Could physical exercises modulate Nrf2–Keap1 pathway in chronic kidney disease?

Abstract

Patients with chronic kidney disease (CKD) have various metabolic disorders caused by a chronic state of oxidative stress and inflammation, and recently, nuclear factor-erythroid 2-related factor 2 (Nrf2) has emerged as a factor that plays a significant role in cellular protection against oxidative stress and inflammation. This transcription factor when activated can regulate antioxidant and anti-inflammatory cellular responses leading to the expression of detoxifying enzymes. Studies have shown that Nrf2 expression can be modulated by several factors, such as bioactive compounds and physical exercise. In fact, exercise in CKD patients can bring many benefits; however, there are no studies correlating physical activity and Nrf2 expression in CKD patients. This review aims to discuss whether there is any evidence to justify a recommendation of physical exercise in CKD patients as a non-pharmacological option to activate the Nrf2 pathway.

Astaxanthin Attenuates Adriamycin-Induced Focal Segmental Glomerulosclerosis

“…Using CKD animal models, plenty of data suggests that natural Nrf2 activators exert protective effects by ameliorating the production of ROS and increasing the antioxidant capacity [19]. As CKD-associated oxidative stress is partly due to a diminished antioxidant capacity which is largely caused by impaired activation of Nrf2, interventions aimed at restoring Nrf2 may be effective in retarding CKD progression [20].…”

Could Low-Protein Diet Modulate Nrf2 Pathway in Chronic Kidney Disease?

“…Bioactive foods containing substances such as polyphenols, catechins, resveratrol, sulforaphane, allicin, curcumin, and lycopene, as well as physical exercise all seem have an important role in Nrf2 activation. 5,10,15,[53][54][55][56][57][58] In addition to numerous other benefits of reducing dietary protein intake in the predialysis stages of CKD, there are reasons to hypothesize that LPD modulates the expression of NF-kB and consecutively the expression of Nrf2.…”

“…Then, the increased risk of heart failure with the pharmacological Nrf2 agonist bardoxolone methyl showed the renal community that manipulation of Nrf2 requires heightened watchfulness for unexpected side effects. 13 Since nonpharmacological interventions, such as physical exercise 15 and nutritional compounds 5,15,16 modulate Nrf2 expression in CKD, nonpharmacological stimulation of Nrf2 may be a more attractive approach to restore Nrf2 activity. Low-protein diet (LPD) is an important nonpharmacological therapeutic interventions in nondialysis CKD.…”

An Update on the Role of Nrf2 and its Activators in Diseases Associated with Oxidative Stress

“…Oxidative stress (OS) plays a major role in the development and progression of a wide range of diseases including Alzheimer disease, cancer, atherosclerosis [1] , chronic kidney disease [2] , multiple sclerosis, Niemann-Pick C, Parkinson's disease, Friedreich's ataxia, Huntington's disease (HD), infantile neuroaxonal degeneration, neurodegeneration with brain iron accumulation (NBIA) and lipid metabolism deregulation syndrome like Zellweger syndrome [3] . An assumption also exists currently that OS could cause cancer in patients with Type 2 Diabetes Mellitus (T2DM) [4,5] .…”

“…Nrf2 also augments the activity of stress response proteins, such as heme oxygenase-1 (HO-1), which affects a variety of cellular functions and upregulation of metal chelators, metallothionein1/2 (MT1/2) and ferritin. Non-enzymatic antioxidants like NAD(P)H quinone oxoreductase (NQO1), GPx, glutathione S-transferase, and thiols are also upregulated by Nrf2 [2,15,16] . It is clear that Nrf2 plays a role in protecting cells against OS and this property of Nrf2 makes it an interesting target in several diseases where OS plays a significant role in pathogenesis.…”