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Inhibition of TNF-α protects against hepatic ischemia–reperfusion injury in rats via NF-κB dependent pathway

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Abstract

Hepatic ischemia–reperfusion injury (I/R) is a serious health problem associated with liver transplantation, resection surgery, and various types of shock especially hemorrhagic shock. In the present investigation, the effect of inhibition of tumor necrosis factor-alpha (TNF-α) using pentoxifylline or infliximab against hepatic I/R injury induced in rats by 45-min ischemia and 1-h reperfusion was studied. It was observed that both pentoxifylline and infliximab-treated groups showed a significantly lower extent and severity of liver injury. This is attributed to (1) a decrease in oxidative stress markers, (2) reduction of the expression of TNF-α, TNF-α type-1 receptors, and nuclear factor kappa B (NF-κB). Thus TNF-α inhibition may be one of the therapeutic interventions to overcome the deleterious effects of I/R on liver via reduction of oxidative stress and inhibition of inflammatory cascade.

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Acknowledgments

The authors would like to thank Professor Laila Rashed (Biochemistry Department, Faculty of Medicine, Cairo University, Egypt) for assistance in performing PCR technique.

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The authors declare no conflict of interest.

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Authors and Affiliations

  1. Department of Pharmacology and Toxicology, Faculty of Pharmacy, Zagazig University, Zagazig, 44519, Egypt

    Mona F. Mahmoud, Shimaa M. El Shazly & Waleed Barakat

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  1. Mona F. Mahmoud
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  2. Shimaa M. El Shazly
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  3. Waleed Barakat
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Correspondence to Mona F. Mahmoud.

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Mahmoud, M.F., El Shazly, S.M. & Barakat, W. Inhibition of TNF-α protects against hepatic ischemia–reperfusion injury in rats via NF-κB dependent pathway. Naunyn-Schmiedeberg's Arch Pharmacol 385, 465–471 (2012). https://doi.org/10.1007/s00210-012-0729-z

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  • DOI: https://doi.org/10.1007/s00210-012-0729-z

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