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Inhibitory Effect of Gallic Acid on Advanced Glycation End Products Induced Up-Regulation of Inflammatory Cytokines and Matrix Proteins in H9C2 (2-1) Cells

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Abstract

Accumulating evidences have demonstrated that increased production of advanced glycation end products (AGEs) contributes to etiology of cardiac complications in diabetes. However, the underlying mechanism of AGE-induced effects is not well understood. Recent studies evince the beneficial role of phytochemicals in reducing the risk of cardiovascular morbidity and mortality in patients with cardiovascular diseases and diabetes mellitus. Hence, in the present study, the cardio protective role of gallic acid (GA) against in vitro synthesized AGE in H9C2 (2-1) cells was elucidated. H9C2 (2-1) cells exposed to AGE (100 μg/ml) with/without GA pre-treatment (10 μM) and the release of reactive oxygen species (ROS), expression of oxidative stress markers, matrix proteins, and cytokines were analyzed. Cells exposed to AGE demonstrate a significant increase in ROS release with augmented expression (P < 0.01) of receptor for AGE (RAGE) and NOX-p47 phox (P < 0.001) proteins compared to untreated control cells. Moreover, an increased expression of matrix proteins and cytokines such as TNF-α (P < 0.01), TGF-β (P < 0.001), and iNOS (P < 0.001) was also found in AGE-treated cells, whereas, cells pre-treated with N-acetyl cysteine or RAGE neutralizing antibody notably (P < 0.01) impede the ROS release. Further, cells pre-treated with GA significantly attenuated the expression of NOX, RAGE, and other cytokines. In addition, the abnormal expressions of matrix proteins were also decreased especially in GA-treated cells. Thus, the results of the present study demonstrated the deleterious effect of AGEs that directly induce oxidative stress and matrix derangement and, on the other way, the “pleiotropic” activity of GA in reducing the risk of AGE-mediated cellular complications.

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Acknowledgments

This work was supported by JNMF and CSIR, New Delhi, India.

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  1. Department of Biochemistry, University of Madras, Guindy Campus, Chennai, 600 025, Tamil Nadu, India

    Subramanian Umadevi, Venkatachalam Gopi & Elangovan Vellaichamy

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  1. Subramanian Umadevi
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Correspondence to Elangovan Vellaichamy.

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Umadevi, S., Gopi, V. & Vellaichamy, E. Inhibitory Effect of Gallic Acid on Advanced Glycation End Products Induced Up-Regulation of Inflammatory Cytokines and Matrix Proteins in H9C2 (2-1) Cells. Cardiovasc Toxicol 13, 396–405 (2013). https://doi.org/10.1007/s12012-013-9222-2

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