Fig 1.
The summary of the experimental protocol.
ND = normal diet group; HFe = high iron diet group; V = vehicle; DFO = deferoxamine; DFP = deferiprone; DFX = deferasirox; NAC = N-acetyl cysteine; NTBI = non-transferrin bound iron; MDA = malondialdehyde; ROS = reactive oxygen species; ΔΨm = membrane potential change.
Fig 2.
Combined DFP+NAC treatment could decrease plasma NTBI and MDA levels as well as restore normal cardiac iron and MDA content in iron-overloaded rats.
The effects of the pharmacological interventions on: (A) plasma non-transferrin bound iron (NTBI) level; (B) plasma malondialdehyde (MDA) content; (C) cardiac iron concentration and (D) cardiac MDA content in iron-overloaded rats. *P < 0.05 vs. control, †P < 0.05 vs. HFe, ‡P < 0.05 vs. HFeDFP+NAC.
Table 1.
The effects of the pharmacological interventions on blood pressure parameters in iron-overloaded rats.
Fig 3.
Chronic iron overloaded impaired heart rate variability and decreased cardiac function in iron-overloaded rats.
The effects of the iron overload condition on: (A) heart rate variability at baseline, 2, 3 and 4 months, and (B) the percentage of left ventricular fractional shortening (%LVFS) measured using echocardiography at baseline, 2, 3 and 4 months in iron-overloaded rats. *P < 0.05 vs. control, †P < 0.05 vs. HFe diet for 2 months, ‡P < 0.05 vs. HFe diet for 3 months.
Fig 4.
Combined DFP+NAC treatment could restore heart rate variability and cardiac function in iron-overloaded rats.
The effects of the pharmacological interventions on heart rate variability at 3 months (A), and 4 months (B), and the percentage of left ventricular fractional shortening (%LVFS) measured using echocardiography at 3 months (C), and 4 months (D) in iron-overloaded rats. *P < 0.05 vs. control, †P < 0.05 vs. HFe, ‡P < 0.05 vs. HFeDFP+NAC.
Table 2.
The effects of the pharmacological interventions on hemodynamic parameters in iron-overloaded rats.
Fig 5.
Combined DFP+NAC treatment could restore cardiac mitochondrial function in iron-overloaded rats.
The effects of the pharmacological interventions on: (A) cardiac mitochondrial reactive oxygen species (ROS) production; (B) cardiac mitochondrial membrane potential change and (C) cardiac mitochondrial swelling in iron-overloaded rats. *P < 0.05 vs. control, †P < 0.05 vs. HFe, ‡P < 0.05 vs. HFeDFP+NAC.
Fig 6.
Electron micrographs of cardiac mitochondria from control, HFeV, HFeDFO, HFeDFP, HFeDFX, HFeNAC and HFeDFP+NAC groups.
Iron-overloaded rats led to dysmorphic morphology and swelling of cardiac mitochondria compared to the control group. All of the pharmacological interventions could restore cardiac mitochondrial morphology which was obtained by using a transmission electron microscope in iron-overloaded rats.
Fig 7.
Diagram illustrating the proposed mechanisms of chronic iron overload on cardiac dysfunction and the effects of all pharmacological interventions on cardiac dysfunctions caused by chronic iron overload.
Dashed arrows indicate the effects of either DFO, DFP, DFX or NAC treatment; solid arrows indicate the effects of combined DFP plus NAC treatment. DFO = deferoxamine; DFP = deferiprone; DFX = deferasirox; NAC = N-acetyl cysteine; NTBI = non-transferrin bound iron; MDA = malondialdehyde.