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Role of cytosolic liver fatty acid binding protein in hepatocellular oxidative stress: effect of dexamethasone and clofibrate treatment

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Abstract

The presence of cysteine and methionine groups together with an ability to bind long-chain fatty acid (LCFA) oxidation products makes liver fatty acid binding protein (L-FABP) an attractive candidate against hepatocellular oxidative stress. In this report, we show that pharmacological treatment directed at modulating L-FABP level affected hepatocellular oxidant status. L-FABP expressing 1548-hepatoma cells, treated with dexamethasone or clofibrate, decreased and increased intracellular L-FABP levels, respectively. Oxidative stress was induced by H2O2 incubation or hypoxia–reoxygenation. The fluorescent marker, dichlorofluorescein (DCF), was employed to measure intracellular reactive oxygen species (ROS). Hepatocellular damage was assessed by lactate dehydrogenase (LDH) level. Dexamethasone treatment resulted in a significant increase in DCF fluorescence with higher LDH release compared to control cells. Clofibrate treatment, however, resulted in a significant decrease in both parameters (p < 0.05). Drug treatments did not affect cytosolic activites of glutathione peroxidase (GPx), superoxide dismutase (SOD), or catalase suggesting that the differences between treated and control cells may likely be associated with varying L-FABP levels. We conclude that L-FABP may act as an effective endogenous cytoprotectant against hepatocellular oxidative stress.

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Acknowledgments

This work was supported by an operating grant from the Canadian Institute of Health Research. G. Rajaraman gratefully acknowledges support of a University of Manitoba Fellowship Award and the Leslie Buggey Scholarship.

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Authors and Affiliations

  1. Faculty of Pharmacy, University of Manitoba, 50 Sifton Road, R3T 2N2, Winnipeg, Manitoba, Canada

    G. Rajaraman, G. Q. Wang, J. Yan, P. Jiang, Y. Gong & F. J. Burczynski

  2. Department of Pharmacology, Faculty of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada

    F. J. Burczynski

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  1. G. Rajaraman
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  2. G. Q. Wang
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  3. J. Yan
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  4. P. Jiang
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  6. F. J. Burczynski
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Correspondence to F. J. Burczynski.

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Rajaraman, G., Wang, G.Q., Yan, J. et al. Role of cytosolic liver fatty acid binding protein in hepatocellular oxidative stress: effect of dexamethasone and clofibrate treatment. Mol Cell Biochem 295, 27–34 (2007). https://doi.org/10.1007/s11010-006-9268-6

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  • DOI: https://doi.org/10.1007/s11010-006-9268-6

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