Molecular and Cellular Biochemistry

, Volume 293, Issue 1–2, pp 87–92 | Cite as

Schisandrin B induced antioxidant response is partly mediated by cytochrome P-4502E1 catalyzed reaction in mouse liver

  • Po Yee Chiu
  • Hoi Yan Leung
  • Michel K. T. Poon
  • Susanna S. T. Lee
  • Kam Ming Ko
Article

Abstract

In order to explore the role of cytochrome P-450 (CYP) 2E1 in schisandrin B (Sch B)-induced antioxidant and heat shock responses, the effects of Sch B treatment on hepatic mitochondrial glutathione antioxidant status (mtGAS) and heat shock protein (Hsp)25/70 expression were compared between wild-type and cyp2e1 knock-out C57B/6N mice. Cyp2e1 knock-out mice exhibited a significantly smaller degree of Sch B-induced enhancement in hepatic mtGAS when compared with the wild-type counterpart. But Hsp25/70 expression induced by Sch B was not affected. Sch B-induced enhancement of mtGAS was corroborated by the increase in hepatic mitochondrial antioxidant capacity, as assessed by in vitro measurement of oxidant production, with the enhancing effect being slightly reduced in the knock-out mice. Using liver microsomes prepared from wild-type and knock-out mice as a source of CYP, Sch B was found to be a good co-substrate for the CYP-catalyzed reaction, with the rate of NADPH oxidation observable in microsomes prepared from knock-out mice being slower. The CYP-catalyzed reaction with Sch B was associated with a concomitant production of oxidant species, with the extent of oxidant production being reduced in cyp2e1 knock-out mouse microsomes. Taken together, the results indicate that CYP2E1 is partly responsible for the hepatic metabolism of Sch B that may trigger the antioxidant response in vivo.

Key words

schisandrin B cytochrome P-450 2E1 knock-out mitochondria glutathione heat shock proteins liver 

Abbreviations

ABT

1-aminobenzotriazole

CCl4

carbon tetrachloride

CYP

cytochrome P-450

DDB

dimethyl diphenyl bicarboxylate

GAS

glutathione antioxidant status

GRD

glutathione reductase

GSH

reduced glutathione

GST

glutathione S-transferases

Hsp

heat shock protein

Sch B

schisandrin B

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Hancke JL, Burgos RA, Ahumada F: Schisandra chinensis (Turcz.) Baill. Fitoterapia 70: 451–471, 1999CrossRefGoogle Scholar
  2. 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 61: 398–401, 1995PubMedGoogle Scholar
  3. 3.
    Ko KM, Yiu HY: Schisandrin B modulates the ischemia-reperfusion induced changes in non-enzymatic antioxidant levels in isolated-perfused rat hearts. Mol Cell Biochem 220: 141–147, 2001PubMedCrossRefGoogle Scholar
  4. 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 52: 1687–1693, 1996PubMedCrossRefGoogle Scholar
  5. 5.
    Chiu PY, Ko KM: Time-dependent enhancement in mitochondrial glutathione status and ATP generation capacity by schisandrin B treatment decreases the susceptibility of rat hearts to ischemia-reperfusion injury. Biofactors 19: 43–51, 2003PubMedGoogle Scholar
  6. 6.
    Chiu PY, Tang MH, Mak DH, Poon MKT, Ko KM: Hepatoprotective mechanism of schisandrin B: role of mitochondrial glutathione antioxidant status and heat shock proteins. Free Radic Biol Med 35: 368–380, 2003PubMedCrossRefGoogle Scholar
  7. 7.
    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 77: 2887–2895, 2005PubMedCrossRefGoogle Scholar
  8. 8.
    Gonzalez FJ: The molecular biology of cytochrome P450s. Pharmacol Rev 40: 243–288, 1988PubMedGoogle Scholar
  9. 9.
    Guengerich FP, Kim DH, Iwasaki M: Role of human cytochrome P-450 IIE1 in the oxidation of many low molecular weight cancer suspects. Chem Res Toxicol 4: 168–179, 1991PubMedCrossRefGoogle Scholar
  10. 10.
    Ortiz de Montellano PR, Mathews JM: Autocatalytic alkylation of the cytochrome P-450 prosthetic haem group by 1-aminobenzotriazole. Isolation of an NN-bridged benzyne-protoporphyrin IX adduct. Biochem J 195: 761–764, 1981PubMedGoogle Scholar
  11. 11.
    Evans WH: Isolation and characterization of membranes and cell organelles. In: Rickwood D (ed). Preparative Centrifugation: A Practical Approach, Oxford University Press: New York, 1992, pp 233–270Google Scholar
  12. 12.
    Griffith OW: Determination of glutathione and glutathione disulfide using glutathione reductase and 2-vinylpyridine. Anal Biochem 106: 207–212, 1980PubMedCrossRefGoogle Scholar
  13. 13.
    Chiu PY, Mak DH, Poon MKT, Ko KM: In vivo antioxidant action of a lignan-enriched extract of Schisandra fruit and an anthraquinone-containing extract of Polygonum root in comparison with schisandrin B and emodin. Planta Med 68: 951–956, 2002PubMedCrossRefGoogle Scholar
  14. 14.
    Ip SP, Che CT, Kong YC, Ko KM: Effects of schisandrin B pretreatment on tumor necrosis factor-alpha induced apoptosis and Hsp70 expression in mouse liver. Cell Stress Chaperones 6: 44–48, 2001PubMedCrossRefGoogle Scholar
  15. 15.
    Wong FW, Chan WY, Lee SS: Resistance to carbon tetrachloride-induced hepatotoxicity in mice which lack CYP2E1 expression. Toxicol Appl Pharmacol 153: 109–118, 1998PubMedCrossRefGoogle Scholar
  16. 16.
    Lee SS, Buters JT, Pineau T, Fernandez-Salguero P, Gonzalez FJ: Role of CYP2E1 in the hepatotoxicity of acetaminophen. J Biol Chem 271: 12063–12067, 1996PubMedCrossRefGoogle Scholar
  17. 17.
    Omiecinski CJ, Remmel RP, Hosagrahara VP: Concise review of the cytochrome P450s and their roles in toxicology. Toxicol Sci 48: 151–156, 1999PubMedCrossRefGoogle Scholar
  18. 18.
    Lieber CS: Cytochrome P-4502E1: its physiological and pathological role. Physiol Rev 77: 517–44.Google Scholar
  19. 19.
    Owuor, ED, Kong AN: Antioxidants and oxidants regulated signal transduction pathways. Biochem Pharmacol 64: 765–770, 1997CrossRefGoogle Scholar
  20. 20.
    Paroo Z, Meredith MJ, Locke M, Haist JV, Karmazyn M, Noble EG: Redox signaling of cardiac HSF1 DNA binding. Am J Physiol Cell Physiol 283: C404–C411, 2002PubMedGoogle Scholar
  21. 21.
    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 205: 111–4, 2000PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science + Business Media, Inc. 2006

Authors and Affiliations

  • Po Yee Chiu
    • 1
  • Hoi Yan Leung
    • 1
  • Michel K. T. Poon
    • 1
  • Susanna S. T. Lee
    • 2
  • Kam Ming Ko
    • 1
  1. 1.Department of BiochemistryThe Hong Kong University of Science & TechnologyChina
  2. 2.Department of BiochemistryThe Chinese University of Hong KongChina

Personalised recommendations