title: Effect of redox modulating NRF2 activators on chronic kidney disease.
abstract: Chronic kidney disease (CKD) is featured by a progressive decline of kidney function and is mainly caused by chronic diseases such as diabetes mellitus and hypertension. CKD is a complex disease due to cardiovascular complications and high morbidity; however, there is no single treatment to improve kidney function in CKD patients. Since biological markers representing oxidative stress are significantly elevated in CKD patients, oxidative stress is receiving attention as a contributing factor to CKD pathology. Nuclear factor erythroid-2 related factor 2 (NRF2) is a predominant transcription factor that regulates the expression of a wide array of genes encoding antioxidant proteins, thiol molecules and their generating enzymes, detoxifying enzymes, and stress response proteins, all of which can counteract inflammatory and oxidative damages. There is considerable experimental evidence suggesting that NRF2 signaling plays a protective role in renal injuries that are caused by various pathologic conditions. In addition, impaired NRF2 activity and consequent target gene repression have been observed in CKD animals. Therefore, a pharmacological intervention activating NRF2 signaling can be beneficial in protecting against kidney dysfunction in CKD. This review article provides an overview of the role of NRF2 in experimental CKD models and describes current findings on the renoprotective effects of naturally occurring NRF2 activators, including sulforaphane, resveratrol, curcumin, and cinnamic aldehyde. These experimental results, coupled with recent clinical experiences with a synthetic triterpenoid, bardoxolone methyl, have brought a light of hope for ameliorating CKD progression by preventing oxidative stress and maintaining cellular redox homeostasis.
authors.affiliation: College of Pharmacy, The Catholic University of Korea, Bucheon, Gyeonggi-do 420-743, Korea. bhchoi37@gmail.com.
authors.forename: Bo-hyun
authors.initials: BH
authors.lastname: Choi
authors.affiliation: Daewon Foreign Language High School, Kwangjin-gu, Seoul 143-713, Korea. ks960127@naver.com.
authors.forename: Kyung-Shin
authors.initials: KS
authors.lastname: Kang
authors.affiliation: College of Pharmacy, The Catholic University of Korea, Bucheon, Gyeonggi-do 420-743, Korea. mkwak@catholic.ac.kr.
authors.forename: Mi-Kyoung
authors.initials: MK
authors.lastname: Kwak
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D008297:Male; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000378:metabolism*; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000235:genetics; D051436:Renal Insufficiency, Chronic / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics
chemical_list: D000975:Antioxidants; D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human