Table 1.

Results of the use of Vit C alone or in association with other antioxidants.

Model	Dose	Results	Ref.
Human Models
Human (in vivo)	16.6 mg/min, over 1 h before PCI	Better preservation of CF No changes in HR, cTnT and MAP Better perfusion ↓ CK-MB levels ↓ Oxidative stress	[65]
Human (in vivo)	500 mg, twice a day for 5 days before analysis	↑ SOD activity ↑ Thiol levels ↓ XO activity ↓ MDA	[63]
Human (in vivo)	Multivitamin therapy Before reperfusion: Vit C, 1 g in IV bolus. After reperfusion (daily, for 1 month, via oral): Vit C 1 g, Vit A 50,000 Unit, Vit E 300 mg	Better preservation of cardiac function ↓ Oxidative stress ↑ Antioxidant status	[16]
Human (in vivo)	Initial dose of 2000 mg followed by a constant infusion at 20 mg/min before PCI	No suppression of oxidative stress	[68]
Human (in vivo)	1 g/L at 24 mg/min IV infusion	Better preservation of CF cTnT was similar between control and Vit C group ↓ Oxidative stress	[66]
Human (in vivo)	IV infusion of 320 mM at a flow rate of 10 mL/min during the initial hour and at 3 mL/min during the following 2 h. After the primary PCI, oral doses of Vit C (500 mg/12 h) and α-tocopherol (400 IU/day) for 84 continuous days	No significant difference in infarct size between the groups Better preservation of CF No changes in CK-MB ↑ FRAP levels	[69]
Human (in vivo)	Initial dose of 3 g IV before PCI and 100 mg of intracoronary Vit C during PCI	↓cTnT and CK-MB levels	[73]
Human (in vivo)	Initial unique oral dose of α-tocopherol (800 IU) and IV infusion of Vit C (320 mM) infused at a 10 mL/min flow rate during the first hour and at a 3 mL/min rate during the following 2 h. After the PCI, oral doses of Vit E (400 IU/day) and Vit C (500 mg/12 h) were taken by the patients for 84 continuous days.	Better preservation of CF No differences in CK-MB ↑ FRAP levels	[64]
Human (in vivo)	3 g IV within 6 h before PCI	↓ cTnT and CK-MB levels ↓ Oxidative stress	[67]
Animal models
Adult mongrel dogs (in vivo)	100 mg/kg of Vit C was administered just before reperfusion	↓ Mortality in group of supplemented dogs ↑ GSH/GSSG ratio No significant changes in activities of GPX and GR	[91]
Domestic pigs (in vivo)	Combined treatment of 4.4 g of Vit C (about 0.1 gm/kg) and 12 g of Vit E acetate was infused	↓ Infarct size, but just reached the border of significance	[92]
Langendorff model using isolated rat hearts (ex vivo)	At the time of reperfusion one group was infused with 1 mM of AA and another group with 1 mM of AA plus 1 mM of GSHme	AA Slightly ↓ myocardial TBAR contents	[93]
		AA plus GSHme ↑ GSH content HR and CF were recovered ↓ Incidence of VF ↓ Myocardial CK loss ↓ Myocardial TBARS content ↓ Myocardial nitrotyrosine
Young male farm pigs (in vivo)	IV infusion of 100 mg/kg AA and 60 mg/kg DFO	The therapy did not provide significant cardioprotection in the experimental group in any of the parameters measured	[94]
Farm-raised domestic male pigs (in vivo)	One group receive AA 100 mg/kg infusion. Other group receive AA 100 mg/kg + DFO 60 mg/kg + NAC 100 mg/kg for 20 min with a 20-mg/kg maintenance dose	The therapy did not provide significant cardioprotection in the experimental group in any of the parameters measured	[95]
Langendorff model using isolated male Sprague-Dawley rats hearts (ex vivo)	Hearts were post-treated with 2 μM Vit C for 30 min after global ischemia	↓ I/R-Induced infarct area ↓ LDH activity Improved all hemodynamic variables ↑ NAD+, suggested that Vit C inhibited mPTP opening ↓ Apoptosis ↑ Oxygen consumption	[96]
Cell Cultures
HeLa and MCF7 cells (in vitro)	HeLa cells incubated with 1 mM DHA for 1 h and accumulated 4 mM intracellular Vit C. Conversely, cells incubated with 1 mM Vit C for 1 h accumulated 0.2 mM intracellular Vit C *	Inhibits: TNFα-induced transcriptional responses mediated by NF-κB TNF-dependent nuclear translocation of NF-κB The TNFα-induced phosphorylation and degradation of IκBR	[77]
Neonatal rat cardiac fibroblast (in vitro)	Cells treated with Vit C in doses of 1 μM, 10 μM 100 μM, 10,000 μM	No effect in cell viability at 1 and 10 μM ↑ Cell viability but not significantly at 100 μM ↓ Cell viability at 10,000 μM	[97]
	Cells treated with different combinations of Vit C, DFO, NAC (Vit C/DFO, Vit C/NAC and Vit C/NAC/DFO), each in doses of 1 and 10 μM	↑ Cell viability only Vit C/DFO in doses of 1 μM ↑ Cell viability Vit C/DFO, Vit C/NAC and Vit C/NAC/DFO in doses of 10 μM ↓ Intracellular ROS production Vit C/NAC/DFO in doses of 10 μM
HUVEC HCAEC (in vitro)	Cells were preloaded with AA by incubating with different concentrations of DHA for 30 min before subjecting to hypoxia	↓ Apoptosis ↓ ROS levels Prevents release of Cyt C to cytosol Stabilizes mitochondrial membrane potential Inhibits procaspase-9 and procaspase-3 activation	[98]
Neonatal rat cardiac ventricular myocytes (in vitro)	Cells were post-conditioned with normal culture medium containing 2 μM Vit C	↑ Cell viability ↓ LDH activity ↓Cytosolic Ca2+ overload. ↓ ROS levels Alleviated mPTP opening in cardiomyocytes Preserved ΔΨm ↑ AKT (Ser473) phosphorylation ↑ Expression of p-GSK 3β(Ser9)	[96]

* Probably due to conversion of Vit C to DHA under aerobic conditions: AA, ascorbic acid; CF, cardiac function; CK-MB, creatinine phosphokinase MB isoenzyme; cTnT, cardiac troponin; Cyt c, citocrome C; DHA, dehydroascorbic acid; DFO, deferoxamine; FRAP, ferric reducing ability of plasma; GPX, glutathione peroxidase; GR, glutathione reductase; GSH, reduced glutathione; GSSG, glutathione disulfide; HR, heart rate; IV, intravenously; LDH, lactate dehydrogenase; MAP, mean arterial pressure; MDA, malondialdehyde; mPTP, mitochondrial permeability transition pore; NAC, N-acetylcysteine; PCI, percutaneous coronary intervention; ROS, reactive oxygen species; SOD, superoxide dismutase; TBAR, thiobarbituric acid reactive substances; TNF, tumor necrosis factor; Vit A, vitamin A; Vit C, vitamin C; Vit E, vitamin E; XO, xanthine oxidase; ΔΨm, mitochondrial membrane potential; ↑, increase; ↓, decrease.