Combined Iron Chelator and Antioxidant Exerted Greater Efficacy on Cardioprotection Than Monotherapy in Iron-Overloaded Rats.

Abstract

BACKGROUND:

Iron chelators are used to treat iron overload cardiomyopathy patients. However, a direct comparison of the benefits of three common iron chelators (deferoxamine (DFO), deferiprone (DFP) and deferasirox (DFX)) or an antioxidant (N-acetyl cysteine (NAC)) with a combined DFP and NAC treatments on left ventricular (LV) function with iron overload has not been investigated.

METHODS AND FINDINGS:

Male Wistar rats were fed with either a normal diet or a high iron diet (HFe group) for 4 months. After 2 months, the HFe-fed rats were divided into 6 groups to receive either: a vehicle, DFO (25 mg/kg/day), DFP (75 mg/kg/day), DFX (20 mg/kg/day), NAC (100 mg/kg/day) or the combined DFP and NAC for 2 months. Our results demonstrated that HFe rats had increased plasma non-transferrin bound iron (NTBI), malondialdehyde (MDA), cardiac iron and MDA levels and cardiac mitochondrial dysfunction, leading to LV dysfunction. Although DFO, DFP, DFX or NAC improved these parameters, leading to improved LV function, the combined DFP and NAC therapy caused greater improvement, leading to more extensively improved LV function.

CONCLUSIONS:

The combined DFP and NAC treatment had greater efficacy than monotherapy in cardioprotection through the reduction of cardiac iron deposition and improved cardiac mitochondrial function in iron-overloaded rats.

• Authors: Suwakon Wongjaikam, Sirinart Kumfu, Juthamas Khamseekaew, Jirapas Sripetchwandee, Somdet Srichairatanakool, Suthat Fucharoen, Siriporn C Chattipakorn, Nipon Chattipakorn
• Journal: PloS one (PLoS One) Vol. 11 Issue 7 Pg. e0159414 ( 2016) ISSN: 1932-6203 [Electronic] United States
• PMID: 27428732 (Publication Type: Journal Article)

Chemical References

• Benzoates
• Cardiotonic Agents
• Drug Combinations
• Iron Chelating Agents
• Iron, Dietary
• Pyridones
• Triazoles
• Deferiprone
• Malondialdehyde
• Iron
• Deferoxamine
• Deferasirox
• Acetylcysteine

Topics

• Acetylcysteine (pharmacology)
• Animals
• Benzoates (pharmacology)
• Cardiomyopathies (chemically induced, drug therapy, metabolism, pathology)
• Cardiotonic Agents (pharmacology)
• Deferasirox
• Deferiprone
• Deferoxamine (pharmacology)
• Drug Combinations
• Drug Synergism
• Humans
• Iron (blood)
• Iron Chelating Agents (pharmacology)
• Iron Overload (chemically induced, drug therapy, metabolism, pathology)
• Iron, Dietary (adverse effects)
• Male
• Malondialdehyde (blood)
• Mitochondria (drug effects, metabolism)
• Pyridones (pharmacology)
• Rats
• Rats, Wistar
• Triazoles (pharmacology)
• Ventricular Function, Left (drug effects)