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Modulation of cytochrome P450 1 (Cyp1) by vanadium in hepatic tissue and isolated hepatocyte of C57BL/6 mice

Archives of Toxicology volume 87, pages 1531–1543 (2013)Cite this article

Abstract

The objective of the current study was to investigate the effect of vanadium (V5+) on Cyp1 expression and activity in C57BL/6 mice liver and isolated hepatocytes. For this purpose, C57BL6 mice were injected intraperitoneally with V5+ (5 mg/kg) in the absence and presence of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) (15 μg/kg) for 6 and 24 h. Furthermore, isolated hepatocytes from C57BL6 mice were treated with V5+ (5, 10, and 20 μM) in the absence and presence of TCDD (1 nM) for 3, 6, 12, and 24 h. In vivo, V5+ alone did not significantly alter Cyp1a1, Cyp1a2, or Cyp1b1 mRNA, protein, or catalytic activity levels. Upon co-exposure to V5+ and TCDD, V5+ significantly potentiated the TCDD-mediated induction of the Cyp1a1, Cyp1a2, and Cyp1b1 mRNA, protein, and catalytic activity levels at 24 h. In vitro, V5+ decreased the TCDD-mediated induction of Cyp1a1 mRNA, protein, and catalytic activity levels. Furthermore, V5+ significantly inhibited the TCDD-induced AhR-dependent luciferase activity. V5+ also increased serum hemoglobin (Hb) levels in animals treated for 24 h. Upon treatment of isolated hepatocytes with Hb alone or in the presence of TCDD, there was an increase in the AhR-dependent luciferase activity. When isolated hepatocytes were treated for 2 h with V5+ in the presence of TCDD, followed by replacement of the medium with new medium containing Hb, there was further potentiation to the TCDD-mediated effect. The present study demonstrates that there is a differential modulation of Cyp1a1 by V5+ in C57BL/6 mice livers and isolated hepatocytes and demonstrates Hb as an in vivo specific modulator.

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Abbreviations

AhR:

Aryl hydrocarbon receptor

V5+ :

Vanadium

Cyp450s:

Cytochrome P450s

HO-1:

Heme oxygenase-1

TCDD:

2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)

XRE:

Xenobiotic responsive element

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Acknowledgments

This work was supported by Natural Sciences and Engineering Research Council of Canada (NSERC) Discovery Grant RGPIN 250139-07 to A.O.S. I.E.A is the recipient of Libyan Government Scholarship. A.A-M. is the recipient of Alberta Ingenuity Graduate Scholarship and Izaak Walton Killam memorial graduate Scholarship.

Conflict of interest

The authors declare no conflict of interest.

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Affiliations

  1. Faculty of Pharmacy and Pharmaceutical Sciences, 2142J Katz Group-Rexall Centre for Pharmacy and Health Research, University of Alberta, Edmonton, AB, T6G 2E1, Canada

    Ghada Abdelhamid, Issa E. A. Amara, Anwar Anwar-Mohamed & Ayman O. S. El-Kadi

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  1. Ghada Abdelhamid
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  2. Issa E. A. Amara
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  3. Anwar Anwar-Mohamed
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  4. Ayman O. S. El-Kadi
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Correspondence to Ayman O. S. El-Kadi.

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Abdelhamid, G., Amara, I.E.A., Anwar-Mohamed, A. et al. Modulation of cytochrome P450 1 (Cyp1) by vanadium in hepatic tissue and isolated hepatocyte of C57BL/6 mice. Arch Toxicol 87, 1531–1543 (2013). https://doi.org/10.1007/s00204-013-1023-7

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Keywords

  • Aryl hydrocarbon receptor
  • C57BL/6 mouse
  • Vanadium
  • Carcinogenesis