Oxidative Medicine and Cellular Longevity

Oxidative Stress in Metabolic Disorders and Drug-Induced Injury: The Potential Role of Nrf2 and PPARs Activators


Status
Published

1Beni-Suef University, Beni-Suef, Egypt

2Manchester Metropolitan University, Manchester, UK

3Cumhuriyet University, Sivas, Turkey

4Sapienza University of Rome, Rome, Italy


Oxidative Stress in Metabolic Disorders and Drug-Induced Injury: The Potential Role of Nrf2 and PPARs Activators

Description

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. 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, and glutathione peroxidase glutathione-s-transferase. Thus, Nrf2 plays a role as 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.

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 (PPARα, PPARβ/δ, and PPARγ) belong to a superfamily of nuclear receptors that function as transcription factors regulating the expression of multiple genes. Upon ligand binding, they form heterodimers with retinoid X receptor (RXR) and result in modulation of gene transcription. PPARs regulate a variety of biological processes in various tissues. Among their effects, PPARα controls lipid metabolism and inflammatory processes, PPARβ/δ regulates glucose utilization, cell differentiation, and inflammation, and PPARγ is involved in adipocyte differentiation, glucose metabolism, and inflammatory pathways. Upon activation, PPARs are known to exert anti-inflammatory and antioxidant properties via suppressing nuclear factor-κB, decreasing ROS production, and upregulating the expression of antioxidant enzymes.

Recent reports point to coactivation and possible interaction between PPARs and Nrf2 through multiple mechanisms. Ongoing and future research will probably provide efficient PPARs and Nrf2 modulating agents for preventing and treating metabolic and other common disorders. Our aim is to bring together novel research and insight views on the role of Nrf2 and PPARs in modulating oxidative stress and inflammation. We invite investigators to contribute original research as well as review articles that illustrate the usefulness of PPARs and Nrf2 as novel therapeutic targets for both metabolic and drug-induced disorders.

Potential topics include but are not limited to the following:

  • Pharmacological targeting of PPARs and Nrf2 in the context of disease
  • PPARs and Nrf2 ligands as therapeutic agents in metabolic and drug-induced disorders
  • Role of PPARs and Nrf2 in different diseases
  • Crosstalk between PPARs and Nrf2 signaling pathways
  • Molecular mechanisms of synthetic and natural agents targeting Nrf2 and/or PPARs isoforms
  • Possible interaction mechanisms between Nrf2 and PPARs
  • Role of oxidative stress and inflammation in metabolic and drug-induced disorders
  • Mechanisms of drug-induced organ damage
  • Regulatory mechanisms within the Nrf2 and PPARs pathways
  • Possible toxicity associated with the exposure to PPAR or Nrf2 ligands

Articles

  • Special Issue
  • - Volume 2017
  • - Article ID 2508909
  • - Editorial

Oxidative Stress in Metabolic Disorders and Drug-Induced Injury: The Potential Role of Nrf2 and PPARs Activators

Ayman M. Mahmoud | M. Yvonne Alexander | ... | Alessandro Venditti
  • Special Issue
  • - Volume 2017
  • - Article ID 1284804
  • - Research Article

Probucol Protects Rats from Cardiac Dysfunction Induced by Oxidative Stress following Cardiopulmonary Resuscitation

Xu Xiao | Huiyuan Hou | ... | Peter X. Shaw
  • Special Issue
  • - Volume 2017
  • - Article ID 9237263
  • - Review Article

The Role of Nrf2 in Cardiovascular Function and Disease

Sandro Satta | Ayman M. Mahmoud | ... | Stephen J. White
  • Special Issue
  • - Volume 2017
  • - Article ID 1378175
  • - Review Article

Collaborative Power of Nrf2 and PPARγ Activators against Metabolic and Drug-Induced Oxidative Injury

Choongho Lee
  • Special Issue
  • - Volume 2017
  • - Article ID 8254289
  • - Review Article

Modulatory Mechanism of Polyphenols and Nrf2 Signaling Pathway in LPS Challenged Pregnancy Disorders

Tarique Hussain | Bie Tan | ... | Yulong Yin
  • Special Issue
  • - Volume 2017
  • - Article ID 9091879
  • - Research Article

Expression of the NRF2 Target Gene NQO1 Is Enhanced in Mononuclear Cells in Human Chronic Kidney Disease

Jianlin Shen | Marianne Rasmussen | ... | Alexandra Scholze
  • Special Issue
  • - Volume 2017
  • - Article ID 7369671
  • - Research Article

Commiphora molmol Modulates Glutamate-Nitric Oxide-cGMP and Nrf2/ARE/HO-1 Pathways and Attenuates Oxidative Stress and Hematological Alterations in Hyperammonemic Rats

Ayman M. Mahmoud | Sultan Alqahtani | ... | Ahmed A. Allam
  • Special Issue
  • - Volume 2017
  • - Article ID 3172692
  • - Research Article

NRF2 Plays a Critical Role in Both Self and EGCG Protection against Diabetic Testicular Damage

Chenyu Pan | Shengzhu Zhou | ... | Hao Wu
  • Special Issue
  • - Volume 2017
  • - Article ID 3420286
  • - Research Article

Genetic Nrf2 Overactivation Inhibits the Deleterious Effects Induced by Hepatocyte-Specific c-met Deletion during the Progression of NASH

Pierluigi Ramadori | Hannah Drescher | ... | Daniela C. Kroy
  • Special Issue
  • - Volume 2017
  • - Article ID 4156361
  • - Research Article

Antioxidant Treatment Induces Hyperactivation of the HPA Axis by Upregulating ACTH Receptor in the Adrenal and Downregulating Glucocorticoid Receptors in the Pituitary

Jessika P. Prevatto | Rafael C. Torres | ... | Vinicius F. Carvalho
Oxidative Medicine and Cellular Longevity
 Journal metrics
Acceptance rate48%
Submission to final decision56 days
Acceptance to publication37 days
CiteScore7.300
Impact Factor5.076
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