Table 2.

Studies investigating ROS-producing enzymes in DbCM.

Intervention/Model	Diabetes Model	ROS/Oxidative Stress	Cardiac Structure/Function	Author
MAO inhibitor, Clorgyline [100] or Pargyline [101]	STZ-induced T1D rats	↓ MDA, 4-HNE ↓ MAO-A activity; ↔ MAO-A protein ↓ SOD activity; UCP3 protein; ↑ GSH-Px activity; PRX-3 protein; ↔ CAT activity; PRX-5 protein	↓ contractile dysfunction, diastolic stiffness, electrical abnormalities ↓ morphological changes, fibrosis, apoptosis ↓ mitochondrial depolarization	Umbarkar [100], Deshwal [101]
CM-specific CAPN4 KO or calpastatin-TG	STZ-induced or OVE26 T1D mice	↓ ROS, H2O2; ↔ TAC ↓ NOX, calpain activity	↓ systolic and diastolic dysfunction ↓ cell death ↓ CM hypertrophy ↓ fibrosis, apoptosis	Li [106], Li [107], Ni [109]
NOX inhibitor, Apocynin	STZ-induced T1D mice	↓ O2•− , production, NT, NO ↔ p-eNOS (Ser1177)	↑ systolic function ↔ cardiac remodeling ↑ CM contractility	Roe [122]
NOX4 ASOs	STZ-induced T1D rats	↓ NOX4; ↔ NOX1, NOX2 protein ↓ ROS (DHE), NOX-dependent O2•− production	↓ systolic dysfunction ↓ cardiac fibrosis	Maalouf [125]
CM-specific RAC1 KO or NOX inhibitor, Apocynin	STZ-induced T1D mice	↓ O2•− , H2O2 production, total/mitochondrial ROS production ↓ Rac1 mRNA/protein/activity; membrane Rac1, p67phox protein; NOX activity; Rac1, gp91phox, p67phox, p47phox mRNA ↑ TRXR activity	↓ cardiac dysfunction ↓ CM hypertrophy ↓ cardiac fibrosis, apoptosis	Li [124], Shen [121]
XO inhibitor, Allopurinol	STZ-induced T1D mice/rats	↓ ROS, 3-NT, 15-f2t-isoprostane ↓ SOD activity; MnSOD, iNOS protein, XO protein/activity; ↔ eNOS protein ↔ p22phox, p40phox, p47phox and gp91phox mRNA expression ↑ NRF2 mRNA/nuclear protein; ↓ Keap1 protein/mRNA	↓ systolic & diastolic dysfunction ↓ cardiac remodeling & hypertrophy ↓ atrial CM disorder ↓ atrial & LV fibrosis, apoptosis	Yang [128], Rajesh [130], Gao [131], Luo [132]
eNOS, iNOS and nNOS KO or BH4 precursor, Sepiapterin	STZ- induced T1D mice	iNOS−/−: ↓ MDA, 4-HNE, NT protein ↓ NOx bioavailability sepiapterin: ↓ MDA, 4-HNE, NT protein ↑ BH4 and the BH4/BH2 ratio ↓ NOx bioavailability	sepiapterin: ↑ systolic function ↓ cardiac remodeling	Jo [144]