: Effect of schisandrin B on hepatic glutathione antioxidant system in mice: protection against carbon tetrachloride toxicity. Planta Med 1995;61:398–401.
  3. Ip SP, Yiu HY, Ko KM: Schisandrin B protects against menadione-induced hepatotoxicity by enhancing DT-diaphorase activity. Mol Cell Biochem 2000;208:151–155.
  4. Ip SP, Ko KM: The crucial antioxidant action of schisandrin B in protecting against carbon tetrachloride hepatotoxicity in mice: a comparative study with butylated hydroxytoluene. Biochem Pharmacol 1996;52:1687–1693.
  5. Ip SP, Poon MKT, Che CT, Ng KH, Kong YC, Ko KM: Schisandrin B protects against carbon tetrachloride toxicity by enhancing the mitochondrial glutathione redox status in mouse liver. Free Radic Biol Med 1996;21:709–712.
  6. Chiu PY, Tang MH, Mak DHF, Poon MKT, Ko KM: Hepatoprotective mechanism of schisandrin B: role of mitochondrial glutathione antioxidant status and heat shock proteins. Free Radic Biol Med 2003;35:368–380.
  7. Ip SP, Ma CY, Che CT, Ko KM: Methylenedioxy group as determinant of schisandrin in enhancing hepatic mitochondrial glutathione in carbon tetrachloride-intoxicated mice. Biochem Pharmacol 1997;54:317–319.
  8. Ip SP, Yiu HY, Ko KM: Differential effect of schisandrin B and dimethyl diphenyl bicarboxylate (DDB) on hepatic mitochondrial glutathione redox status in carbon tetrachloride intoxicated mice. Mol Cell Biochem 2000;205:111–114.
  9. Ko KM, Poon MKT, Ip SP, Wu K: Protection against carbon tetrachloride liver toxicity by enantiomers of schisandrin B associated with differential changes in hepatic glutathione antioxidant system in mice. Pharmaceut Biol 2002;40:298–301.
  10. Dickinson DA, Forman HJ: Cellular glutathione and thiols metabolism. Biochem Pharmacol 2002;64:1019–1026.
  11. Seelig GF, Meister A: Glutathione biosynthesis: gamma-glutamylcysteine synthetase from rat kidney. Methods Enzymol 1985;113:379–390.
  12. Wu JC, Merlino G, Fausto N: Establishment and characterization of differentiated, nontransformed hepatocyte cell lines derived from mice transgenic for transforming growth factor alpha. Proc Natl Acad Sci USA 1994;91:674–678.
  13. Li PC, Mak DHF, Poon MKT, Ip SP, Ko KM: Myocardial protective effect of Sheng Mai San (SMS) and a lignan-enriched extract of Fructus schisandrae, in vivo and ex vivo. Phytomedicine 1996;3:217–221.
  14. Griffith OW: Determination of glutathione and glutathione disulfide using glutathione reductase and 2-vinylpyridine. Anal Biochem 1980;106:207–212.
  15. Chiu PY, Mak DHF, Poon MKT, Ko KM: In vivo antioxidant action in a lignan-enriched extract of schisandra fruit and an anthraquinone-containing extract of polygonum roost in comparison with schisandrin B and emodin. Planta Med 2002;68:951–956.
  16. Wu G, Fang YZ, Yang S, Lupton JR, Turner ND: Glutathione metabolism and its implications for health. J Nutr 2004;134:489–492.
  17. Monks TJ, Hanzlik RP, Cohen GM, Ross D, Graham DG: Quinone chemistry and toxicity. Toxicol Appl Pharmacol 1992;112:2–16.
  18. Morrison H, Jernstrom B, Nordenskjold M, Thor H, Orrenius S: Induction of DNA damage by menadione (2-methyl-1,4-naphthoquinone) in primary cultures of rat hepatocytes. Biochem Pharmacol 1984;33:1763–1769.
  19. Nicotera P, McConkey D, Svensson SA, Bellomo G, Orrenius S: Correlation between cytosolic Ca2+ concentration and cytotoxicity in hepatocytes exposed to oxidative stress. Toxicology 1988;52:55–63.
  20. Carlberg I, Mannervik B: Glutathione reductase. Methods Enzymol 1985;113:484–490.
  21. Filomeni G, Rotilio G, Ciriolo M: Cell signaling and the glutathione redox system. Biochem Pharmacol 2002;64:765–770.
  22. Santori G, Domenicotti C, Bellocchio A, Pronzato MA, Marinari UM, Ploi G, Cottalasso D: Effects of acute glutathione depletion induced by L-buthionine-[S[,]R]-sulfoximine on liver glucose-6-phosphatase activity. Res Commun Mol Pathol Pharmacol 1997;98:165–178.
  23. Siegers CP, Horn W, Younes M: Effect of phorone-induced glutathione depletion on the metabolism and hepatotoxicity of carbon tetrachloride and vinylidene chloride in rats. Appl Toxicol 1985;5:352–356.
  24. Tan R, Li L, Fang Q: The stereostructure of Wuweizisu B. Planta Med 1986;52:49–51.

    External Resources

  25. Li XJ, Zhao BL, Liu GT, Xin WJ: Scavenging effects on active oxygen radicals by schizandrins with different structures and configurations. Free Radic Biol Med 1990;9:99–104.
  26. Chiu PY, Mak DHF, Poon MKT, Ko KM: Role of cytochrome P-450 in schisandrin B-induced antioxidant and heat shock responses in mouse liver. Life Sci 2005;77:2887–2895.


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