Table 3.

Studies investigating the antioxidant defense system in DbCM.

Intervention/Model	Diabetes Model	ROS/Oxidative Stress	Cardiac Structure/Function	Author
MnSOD-TG	OVE26 T1D mice genetic lipid overload-induced T2D mice	↑ cardiac SOD activity ↑ mitochondrial MnSOD protein ↑ CAT protein/activity, GSH protein ↓ cardiomyocyte ROS ↓ mitochondrial H₂O₂, 4-HNE	↑ RCR, state 3 respiration ↓ mitochondrial mass/number; ↑ mitochondrial function ↑ CM contractility ↓ mitochondrial size ↑ mitochondrial fission	Shen [31] Tsushima [89]
CM-specific CAT-TG	STZ-induced T1D mice OVE26 T1D mice	↓ ROS, H₂O₂, MPO, 3-NT of α-KGD, ATP-α and ATP-β ↓ iNOS protein; ↔ eNOS protein ↑ SIRT2 protein ↓ MDA; CM ROS	↓ systolic & diastolic cardiac dysfunction ↓ CM contractile dysfunction ↓ LV hypertrophy ↓ myocardial disorder ↓ cardiac fibrosis, apoptosis ↓ mitochondrial damage ↑ CM contractility	Cong [182], Turdi [183] Ye [29]
mPHGPx-TG	STZ-induced T1D mice	↓ H₂O₂ production, 4-HNE, MDA in IFM	↓ systolic dysfunction ↑ ATP synthase activity in IFM ↑ mitochondrial respiration ↓ mitochondrial dysfunction	Baseler [185]
GSHPx-TG	STZ-induced T1D mice	↓ TBARS, 4-HNE ↑ GSH-Px; ↔ SOD, CAT activities	↓ CM hypertrophy ↓ fibrosis ↓ apoptosis	Matsushima [186]
TRX2 activation or TRXR inhibitors, Auranofin & CDNB	STZ-induced T1D mice	↓ ROS ↓ PRX-SO2/3H; ↔ TRX1 expression/localization	↓ CM hypertrophy ↓ contractile dysfunction	Li [190]
CM-specific TXNIP KO	STZ-induced T1D mice	↔ ROS	↔ LV hypertrophy, cardiac function ↑ inotropic reserve	Myers [194]
GSH precursor, NAC	STZ-induced T1D mice	↓ ROS, H₂O₂, TAS, NO ↑ GSH content	↓ systolic & diastolic dysfunction ↓ LV hypertrophy ↓ fibrosis, apoptosis ↑ myofilament morphology	Liu [199], Fiordaliso [200], Yildirim [201]
CM-specific MT-TG	OVE26 T1D mice STZ-induced T1D mice	↓ GSSG; ↔ GSH ↓ $O_{2}^{• -}$ , ROS, 3-NT; 3-NT of ATP synthase α ↓ Trp374/Tyr135 nitration of SCOT ↑ p47(phox)	↓ myocardial injury ↓ CM contractile dysfunction; LV dysfunction/stiffness ↓ myocardial structural derangement ↓ fibrosis, necrosis ↑ ATP synthase, SCOT activity	Liang [50] Wold [113], Cai [264], Cong [213], Cong [214]
SIRT3 KO mice	STZ-induced T1D mice	↑ ROS	↑ cardiac dysfunction ↑ necrosis ↓ ATP	Song [223]
NRF2 KO	STZ-induced T1D mice HFD/STZ-induced T2D mice	↑ 8-OHdG, MDA, 3-NT, 4-HNE ↓ NRF2, NQO1 mRNA ↑ ROS production ↓ NRF2, NQO1, HO1 mRNA/protein ↓ total, nuclear NRF2 protein ↑ 8-OHdG, MDA ↓ NQO-1, HO-1, MT mRNA; MT protein	↓ cardiac dysfunction ↓ CM hypertrophy, myocardial structural damage ↓ CM contractility ↑ fibrosis, apoptosis ↑ CM hypertrophy ↓ systolic function ↑ fibrosis	He [257], He [237], Zang [301] Gu [239]
CM-specific NRF2-TG mice	STZ-induced T1D mice	↑ 4-HNE, 8-OHdG	↑ cardiac dysfunction ↑ fibrosis, apoptosis	Zang [301]
NRF2 activator, Dh404	STZ-induced T1D mice	↑ NRF2 protein ↓ 3-NT		Tan [233]
HO-1-TG mutHO-1-TG	STZ-induced T1D mice	HO-1-TG: ↓ p47phox, GSH-PX3 mRNA) mutHO-1-TG: ↑ p47phox, GSH-Px3 mRNA	HO-1-TG: ↓ systolic dysfunction mutHO-1-TG: ↑ apoptosis	Zhao [240]
ALDH2-TG	sucrose-fed pre-T2D mice	↑ SIRT3, HO-1 protein ↓ ROS	↓ myocardial dysfunction ↑ CM contractility ↑ intracellular Ca2+ handling ↑ NAD + activity	Hu [252]