Effect of testosterone on cardiac mitochondria after ischemic-reperfusion period.

<p>Testosterone improved cardiac mitochondrial function by showing (A) reduced reactive oxygen species (ROS) production, (B) attenuated mitochondrial swelling and (C) attenuated mitochondrial membrane depolarization in ischemic area. (D) Testosterone also attenuated the deterioration of cardiac mitochondrial morphology. *p < 0.05 vs. Remote area, †p < 0.05 vs. SV group, ‡p < 0.05 vs. OV group. SV = Sham+Vehicle, OV = ORX+Vehicle, ST = Sham+Testosterone, OT = ORX+Testosterone</p

Effect of testosterone replacement on fractional shortening (FS), ejection fraction (EF) and heart rate variability (represent as Low frequency/High frequency ratio: LF/HF ratio) prior I/R injury.

<p>(A, B) Testosterone replacement restored the FS and EF at week 4 and 8, when compared with OV group. (C) Testosterone replacement reduced LF/HF ratio at week 4 and 8, when compared with OV group. *p < 0.05 vs. SV group, †p < 0.05 vs. OV group. SV = Sham+Vehicle, OV = ORX+Vehicle, ST = Sham+Testosterone, OT = ORX+Testosterone.</p

Testosterone and the occurrence of cardiac arrhythmia.

<p>Testosterone replacement did not reduce (A) VT/VF incidence but reduced cardiac arrhythmia by increasing (B) Time to 1^st VT/VF incidence and decreasing (C) arrhythmia score, compared to ORX group. (D) Testosterone increased P-Connexin 43/T-Connexin 43 ratio compared to OV group. *p < 0.05 vs. SV group, †p < 0.05 vs. OV group. SV = Sham+Vehicle, OV = ORX+Vehicle, ST = Sham+Testosterone, OT = ORX+Testosterone. VT = Ventricular tachycardia, VF = Ventricular fibrillation, R = Remote area, I = Ischemic area, CX43 = Connexin 43</p

Summary of blood serum testosterone concentration at week 8.

<p>SV = Sham+Vehicle, OV = ORX+Vehicle, ST = Sham+Testosterone, OT = ORX+Testosterone.</p><p>*p <0.05 vs. SV group</p><p>†p <0.05 vs. OV group.</p><p>Summary of blood serum testosterone concentration at week 8.</p

Diagram illustrated the proposed mechanisms.

<p>The diagram showed the proposed mechanisms of brain dysfunctions as well as the pharmacological therapy on brain dysfunctions following iron overload. Dotted arrows indicate the effects of either L1 or NAC treatment, dashed arrows indicate the combined L1 and NAC treatment. L1: deferiprone; NAC: n-acetyl cysteine.</p

Effects of the pharmacological interventions on body weight, plasma NTBI, plasma MDA, brain MDA and brain iron level in high iron diet-fed rats.

<p>p<0.05 vs. Normal diet-fed rats,</p><p>p<0.05 vs. High iron diet-fed rats treated with vehicle,</p><p>p<0.05 vs. High iron diet-fed rats treated with either L1 or NAC. ND; normal diet-fed rats, HFe; high iron diet-fed rats, V; vehicle, L1; deferiprone, NAC; n-acetyl cysteine, NTBI; non-transferrin bound iron, MDA; malondialdehyde.</p

Effects of iron overload on brain mitochondrial function.

<p>Each panel represented brain mitochondrial ROS production (A), brain mitochondrial membrane potential changes (B) and brain mitochondrial swelling (C). *<i>P</i><0.05 vs. Normal diet groups; ^†<i>P</i><0.05 vs. HFe4w. ND: normal diet fed groups; HFe: high-iron diet fed groups.</p

Effects of the pharmacological interventions by deferiprone and n-acetyl cysteine on BBB breakdown and apoptosis.

<p>Each panel represented the expression of tight junction protein; occludin (A), apoptotic-protein; Bax (B) and anti-apoptotic protein; Bcl-2 (C) and Bax/Bcl-2 ratio (D). *<i>P</i><0.05 vs. Normal diet treated with vehicle (NDV); ^†<i>P</i><0.05 vs. HFe treated with vehicle (HFeV); ^‡<i>P</i><0.05 vs. HFe treated with either L1 or NAC (HFeL1 or HFeNAC). ND: normal diet fed groups; HFe: high-iron diet fed groups; L1: deferiprone; NAC: n-acetyl cysteine.</p

Effects of the pharmacological interventions by deferiprone and n-acetyl cysteine on brain synaptic plasticity.

<p>Each panel represented brain synaptic plasticity in NDV vs. HFeV (A), ND groups (B) and HFe groups (C). ND: normal diet fed group; HFe: high iron diet fed group; L1: deferiprone; NAC: n-acetyl cysteine.</p

Effects of the pharmacological interventions by deferiprone and n-acetyl cysteine on brain mitochondrial function.

<p>Each panel represented brain mitochondrial ROS production (A), brain mitochondrial membrane potential changes (B), brain mitochondrial morphological changes (C) and brain mitochondrial swelling (D). *<i>P</i><0.05 vs. Normal diet treated with vehicle (NDV); ^†<i>P</i><0.05 vs. HFe treated with vehicle (HFeV); ^‡<i>P</i><0.05 vs. HFe treated with either L1 or NAC (HFeL1 or HFeNAC). ND: normal diet fed groups; HFe: high-iron diet fed groups; L1: deferiprone; NAC: n-acetyl cysteine.</p