The synthetic triterpenoid RTA dh404 (CDDO-dhTFEA) restores Nrf2 activity and attenuates oxidative stress, inflammation, and fibrosis in rats with chronic kidney disease

References

• Aleksunes LM, Goedken MJ, Rockwell CE, et al. (2010). Transcriptional regulation of renal cytoprotective genes by Nrf2 and its potential use as a therapeutic target to mitigate cisplatin-induced nephrotoxicity. J Pharmacol Exp Ther 335:2–12
   PubMed Web of Science ®Google Scholar
• Aminzadeh MA, Nicholas SB, Norris KC, et al. (2013). Role of impaired Nrf2 activation in the pathogenesis of oxidative stress and inflammation in chronic tubulo-interstitial nephropathy. Nephrol Dial Transplant 28:2038–45
   PubMed Web of Science ®Google Scholar
• Chin M, Lee CY, Chuang JC, et al. (2013). Bardoxolone methyl analogs RTA 405 and dh404 are well tolerated and exhibit efficacy in rodent models of Type 2 diabetes and obesity. Am J Physiol Renal Physiol 304:F1438–46
   PubMed Web of Science ®Google Scholar
• de Zeeuw D, Akizawa T, Agarwal R, et al. (2013). Rationale and trial design of bardoxolone methyl evaluation in patients with chronic kidney disease and type 2 diabetes: the occurrence of renal events (BEACON). Am J Nephrol 37:212–22
   PubMed Web of Science ®Google Scholar
• Dinkova-Kostova AT, Liby KT, Stephenson KK, et al. (2005). Extremely potent triterpenoid inducers of the phase 2 response: correlations of protection against oxidant and inflammatory stress. Proc Natl Acad Sci USA 102:4584–9
   PubMed Web of Science ®Google Scholar
• Fujihara CK, Antunes GR, Mattar AL, et al. (2007). Chronic inhibition of nuclear factor-kappaB attenuates renal injury in the 5/6 renal ablation model. Am J Physiol Renal Physiol 292:F92–9
   PubMed Web of Science ®Google Scholar
• Ghosh SS, Massey HD, Krieg R, et al. (2009). Curcumin ameliorates renal failure in 5/6 nephrectomized rats: role of inflammation. Am J Physiol Renal Physiol 296:F1146–57
   PubMed Web of Science ®Google Scholar
• Hong DS, Kurzrock R, Supko JG, et al. (2012). A phase I first-in-human trial of bardoxolone methyl in patients with advanced solid tumors and lymphomas. Clin Cancer Res 18:3396–406
   PubMed Web of Science ®Google Scholar
• Ichikawa T, Li J, Meyer CJ, et al. (2009). Dihydro-CDDO-trifluoroethyl amide (dh404), a novel Nrf2 activator, suppresses oxidative stress in cardiomyocytes. PLoS ONE 4:e8391
   Web of Science ®Google Scholar
• Kim HJ, Vaziri ND. (2010). Contribution of impaired Nrf2-Keap1 pathway to oxidative stress and inflammation in chronic renal failure. Am J Physiol Renal Physiol 298:F662–71
   PubMed Web of Science ®Google Scholar
• Kim HJ, Sato T, Rodriguez-Iturbe B, et al. (2011). Role of intrarenal angiotensin system activation, oxidative stress, inflammation, and impaired nuclear factor-erythroid-2-related factor 2 activity in the progression of focal glomerulosclerosis. J Pharmacol Exp Ther 337:583–90
   PubMed Web of Science ®Google Scholar
• Lee BH, Hsu WH, Chang YY, et al. (2012). Ankaflavin: a natural novel PPARgamma agonist upregulates Nrf2 to attenuate methylglyoxal-induced diabetes in vivo. Free Radic Biol Med 53:2008–16
   PubMed Web of Science ®Google Scholar
• Liby KT, Sporn MB. (2012). Synthetic oleanane triterpenoids: multifunctional drugs with a broad range of applications for prevention and treatment of chronic disease. Pharmacol Rev 64:972–1003
   PubMed Web of Science ®Google Scholar
• Liby KT, Yore MM, Sporn MB. (2007). Triterpenoids and rexinoids as multifunctional agents for the prevention and treatment of cancer. Nat Rev Cancer 7:357–69
   PubMed Web of Science ®Google Scholar
• Li H, Zhang L, Wang F, et al. (2011). Attenuation of glomerular injury in diabetic mice with tert-butylhydroquinone through nuclear factor erythroid 2-related factor 2-dependent antioxidant gene activation. Am J Nephrol 33:289–97
   PubMed Web of Science ®Google Scholar
• Li W, Khor TO, Xu C, et al. (2008). Activation of Nrf2-antioxidant signaling attenuates NFkappaB-inflammatory response and elicits apoptosis. Biochem Pharmacol 76:1485–9
   PubMed Web of Science ®Google Scholar
• Manning RD Jr, Tian N, Meng S. (2005). Oxidative stress and antioxidant treatment in hypertension and the associated renal damage. Am J Nephrol 25:311–17
   PubMed Web of Science ®Google Scholar
• Naito C, Yamanaka T. (1978). Lipid peroxides in atherosclerotic diseases (author’s transl). Nihon Ronen Igakkai Zasshi 15:187–91
   PubMedGoogle Scholar
• Palsamy P, Subramanian S. (2011). Resveratrol protects diabetic kidney by attenuating hyperglycemia-mediated oxidative stress and renal inflammatory cytokines via Nrf2-Keap1 signaling. Biochim Biophys Acta 1812:719–31
   PubMed Web of Science ®Google Scholar
• Peng A, Ye T, Rakheja D, et al. (2011). The green tea polyphenol (−)-epigallocatechin-3-gallate ameliorates experimental immune-mediated glomerulonephritis. Kidney Int 80:601–11
   PubMed Web of Science ®Google Scholar
• Pergola PE, Raskin P, Toto RD, et al. (2011). Bardoxolone methyl and kidney function in CKD with type 2 diabetes. N Engl J Med 365:327–36
   PubMed Web of Science ®Google Scholar
• Quiroz Y, Ferrebuz A, Romero F, et al. (2008). Melatonin ameliorates oxidative stress, inflammation, proteinuria, and progression of renal damage in rats with renal mass reduction. Am J Physiol Renal Physiol 294:F336–44
   PubMed Web of Science ®Google Scholar
• Reisman SA, Chertow GM, Hebbar S, et al. (2012). Bardoxolone methyl decreases megalin and activates nrf2 in the kidney. J Am Soc Nephrol 23:1663–73
   PubMed Web of Science ®Google Scholar
• Reisman SA, Ward KW, Klaassen CD, et al. (2013). CDDO-9,11-dihydro-trifluoroethyl amide (CDDO-dhTFEA) induces hepatic cytoprotective genes and increases bile flow in rats. Xenobiotica 43:571–8
   PubMed Web of Science ®Google Scholar
• Reisman SA, Yeager RL, Yamamoto M, et al. (2009). Increased Nrf2 activation in livers from Keap1-knockdown mice increases expression of cytoprotective genes that detoxify electrophiles more than those that detoxify reactive oxygen species. Toxicol Sci 108:35–47
   PubMed Web of Science ®Google Scholar
• Remuzzi G, Benigni A, Remuzzi A. (2006). Mechanisms of progression and regression of renal lesions of chronic nephropathies and diabetes. J Clin Invest 116:288–96
   PubMed Web of Science ®Google Scholar
• Ruiz S, Pergola PE, Zager RA, et al. (2013). Targeting the transcription factor Nrf2 to ameliorate oxidative stress and inflammation in chronic kidney disease. Kidney Int 83:1029–41
   PubMed Web of Science ®Google Scholar
• Soetikno V, Sari FR, Lakshmanan AP, et al. (2013). Curcumin alleviates oxidative stress, inflammation, and renal fibrosis in remnant kidney through the Nrf2-keap1 pathway. Mol Nutr Food Res 57:1649–59
   PubMed Web of Science ®Google Scholar
• Sporn MB, Liby KT, Yore MM, et al. (2011). New synthetic triterpenoids: potent agents for prevention and treatment of tissue injury caused by inflammatory and oxidative stress. J Nat Prod 74:537–45
   PubMed Web of Science ®Google Scholar
• Tapia E, Soto V, Ortiz-Vega KM, et al. (2012). Curcumin induces Nrf2 nuclear translocation and prevents glomerular hypertension, hyperfiltration, oxidant stress, and the decrease in antioxidant enzymes in 5/6 nephrectomized rats. Oxid Med Cell Longev 2012:269039
   PubMed Web of Science ®Google Scholar
• Tsai PY, Ka SM, Chao TK, et al. (2011). Antroquinonol reduces oxidative stress by enhancing the Nrf2 signaling pathway and inhibits inflammation and sclerosis in focal segmental glomerulosclerosis mice. Free Radic Biol Med 50:1503–16
   PubMed Web of Science ®Google Scholar
• Vaziri ND, Bai Y, Ni Z, et al. (2007). Intra-renal angiotensin II/AT1 receptor, oxidative stress, inflammation, and progressive injury in renal mass reduction. J Pharmacol Exp Ther 323:85–93
   PubMed Web of Science ®Google Scholar
• Vaziri ND, Ni Z, Oveisi F, et al. (2002). Enhanced nitric oxide inactivation and protein nitration by reactive oxygen species in renal insufficiency. Hypertension 39:135–41
   PubMed Web of Science ®Google Scholar
• Vaziri ND, Oveisi F, Ding Y. (1998). Role of increased oxygen free radical activity in the pathogenesis of uremic hypertension. Kidney Int 53:1748–54
   PubMed Web of Science ®Google Scholar
• Wakabayashi N, Slocum SL, Skoko JJ, et al. (2010). When NRF2 talks, who’s listening? Antioxid Redox Signal 13:1649–63
   PubMed Web of Science ®Google Scholar
• Wu QQ, Wang Y, Senitko M, et al. (2011). Bardoxolone methyl (BARD) ameliorates ischemic AKI and increases expression of protective genes Nrf2, PPARgamma, and HO-1. Am J Physiol Renal Physiol 300:F1180–92
   PubMed Web of Science ®Google Scholar
• Xing Y, Niu T, Wang W, et al. (2012). Triterpenoid dihydro-CDDO-trifluoroethyl amide protects against maladaptive cardiac remodeling and dysfunction in mice: a critical role of Nrf2. PLoS ONE 7:e44899
   Web of Science ®Google Scholar
• Yates MS, Tauchi M, Katsuoka F, et al. (2007). Pharmacodynamic characterization of chemopreventive triterpenoids as exceptionally potent inducers of Nrf2-regulated genes. Mol Cancer Ther 6:154–62
   PubMed Web of Science ®Google Scholar
• Yoh K, Hirayama A, Ishizaki K, et al. (2008). Hyperglycemia induces oxidative and nitrosative stress and increases renal functional impairment in Nrf2-deficient mice. Genes Cells 13:1159–70
   PubMed Web of Science ®Google Scholar
• Yoh K, Itoh K, Enomoto A, et al. (2001). Nrf2-deficient female mice develop lupus-like autoimmune nephritis. Kidney Int 60:1343–53
   PubMed Web of Science ®Google Scholar
• Zoja C, Corna D, Nava V, et al. (2013). Analogs of bardoxolone methyl worsen diabetic nephropathy in rats with additional adverse effects. Am J Physiol Renal Physiol 304:F808–19
   PubMed Web of Science ®Google Scholar