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

Area of Science:

• Cardiology
• Pharmacology
• Toxicology

Background:

• Iron overload cardiomyopathy poses a significant clinical challenge.
• Current iron chelators (deferoxamine, deferiprone, deferasirox) and antioxidants (N-acetyl cysteine) have shown benefits, but their comparative efficacy and combined effects are not fully understood.
• Left ventricular function is a critical indicator of cardiac health in iron overload conditions.

Purpose of the Study:

• To directly compare the efficacy of deferoxamine (DFO), deferiprone (DFP), and deferasirox (DFX), and N-acetyl cysteine (NAC) in treating iron overload-induced left ventricular (LV) dysfunction.
• To investigate the effects of a combined DFP and NAC treatment versus monotherapy on LV function in iron-overloaded rats.

Main Methods:

• Male Wistar rats were subjected to a high-iron diet for 4 months to induce iron overload.
• After 2 months, rats received vehicle, DFO, DFP, DFX, NAC, or combined DFP and NAC for 2 months.
• Evaluated plasma non-transferrin bound iron (NTBI), malondialdehyde (MDA), cardiac iron and MDA levels, cardiac mitochondrial function, and LV function.

Main Results:

• High-iron diet induced increased NTBI, MDA, cardiac iron, and mitochondrial dysfunction, leading to LV dysfunction.
• All tested monotherapies (DFO, DFP, DFX, NAC) demonstrated improvements in these parameters and LV function.
• Combined DFP and NAC therapy resulted in significantly greater improvements in cardiac parameters and LV function compared to monotherapies.

Conclusions:

• Combined deferiprone and N-acetyl cysteine treatment exhibits superior efficacy in cardioprotection compared to monotherapy.
• This combination therapy effectively reduces cardiac iron deposition and enhances cardiac mitochondrial function in iron-overloaded conditions.
• The findings suggest a promising therapeutic strategy for managing iron overload cardiomyopathy.