Role of Oxidative Stress in Thyroid Hormone-Induced Cardiomyocyte Hypertrophy and Associated Cardiac Dysfunction: An Undisclosed Story

Table 2

Effects of antioxidants or drugs protecting against oxidative stress on thyroid hormone-induced cardiac hypertrophy and associated cardiac dysfunction.

Drug	Mechanism	Cardiac hypertrophy	Cardiac dysfunction	Reference
Vitamin E	Inhibits lipid peroxidation independent of changes in oxidative or antioxidant enzymes	No change	NA	[25]
	Inhibits lipid peroxidation and increased total antioxidant capacity	No change	Partially improved shortened APD of isolated RVPM in vitro	[52, 53]
	Inhibits lipid and protein oxidation and attenuates changes in oxidative, antioxidative enzymes and related signaling for example IGF-I, AKT, ERK 1/2, NADPH-oxidase, NOS, and AT1R	Decrease	Normalization of ventricular (+/−) and inhibition of organ (liver and lung) congestion, which is a marker of heart failure	[19, 20, 22, 23]
Atenolol	β-blocker suppresses mitochondrial hypermetabolism and oxidative stress	No change	NA	[44]
NAC	Antioxidant inhibits lipid peroxidation and increases total antioxidant capacity	No change	Partially improved shortened APD of isolated RVPM in  vitro	[53]
Cholesterol	Inhibits lipid peroxidation	No change	No change
L-NAME	Nonspecific inhibitor of all NOS isoforms (eNOS, iNOS, and nNOS)	No change	NA	[27]
AG	Specific inhibitor of iNOS	No change	NA	[28]
7-NI	Specific inhibitor of nNOS	No change	NA	[29]
Tempol	Cell membrane-permeable low-molecular-weight SOD mimetic drug	No change	NA	[26]
Carvedilol	Mixed α, β-blocker with antioxidant activities	No change	NA	[55]
Pravastatin	Inhibits active Rac1, a major component of NADPH-oxidase complex	No change	No change	[17]
Allopurinol	Xanthine-oxidase inhibitor	No change	No change	[56]
Apocynin	NADPH-oxidase inhibitor	No change	Significant increase in LV EF and FS
L-NIO	Nonspecific inhibitor of all NOS isoforms (eNOS, iNOS, and nNOS)	No change	Strong trend to increase LV EF and FS but did not reach significance
Mito-TEMPO	Mitochondria-targeted antioxidant	No change	No change

APD: action potential duration; RVPM: right ventricular papillary muscle; IGF-1: insulin-like growth factor-1; ERK: extracellular regulated kinase; NADPH: nicotinamide adenine dinucleotide phosphate; NOS: nitric oxide synthase; AT1R: angiotensin receptor type-1; +: positive pressure derivative; −: negative pressure derivative; NAC: N-acetylcysteine; eNOS: endothelial nitric oxide synthase; iNOS: inducible nitric oxide synthase; nNOS: neuronal nitric oxide synthase; L-NAME: N^w-nitro-L-arginine methyl ester; AG: aminoguanidine; 7-NI: 7-nitroindazole; SOD: superoxide dismutase; L-NIO: N⁵-(1-iminoethyl)-L-ornithine dihydrochloride; Mito-TEMPO: (2-(2,2,6,6-tetramethylpiperidin-1-oxyl-4-ylamino)-2-oxoethyl) triphenylphosphonium chloride; LV: left ventricular; EF: ejection fraction; FS: fractional shortening; no change in gross heart weight or heart weight/body weight, but there was a partial but significant decrease in cardiomyocyte size; NA: not assessed.