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Experimental evidence for the therapeutic potential of tempol in the treatment of acute liver injury

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Abstract

Oxidative stress is one of the mechanisms involved in the acute carbon tetrachloride (CCl4)-induced hepatotoxicity. Since 4-hydroxy-2,2,6,6-tetramethylpiperidin-1-oxyl, known as tempol, has powerful antioxidant properties, we investigated its potential hepatoprotective effects and the underlying mechanisms that may add further benefits for its clinical usefulness using an acute model of CCl4-induced hepatotoxicity. One hour after CCl4 induction of acute hepatotoxicity, mice were treated with a daily dose of 20 mg/kg/day tempol for 3 days. It was found that treatment of animals with tempol significantly negated the pathological changes in liver function parameters as well as histology induced by CCl4. In addition, tempol significantly ameliorated CCl4-induced lipid peroxidation and GSH depletion, and improved catalase activity. Furthermore, tempol alleviated the inflammation induced by CCl4 as indicated by reducing the liver expression level of nuclear factor-kappa B (NF-κB) and tumor necrosis factor-α (TNF-α). Finally, tempol significantly reduced expression level of the B-cell lymphoma-2 protein (Bcl-2) and active caspase-3 which are known markers of apoptosis. In conclusion, the present study provides important evidences for the promising hepatoprotective effects of tempol that can be explained by amelioration of oxidative stress mainly through replenishment of GSH, restoration of antioxidant enzyme activities, and reduction of lipid peroxides alongside its anti-inflammatory properties.

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Acknowledgments

Dr. Mariana Fathy Kamel, lecturer of pathology at Faculty of Medicine, Minia University for her useful comments, remarks, and great effort in analyzing the histopathological findings.

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Authors and Affiliations

  1. Departments of Pharmacology and Toxicology, College of Pharmacy, Taibah University, Medina, Kingdom of Saudi Arabia

    Mekky M. Abouzied & Heba M. Eltahir

  2. Department of Biochemistry, Faculty of Pharmacy, Minia University, Minia, Egypt

    Mekky M. Abouzied

  3. Department of Pharmacology & Toxicology, Faculty of Pharmacy, Minia University, Minia, Egypt

    Ashraf Taye

  4. Department of Pharmacology & Toxicology, Faculty of Medicine, Assiut University, Assiut, Egypt

    Mahran S. Abdelrahman

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  1. Mekky M. Abouzied
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  2. Heba M. Eltahir
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Correspondence to Mekky M. Abouzied.

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Abouzied, M.M., Eltahir, H.M., Taye, A. et al. Experimental evidence for the therapeutic potential of tempol in the treatment of acute liver injury. Mol Cell Biochem 411, 107–115 (2016). https://doi.org/10.1007/s11010-015-2572-2

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