Molecular and Cellular Biochemistry

, Volume 238, Issue 1–2, pp 181–186

Schisandrin B protects against tert-butylhydroperoxide induced cerebral toxicity by enhancing glutathione antioxidant status in mouse brain

  • Kam-Ming Ko
  • Brian Y.H. Lam
Article

Abstract

Schisandrin B (Sch B), a dibenzocyclooctadiene derivative isolated from Fructus Schisandrae, has been shown to produce antioxidant effect on rodent liver and heart. A mouse model of tert-butylhydroperoxide (t-BHP) induced cerebral toxicity was adopted for examining the antioxidant potential of Sch B in the brain. Intracerebroventricular injection of t-BHP caused a time-dependent increase in mortality rate in mice. The t-BHP toxicity was associated with an increase in the extent of cerebral lipid peroxidation and an impairment in cerebral glutathione antioxidant status, as evidenced by the abrupt decrease in reduced glutathione (GSH) level and the inhibition of Se-glutathione peroxidase activity at 5 min following t-BHP challenge. Sch B pretreatment (1 or 2 mmol/kg/day × 3) produced a dose-dependent protection against t-BHP induced mortality. The protection was associated with a decrease in the extent of lipid peroxidation and an enhancement in glutathione antioxidant status in brain tissue detectable at 5 min post t-BHP challenge, with the assessed biochemical parameters being returned to normal values at 60 min in Sch B pretreated mice at a dose of 2 mmol/kg. The ensemble of results suggests the antioxidant potential of Sch B pretreatment in protecting against cerebral oxidative stress.

Schisandra chinensis schisandrin B glutathione glutathione peroxidase oxidative brain injury 

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References

  1. 1.
    State Administration of Traditional Chinese Medicine: Advanced Textbook on Traditional Chinese Medicine and Pharmacology, vol. II. New World Press, Beijing, 1995, pp 340–361Google Scholar
  2. 2.
    Chen SY, Li F: A Clinical Guide to Chinese Herbs and Formulae. Churchill Livingstone, New York, 1993, pp 169Google Scholar
  3. 3.
    Li XY: Bioactivity of neolignans from Fructus Schizandrae. Mem Inst Oswaldo Cruz 86: 31–37, 1991Google Scholar
  4. 4.
    Tang W, Esienbrand G: Chinese Drugs of Plant Origin. Springer-Verlag, Berlin, 1992, pp 903–907Google Scholar
  5. 5.
    Ip SP, Poon M KT, 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 61: 398–401, 1995Google Scholar
  6. 6.
    Yim TK, Ko KM: Schisandrin B protects against myocardial ischemiareperfusion injury by enhancing myocardial glutathione antioxidant status. Mol Cell Biochem 196: 151–156, 1999Google Scholar
  7. 7.
    Laursen SE, Belknap JK: Intracerebroventricular injections in mice –some methodological refinements. J Pharmacol Meth 16: 355–357, 1986Google Scholar
  8. 8.
    Young IS, Trimble ER: Measurement of malondialdehyde in plasma by high performance liquid chromatography with fluorimetric detection. Ann Clin Biochem 28: 504–508, 1991Google Scholar
  9. 9.
    Reed DJ, Babson JR, Beatty PW, Brodie AE, Ellis WW, Potter JW: High-performance liquid chromatography analysis of nanomole levels of glutathione, glutathione disulfide, and related thiols and disulfides. Anal Biochem 106: 56–62, 1980Google Scholar
  10. 10.
    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 52: 1687–1683, 1996Google Scholar
  11. 11.
    Lawrence RA, Burk RF: Glutathione peroxidase activity in seleniumdeficient rat liver. Biochem Biophys Res Commun 71: 952–958, 1976Google Scholar
  12. 12.
    Godin DV, Garnett ME: Species-related variations in tissue antioxidant status – I. Differences in antioxidant enzyme profiles. Comp Biochem Physiol 103: 737–742, 1992Google Scholar
  13. 13.
    Warholm M, Guthenberg C, Von Bahr C, Mannervik B: Glutathione transferases from human liver. Meth Enzymol 113: 499–504, 1985Google Scholar
  14. 14.
    Adams JD Jr, Wang B, Klaidman LK, LeBel CP, Odunze IN, Shah D: New aspects of brain oxidative stress induced by tert-butylhydroperoxide. Free Radic Biol Med 15: 195–202, 1993Google Scholar
  15. 15.
    Rush GF, Gorski JR, Ripple MG, Sowinski J, Bugelski P, Hewitt WR: Organic hydroperoxide-induced lipid peroxidation and cell death in isolated hepatocytes. Toxicol Appl Pharmacol 78: 473–483, 1985Google Scholar
  16. 16.
    Sies H, Summer KH: Hydroperoxide-metabolizing systems in rat liver. Eur J Biochem 57: 503–512, 1975Google Scholar
  17. 17.
    Jocelyn JC: Oxidation of thiols. In: J.C. Jocelyn (ed). Biochemistry of the SH Group. Academic Press, New York, 1972, pp 95–115Google Scholar
  18. 18.
    Reed DJ: Glutathione: Toxicological implications. Ann Rev Pharmacol Toxicol 30: 603–631, 1990Google Scholar
  19. 19.
    Slivka A, Mytilineoce C, Cohen G: Histochemical evaluation of glutathione in brain. Brain Res 409: 275–284, 1987Google Scholar
  20. 20.
    Wüllner U, Seyfried J, Groscurth P, Beinroth S, Winter S, Gleichmann M, Heneka M, Loschmann PA, Schulz B, Weller M, Klockgether T: Glutathione depletion and neuronal cell death: The role of reactive oxygen intermediates and mitochondrial function. Brain Res 826: 53–62, 1999Google Scholar
  21. 21.
    Smith ML, Beudek G, Dahlgrer N, Roseu I, Wieloch T, Siesjo BK: Models for studying long-term recovery following forebrain ischemia in the rat. Acta Neurol Scand 69: 385–401, 1984Google Scholar
  22. 22.
    Ochi T: Inhibition of glutathione peroxidase by tertiary-butylhydroperoxide in cultured Chinese hamster cells and the role of cellular glutathione in the recovery of activity. Toxicology 71: 119–127, 1992Google Scholar
  23. 23.
    Xue JY, Liu GT, Wei HL, Pan Y: Antioxidant activity of two dibenzocyclooctene lignans on the aged and ischemic brain in rats. Free Radic Biol Med 12: 127–135, 1992Google Scholar
  24. 24.
    Barkats M, Millecamps S, Abrioux P, Geoffroy MC, Mallet J: Overexpression of glutathione peroxidase increases the resistance of neuronal cells to Aβ-mediated neurotoxicity. J Neurochem 75: 1438–1446, 1992Google Scholar
  25. 25.
    Yamaguchi T, Sano K, Takaura K et al. for the Ebselen Study Group: Evselen in acute ischemic stroke: A placebo-controlled, double-blind clinical trial. Stroke 29: 12–17, 1998Google Scholar

Copyright information

© Kluwer Academic Publishers 2002

Authors and Affiliations

  • Kam-Ming Ko
    • 1
  • Brian Y.H. Lam
    • 1
  1. 1.Department of BiochemistryThe Hong Kong University of Science and TechnologyClear Water BayHong Kong, China

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