1. Boudina S, Abel ED. Diabetic cardiomyopathy revisited. Circulation 2007;115:3213-3223.
Article PubMed
2. Monkemann H, De Vriese AS, Blom HJ, Kluijtmans LA, Heil SG, Schild HH, Golubnitschaja O. Early molecular events in the development of the diabetic cardiomyopathy. Amino Acids 2002;23:331-336.
Article PubMed
3. Cai L, Kang YJ. Oxidative stress and diabetic cardiomyopathy: a brief review. Cardiovasc Toxicol 2001;1:181-193.
Article PubMed
4. Hamblin M, Friedman DB, Hill S, Caprioli RM, Smith HM, Hill MF. Alterations in the diabetic myocardial proteome coupled with increased myocardial oxidative stress underlies diabetic cardiomyopathy. J Mol Cell Cardiol 2007;42:884-895.
Article PubMed PMC
5. Cai L, Wang Y, Zhou G, Chen T, Song Y, Li X, Kang YJ. Attenuation by metallothionein of early cardiac cell death via suppression of mitochondrial oxidative stress results in a prevention of diabetic cardiomyopathy. J Am Coll Cardiol 2006;48:1688-1697.
Article PubMed
6. Adeghate E. Molecular and cellular basis of the aetiology and management of diabetic cardiomyopathy: a short review. Mol Cell Biochem 2004;261:187-191.
Article PubMed
7. Doroshow JH, Locker GY, Myers CE. Enzymatic defenses of the mouse heart against reactive oxygen metabolites: alterations produced by doxorubicin. J Clin Invest 1980;65:128-135.
Article PubMed PMC
8. Chen Y, Saari JT, Kang YJ. Weak antioxidant defenses make the heart a target for damage in copper-deficient rats. Free Radic Biol Med 1994;17:529-536.
Article PubMed
9. Di Filippo C, Marfella R, Cuzzocrea S, Piegari E, Petronella P, Giugliano D, Rossi F, D'Amico M. Hyperglycemia in streptozotocin-induced diabetic rat increases infarct size associated with low levels of myocardial HO-1 during ischemia/reperfusion. Diabetes 2005;54:803-810.
Article PubMed
10. Bruce CR, Carey AL, Hawley JA, Febbraio MA. Intramuscular heat shock protein 72 and heme oxygenase-1 mRNA are reduced in patients with type 2 diabetes: evidence that insulin resistance is associated with a disturbed antioxidant defense mechanism. Diabetes 2003;52:2338-2345.
Article PubMed
11. Liu X, Wei J, Peng DH, Layne MD, Yet SF. Absence of heme oxygenase-1 exacerbates myocardial ischemia/reperfusion injury in diabetic mice. Diabetes 2005;54:778-784.
Article PubMed
12. Koh KK, Oh PC, Quon MJ. Does reversal of oxidative stress and inflammation provide vascular protection? Cardiovasc Res 2009;81:649-659.
Article PubMed
13. Giannini C, Lombardo F, Curro F, Pomilio M, Bucciarelli T, Chiarelli F, Mohn A. Effects of high-dose vitamin E supplementation on oxidative stress and microalbuminuria in young adult patients with childhood onset type 1 diabetes mellitus. Diabetes Metab Res Rev 2007;23:539-546.
Article PubMed
14. Ceriello A. New insights on oxidative stress and diabetic complications may lead to a "causal" antioxidant therapy. Diabetes Care 2003;26:1589-1596.
Article PubMed
15. Cai L. Diabetic cardiomyopathy and its prevention by metallothionein: experimental evidence, possible mechanisms and clinical implications. Curr Med Chem 2007;14:2193-2203.
Article PubMed
16. Cai L, Klein JB, Kang YJ. Metallothionein inhibits peroxynitrite-induced DNA and lipoprotein damage. J Biol Chem 2000;275:38957-38960.
Article PubMed
17. Quesada AR, Byrnes RW, Krezoski SO, Petering DH. Direct reaction of H2O2 with sulfhydryl groups in HL-60 cells: zinc-metallothionein and other sites. Arch Biochem Biophys 1996;334:241-250.
Article PubMed
18. Thornalley PJ, Vasak M. Possible role for metallothionein in protection against radiation-induced oxidative stress. Kinetics and mechanism of its reaction with superoxide and hydroxyl radicals. Biochim Biophys Acta 1985;827:36-44.
Article PubMed
19. Cai L, Wang J, Li Y, Sun X, Wang L, Zhou Z, Kang YJ. Inhibition of superoxide generation and associated nitrosative damage is involved in metallothionein prevention of diabetic cardiomyopathy. Diabetes 2005;54:1829-1837.
Article PubMed
20. Zhou G, Li X, Hein DW, Xiang X, Marshall JP, Prabhu SD, Cai L. Metallothionein suppresses angiotensin II-induced nicotinamide adenine dinucleotide phosphate oxidase activation, nitrosative stress, apoptosis, and pathological remodeling in the diabetic heart. J Am Coll Cardiol 2008;52:655-666.
Article PubMed
21. Xu J, Wang G, Wang Y, Liu Q, Xu W, Tan Y, Cai L. Diabetes- and angiotensin II-induced cardiac endoplasmic reticulum stress and cell death: metallothionein protection. J Cell Mol Med 2009;13(8A):1499-1512.
Article PubMed PMC
22. Wang Y, Feng W, Xue W, Tan Y, Hein DW, Li XK, Cai L. Inactivation of GSK-3beta by metallothionein prevents diabetes-related changes in cardiac energy metabolism, inflammation, nitrosative damage, and remodeling. Diabetes 2009;58:1391-1402.
Article PubMed PMC
23. Cai L. Suppression of nitrative damage by metallothionein in diabetic heart contributes to the prevention of cardiomyopathy. Free Radic Biol Med 2006;41:851-861.
Article PubMed
24. Yang L, Li H, Yu T, Zhao H, Cherian MG, Cai L, Liu Y. Polymorphisms in metallothionein-1 and -2 genes associated with the risk of type 2 diabetes mellitus and its complications. Am J Physiol Endocrinol Metab 2008;294:E987-E992.
Article PubMed
25. Li J, Ichikawa T, Janicki JS, Cui T. Targeting the Nrf2 pathway against cardiovascular disease. Expert Opin Ther Targets 2009;13:785-794.
Article PubMed
26. Nguyen T, Nioi P, Pickett CB. The Nrf2-antioxidant response element signaling pathway and its activation by oxidative stress. J Biol Chem 2009;284:13291-13295.
Article PubMed PMC
27. He X, Kan H, Cai L, Ma Q. Nrf2 is critical in defense against high glucose-induced oxidative damage in cardiomyocytes. J Mol Cell Cardiol 2009;46:47-58.
Article PubMed
28. Tan Y, Ichikawa T, Li J, Si Q, Yang H, Chen X, Goldblatt CS, Meyer CJ, Li X, Cai L, Cui T. Diabetic downregulation of Nrf2 activity via ERK contributes to oxidative stress-induced insulin resistance in cardiac cells in vitro and in vivo. Diabetes 2011;60:625-633.
Article PubMed PMC
29. Cheng X, Chapple SJ, Patel B, Puszyk W, Sugden D, Yin X, Mayr M, Siow RC, Mann GE. Gestational diabetes mellitus impairs Nrf2-mediated adaptive antioxidant defenses and redox signaling in fetal endothelial cells in utero. Diabetes 2013;62:4088-4097.
Article PubMed PMC
30. Velmurugan GV, Sundaresan NR, Gupta MP, White C. Defective Nrf2-dependent redox signalling contributes to microvascular dysfunction in type 2 diabetes. Cardiovasc Res 2013;100:143-150.
Article PubMed PMC
31. Yagishita Y, Fukutomi T, Sugawara A, Kawamura H, Takahashi T, Pi J, Uruno A, Yamamoto M. Nrf2 protects pancreatic β-cells from oxidative and nitrosative stress in diabetic model mice. Diabetes 2014;63:605-618.
Article PubMed
32. Uruno A, Furusawa Y, Yagishita Y, Fukutomi T, Muramatsu H, Negishi T, Sugawara A, Kensler TW, Yamamoto M. The Keap1-Nrf2 system prevents onset of diabetes mellitus. Mol Cell Biol 2013;33:2996-3010.
Article PubMed PMC
33. Xu Z, Wei Y, Gong J, Cho H, Park JK, Sung ER, Huang H, Wu L, Eberhart C, Handa JT, Du Y, Kern TS, Thimmulappa R, Barber AJ, Biswal S, Duh EJ. NRF2 plays a protective role in diabetic retinopathy in mice. Diabetologia 2014;57:204-213.
Article PubMed
34. Zhong Q, Mishra M, Kowluru RA. Transcription factor Nrf2-mediated antioxidant defense system in the development of diabetic retinopathy. Invest Ophthalmol Vis Sci 2013;54:3941-3948.
Article PubMed PMC
35. Miao X, Cui W, Sun W, Xin Y, Wang B, Tan Y, Cai L, Miao L, Fu Y, Su G, Wang Y. Therapeutic effect of MG132 on the aortic oxidative damage and inflammatory response in OVE26 type 1 diabetic mice. Oxid Med Cell Longev 2013;2013:879516
Article PubMed PMC
36. Wang Y, Sun W, Du B, Miao X, Bai Y, Xin Y, Tan Y, Cui W, Liu B, Cui T, Epstein PN, Fu Y, Cai L. Therapeutic effect of MG-132 on diabetic cardiomyopathy is associated with its suppression of proteasomal activities: roles of Nrf2 and NF-kappaB. Am J Physiol Heart Circ Physiol 2013;304:H567-H578.
Article PubMed
37. Zheng H, Whitman SA, Wu W, Wondrak GT, Wong PK, Fang D, Zhang DD. Therapeutic potential of Nrf2 activators in streptozotocin-induced diabetic nephropathy. Diabetes 2011;60:3055-3066.
Article PubMed PMC
38. Cui W, Bai Y, Miao X, Luo P, Chen Q, Tan Y, Rane MJ, Miao L, Cai L. Prevention of diabetic nephropathy by sulforaphane: possible role of nrf2 upregulation and activation. Oxid Med Cell Longev 2012;2012:821936
Article PubMed PMC
39. Miao X, Bai Y, Sun W, Cui W, Xin Y, Wang Y, Tan Y, Miao L, Fu Y, Su G, Cai L. Sulforaphane prevention of diabetes-induced aortic damage was associated with the up-regulation of Nrf2 and its downstream antioxidants. Nutr Metab (Lond) 2012;9:84
Article PubMed PMC
40. Cui W, Li B, Bai Y, Miao X, Chen Q, Sun W, Tan Y, Luo P, Zhang C, Zheng S, Epstein PN, Miao L, Cai L. Potential role for Nrf2 activation in the therapeutic effect of MG132 on diabetic nephropathy in OVE26 diabetic mice. Am J Physiol Endocrinol Metab 2013;304:E87-E99.
Article PubMed
41. Miao X, Wang Y, Sun J, Sun W, Tan Y, Cai L, Zheng Y, Su G, Liu Q, Wang Y. Zinc protects against diabetes-induced pathogenic changes in the aorta: roles of metallothionein and nuclear factor (erythroid-derived 2)-like 2. Cardiovasc Diabetol 2013;12:54
Article PubMed PMC
42. Bai Y, Cui W, Xin Y, Miao X, Barati MT, Zhang C, Chen Q, Tan Y, Cui T, Zheng Y, Cai L. Prevention by sulforaphane of diabetic cardiomyopathy is associated with up-regulation of Nrf2 expression and transcription activation. J Mol Cell Cardiol 2013;57:82-95.
Article PubMed
43. Chin M, Lee CY, Chuang JC, Bumeister R, Wigley WC, Sonis ST, Ward KW, Meyer C. 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 2013;304:F1438-F1446.
Article PubMed
44. Wang Y, Zhang Z, Sun W, Tan Y, Liu Y, Zheng Y, Liu Q, Cai L, Sun J. Sulforaphane attenuation of type 2 diabetes-induced aortic damage was associated with the upregulation of Nrf2 expression and function. Oxid Med Cell Longev 2014;2014:123963
Article PubMed PMC
45. Negi G, Kumar A, Sharma SS. Nrf2 and NF-kappaB modulation by sulforaphane counteracts multiple manifestations of diabetic neuropathy in rats and high glucose-induced changes. Curr Neurovasc Res 2011;8:294-304.
Article PubMed
46. Luo ZF, Qi W, Feng B, Mu J, Zeng W, Guo YH, Pang Q, Ye ZL, Liu L, Yuan FH. Prevention of diabetic nephropathy in rats through enhanced renal antioxidative capacity by inhibition of the proteasome. Life Sci 2011;88:512-520.
Article PubMed
47. Shin S, Wakabayashi J, Yates MS, Wakabayashi N, Dolan PM, Aja S, Liby KT, Sporn MB, Yamamoto M, Kensler TW. Role of Nrf2 in prevention of high-fat diet-induced obesity by synthetic triterpenoid CDDO-imidazolide. Eur J Pharmacol 2009;620:138-144.
Article PubMed PMC
48. Tan SM, Sharma A, Stefanovic N, Yuen DY, Karagiannis TC, Meyer C, Ward KW, Cooper ME, de Haan JB. A derivative of Bardoxolone methyl, dh404, in an inverse dose-dependent manner, lessens diabetes-associated atherosclerosis and improves diabetic kidney disease. Diabetes 2014;63:3091-3103.
Article PubMed
49. Liu Y, Wang Y, Miao X, Zhou S, Tan Y, Liang G, Zheng Y, Liu Q, Sun J, Cai L. Inhibition of JNK by compound C66 prevents pathological changes of the aorta in STZ-induced diabetes. J Cell Mol Med 2014;18:1203-1212.
Article PubMed PMC
50. Abo-Salem OM, Harisa GI, Ali TM, El-Sayed ES, Abou-Elnour FM. Curcumin ameliorates streptozotocin-induced heart injury in rats. J Biochem Mol Toxicol 2014;28:263-270.
Article PubMed
51. Wang Y, Zhou S, Sun W, McClung K, Pan Y, Liang Q, Tan Y, Zhao Y, Liu Q, Sun J, Cai L. Inhibition of JNK by novel curcumin analog C66 prevents diabetic cardiomyopathy with a preservation of cardiac metallothionein expression. Am J Physiol Endocrinol Metab 2014;306:E1239-E1247.
Article PubMed
52. Castro CN, Barcala Tabarrozzi AE, Winnewisser J, Gimeno ML, Antunica Noguerol M, Liberman AC, Paz DA, Dewey RA, Perone MJ. Curcumin ameliorates autoimmune diabetes. Evidences in accelerated murine models of type 1 diabetes. Clin Exp Immunol 2014;177:149-160.
Article PubMed PMC
53. Chuengsamarn S, Rattanamongkolgul S, Phonrat B, Tungtrongchitr R, Jirawatnotai S. Reduction of atherogenic risk in patients with type 2 diabetes by curcuminoid extract: a randomized controlled trial. J Nutr Biochem 2014;25:144-150.
Article PubMed
54. Zhao WC, Zhang B, Liao MJ, Zhang WX, He WY, Wang HB, Yang CX. Curcumin ameliorated diabetic neuropathy partially by inhibition of NADPH oxidase mediating oxidative stress in the spinal cord. Neurosci Lett 2014;560:81-85.
Article PubMed
55. Thomas J, Garg ML, Smith DW. Dietary resveratrol supplementation normalizes gene expression in the hippocampus of streptozotocin-induced diabetic C57Bl/6 mice. J Nutr Biochem 2014;25:313-318.
Article PubMed
56. Sadi G, Bozan D, Yildiz HB. Redox regulation of antioxidant enzymes: post-translational modulation of catalase and glutathione peroxidase activity by resveratrol in diabetic rat liver. Mol Cell Biochem 2014;393:111-122.
Article PubMed
57. Guo R, Liu B, Wang K, Zhou S, Li W, Xu Y. Resveratrol ameliorates diabetic vascular inflammation and macrophage infiltration in db/db mice by inhibiting the NF-kappaB pathway. Diab Vasc Dis Res 2014;11:92-102.
Article PubMed
58. Bresciani L, Calani L, Bocchi L, Delucchi F, Savi M, Ray S, Brighenti F, Stilli D, Del Rio D. Bioaccumulation of resveratrol metabolites in myocardial tissue is dose-time dependent and related to cardiac hemodynamics in diabetic rats. Nutr Metab Cardiovasc Dis 2014;24:408-415.
Article PubMed
59. Bashmakov YK, Assaad-Khalil SH, Abou Seif M, Udumyan R, Megallaa M, Rohoma KH, Zeitoun M, Petyaev IM. Resveratrol promotes foot ulcer size reduction in type 2 diabetes patients. ISRN Endocrinol 2014;2014:816307
Article PubMed PMC
60. Zheng X, Zhu S, Chang S, Cao Y, Dong J, Li J, Long R, Zhou Y. Protective effects of chronic resveratrol treatment on vascular inflammatory injury in steptozotocin-induced type 2 diabetic rats: role of NF-kappa B signaling. Eur J Pharmacol 2013;720:147-157.
Article PubMed
61. Pergola PE, Raskin P, Toto RD, Meyer CJ, Huff JW, Grossman EB, Krauth M, Ruiz S, Audhya P, Christ-Schmidt H, Wittes J, Warnock DG. BEAM Study Investigators. Bardoxolone methyl and kidney function in CKD with type 2 diabetes. N Engl J Med 2011;365:327-336.
Article PubMed
62. de Zeeuw D, Akizawa T, Audhya P, Bakris GL, Chin M, Christ-Schmidt H, Goldsberry A, Houser M, Krauth M, Lambers Heerspink HJ, McMurray JJ, Meyer CJ, Parving HH, Remuzzi G, Toto RD, Vaziri ND, Wanner C, Wittes J, Wrolstad D, Chertow GM. BEACON Trial Investigators. Bardoxolone methyl in type 2 diabetes and stage 4 chronic kidney disease. N Engl J Med 2013;369:2492-2503.
Article PubMed PMC
63. Zhang DD. Bardoxolone brings Nrf2-based therapies to light. Antioxid Redox Signal 2013;19:517-518.
Article PubMed PMC
64. Himmelfarb J, Tuttle KR. New therapies for diabetic kidney disease. N Engl J Med 2013;369:2549-2550.
Article PubMed
65. Li B, Liu S, Miao L, Cai L. Prevention of diabetic complications by activation of Nrf2: diabetic cardiomyopathy and nephropathy. Exp Diabetes Res 2012;2012:216512
Article PubMed PMC
66. Ding Y, Stidham RD, Bumeister R, Trevino I, Winters A, Sprouse M, Ding M, Ferguson DA, Meyer CJ, Wigley WC, Ma R. The synthetic triterpenoid, RTA 405, increases the glomerular filtration rate and reduces angiotensin II-induced contraction of glomerular mesangial cells. Kidney Int 2013;83:845-854.
Article PubMed
67. Hsu WH, Lee BH, Chang YY, Hsu YW, Pan TM. A novel natural Nrf2 activator with PPARgamma-agonist (monascin) attenuates the toxicity of methylglyoxal and hyperglycemia. Toxicol Appl Pharmacol 2013;272:842-851.
Article PubMed
68. Xu J, Kulkarni SR, Donepudi AC, More VR, Slitt AL. Enhanced Nrf2 activity worsens insulin resistance, impairs lipid accumulation in adipose tissue, and increases hepatic steatosis in leptin-deficient mice. Diabetes 2012;61:3208-3218.
Article PubMed PMC
69. Zhang YK, Wu KC, Liu J, Klaassen CD. Nrf2 deficiency improves glucose tolerance in mice fed a high-fat diet. Toxicol Appl Pharmacol 2012;264:305-314.
Article PubMed PMC
70. Rajasekaran NS, Varadharaj S, Khanderao GD, Davidson CJ, Kannan S, Firpo MA, Zweier JL, Benjamin IJ. Sustained activation of nuclear erythroid 2-related factor 2/antioxidant response element signaling promotes reductive stress in the human mutant protein aggregation cardiomyopathy in mice. Antioxid Redox Signal 2011;14:957-971.
Article PubMed PMC
71. Kannan S, Muthusamy VR, Whitehead KJ, Wang L, Gomes AV, Litwin SE, Kensler TW, Abel ED, Hoidal JR, Rajasekaran NS. Nrf2 deficiency prevents reductive stress-induced hypertrophic cardiomyopathy. Cardiovasc Res 2013;100:63-73.
Article PubMed PMC
72. Willis MS, Townley-Tilson WH, Kang EY, Homeister JW, Patterson C. Sent to destroy: the ubiquitin proteasome system regulates cell signaling and protein quality control in cardiovascular development and disease. Circ Res 2010;106:463-478.
Article PubMed PMC
73. Marchan R, Bolt HM. The cytoprotective and the dark side of Nrf2. Arch Toxicol 2013;87:2047-2050.
Article PubMed
74. Grossman R, Ram Z. The dark side of Nrf2. World Neurosurg 2013;80:284-286.
Article PubMed