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Ayman M. Mahmoud [1] and M. Yvonne Alexander [2] and Yusuf Tutar [3] and Fiona L. Wilkinson [2] and Alessandro Venditti [4]
1, Physiology Division, Department of Zoology, Faculty of Science, Beni Suef University, Beni Suef, Egypt, bsu.edu.eg
2, Vascular Pathology Group, Centre for Biomedicine, School of Healthcare Science, Manchester Metropolitan University, Manchester, UK, mmu.ac.uk
3, University of Health Sciences, Mekteb-i Tıbbiye-i Şahane, Istanbul, Turkey, sbu.edu.tr
4, Department of Chemistry, Sapienza University of Rome, Rome, Italy, uniroma1.it
Received Oct 25, 2017; Accepted Oct 26, 2017
This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Oxidative stress plays a major role in metabolic disorders and a wide range of chronic diseases such as diabetes mellitus, obesity, metabolic syndrome, aging, cancer, osteoporosis, rheumatoid arthritis, cardiovascular diseases, and neurodegenerative disorders. In addition, drug-induced organ injury is well known to be associated with oxidative stress and inflammation. Considerable evidence indicates that oxidative stress and inflammation are the key pathophysiological processes underpinning these disorders. Therefore, modulation of oxidative stress represents an important strategy for the treatment of multiple human diseases.
The transcription factor nuclear factor erythroid 2 related factor 2 (Nrf2) is the master regulator of the basal and inducible expression of a large network of cytoprotective and antioxidant genes [1]. Under basal conditions, Nrf2 is bound to Kelch-like ECH-associated protein 1 (Keap1) which functions as a sensor protein against electrophiles and reactive oxygen species (ROS). Upon cell stimulation, Nrf2 dissociates from Keap1 and activated Nrf2 is translocated into the nucleus where it binds to the antioxidant response element (ARE) and leads to expression of target genes including heme oxygenase-1, NAD(P)H:quinone oxidoreductase 1, superoxide dismutase, catalase, glutathione peroxidase, and glutathione-S-transferase [2]. Thus, Nrf2 plays a role as a multiorgan protector against oxidative stress via inducing target genes. In recent years, Nrf2 has shown promise as a novel therapeutic target in diseases with underlying oxidative and inflammatory stress components [3–6].
Peroxisome proliferator-activated receptors (PPARs) are proteins that belong to the nuclear receptor family of ligand-activated transcription factors. The three main forms of peroxisome proliferator-activated receptors (PPAR