Cardioprotective effect of antioxidant combination therapy: A highlight on MitoQ plus alpha-lipoic acid beneficial...

Area of Science:

• Cardiovascular Research
• Aging Biology
• Mitochondrial Medicine

Background:

• Ischemic heart disease poses a poor prognosis, especially in the elderly.
• Existing cardioprotective strategies show diminished efficacy in aged populations.
• Aging exacerbates myocardial ischemia/reperfusion injury (IRI) outcomes.

Purpose of the Study:

• To investigate the protective effects of mitoquinone (MitoQ) and alpha-lipoic acid (ALA) preconditioning in aged rats.
• To assess the impact of combined MitoQ and ALA therapy on myocardial IRI.
• To evaluate the interaction of aging with cardioprotection during IRI.

Main Methods:

• Aged male Wistar rats underwent a 30-minute coronary artery ligation followed by 24-hour reperfusion (IRI model).
• Animals received daily oral ALA (100 mg/kg) and/or intraperitoneal MitoQ (10 mg/kg) for 14 days.
• Evaluated oxidative stress, mitochondrial function, gene expression (Mfn1, Mfn2, Foxo1, Drp1, Fis1), infarct size, hemodynamics, and LDH levels.

Main Results:

• Combined MitoQ and ALA significantly reduced oxidative stress, LDH levels, and myocardial infarct size.
• Mitochondrial function was enhanced, with upregulated Mfn1, Mfn2, Foxo1 and downregulated Drp1, Fis1 gene expression.
• Co-administration partially restored IRI-induced hemodynamic changes, showing superior efficacy over monotherapies.

Conclusions:

• Combination therapy with MitoQ and ALA offers significant therapeutic potential for protecting the aging heart against IRI.
• The treatment effectively improves oxidative stress, mitochondrial function, and mitochondrial dynamics in aged hearts.
• This combined approach represents a promising strategy for cardioprotection in the context of aging.