Table 1.
Summary of pre‐clinical and clinical trials using anti‐oxidative stress treatments
| Experimental animal studies | Target | Treatment | Model | Results | Ref. |
|---|---|---|---|---|---|
| Inhibition of oxidative stress producers | NADPH oxidase | Cytosolic NADPH oxidase component p47phox knock‐out | MI mice | Protected the heart from LV remodelling and dysfunction post‐MI | 32 |
| Xantine oxidase | Oxypurinol administration | Spontaneous hypertensive/HF (SHHF) rat | Improved LV contractility and myocardial efficiency | 33 | |
| Allopurinol administration | Exercise‐induced HF in dogs | In pacing‐induced CHF, allopurinol improved LV systolic function | 34 | ||
| NOS uncoupling | Sapropterin administration | Chronic transverse aortic constriction mice | Improved cardiac function | 12 | |
| Improving endogenous antioxidant capacity | SOD | SOD overexpression | Ischaemia/reperfusion injury in mice | Reduced oxidative stress production, improved contractility, and reduced infarct size | 35 |
| Catalase | Catalase overexpression | Myocyte‐specific overexpression of G(alpha)q mice (a model for dilated cardiomyopathy) crossbred with myocyte‐specific overexpression of catalase | Reduced myocyte hypertrophy, myocyte apoptosis, and fibrosis | 36 | |
| GPx | GPx overexpression | MI mice | Prevention of adverse LV remodelling | 18 | |
| Ischaemia/reperfusion injury in mice | Improved contractility and reduced infarct size | ||||
| GSH | N‐acetylcysteine administration | MI rats | Improved LV GSH levels, improved contractility, and reduced LV remodelling | 28 | |
| Hypertensive rat model (induced by NOS inhibitor N(G)‐nitro‐L‐arginine methyl ester and high‐salt diet) | Improved cardiac GSH levels, reduced LV remodelling and dysfunction, improved TNF‐α levels, and reduced cardiac fibrosis | 29 | |||
| NAD+ | Nicotamide riboside administration | Mouse model of dilated cardiomyopathy | Improved cardiac function and redox state | 26 | |
| Supplementation of exogenous antioxidants | ROS | Vitamin E supplementation | Ascending aortic banding in guinea pigs (cardiac hypertrophy) | Improved myocardial redox state and cardiac function | 37 |
| Diabetic rat model by injection of streptozotocin | Improved myocardial redox state and cardiac function | 38 | |||
| Volume overload dog model | Reduced oxidative stress and improved myocardial contractility | 39 | |||
| Folic acid supplementation | Mouse model of high‐fat diet‐induced obesity | Reduced cardiac dysfunction, oxidative stress, and myocardial fibrosis | 40 | ||
| Inhibition of oxidative stress producers | Xanthine oxidase | Oxypurinol administration | Chronic HF (n = 60) | Improved LV ejection fraction | 41 |
| Symptomatic HF (n = 405) | No improved clinical outcome | 42, 43 | |||
| Allopurinol administration | Idiopathic dilated cardiomyopathy (n = 9) | Improved myocardial efficiency | 11 | ||
| Chronic HF (n = 50) | Reduced plasma BNP levels | 44 | |||
| Primary percutaneous transluminal coronary angioplasty in patients with acute MI (n = 38) | Reduced oxidative stress and improved LV function | 45 | |||
| Hyperuricaemic chronic HF (n = 19) | Improved peripheral vasodilator capacity and blood flow locally and systemically | 46 | |||
| Chronic HF (n = 11) | Improved endothelial dysfunction | 47 | |||
| NOS uncoupling | Sapropterin administration | Coronary artery disease (n = 49) | No effect on vascular function or redox state | 48 | |
| Improving endogenous antioxidant capacity | GSH | N‐acetylcysteine administration | Acute MI (n = 30) | Improved cardiac function | 49 |
| N‐acetylcysteine and streptokinase administration | Acute MI (n = 1, case study) | Improved cardiac function | 50 | ||
| N‐acetylcysteine, nitroglycerin and streptokinase administration | Acute MI (n = 27) | Reduced oxidative stress and improved LV function | 51 | ||
| Supplementation of exogenous antioxidants | ROS | Vitamin E supplementation | Ischaemic heart disease (n = 2002) | Reduced rate of non‐fatal MI | 52 |
| Combined vitamin A, C, E, and β‐carotene | Suspected acute MI (n = 125) | Reduced cardiac necrosis and oxidative stress | 53 | ||
| Meta‐analysis of randomized controlled trials | Cardiovascular diseases (50 studies, n = 294 478), including coronary heart disease, acute MI, unstable angina, TIA, stroke, and angiographically proved coronary atherosclerosis | No beneficial effects of vitamin supplementation on preventing cardiovascular disease | 54 |
BNP, B‐type natriuretic peptide; CHF, congestive heart failure; GPx, glutathione peroxidase; GSH, glutathione; HF, heart failure; LV, left ventricle; MI, myocardial infarction; NAD+, nicotinamide adenine dinucleotide; NOS, nitric oxide synthase; SOD, superoxide dismutase; ROS, reactive oxygen species; TIA, transient ischaemic attack; TNF, tumour necrosis factor.