Therapeutic effects of the combination of moderate-intensity endurance training and MitoQ supplementation in rats with isoproterenol-induced myocardial injury: The role of mitochondrial fusion, fission, and mitophagy

• Published in: Biomedicine & pharmacotherapy Vol. 170; p. 116020
• Main Authors: Rostamzadeh, Farzaneh, Najafipour, Hamid, Aminizadeh, Soheil, Jafari, Elham
• Format: Journal Article
• Language: English
• Published: France Elsevier Masson SAS 01.01.2024; Elsevier
• Subjects: Animals; Cardiac injuries; Dietary Supplements; Endurance Training; Fibrosis; Fission; Fusion; Heart Injuries - chemically induced; Heart Injuries - prevention & control; Humans; Isoproterenol - toxicity; Mitochondria; Mitochondria, Heart; Mitochondrial Dynamics; Mitophagy; MitoQ; Rats; RNA, Messenger; Mitochondria; Endurance training; MitoQ; Fusion; Cardiac injuries; Fission
• ISSN: 0753-3322; 1950-6007
• DOI: 10.1016/j.biopha.2023.116020

Mitochondrial dysfunction causes myocardial disease. This study investigated the effects of MitoQ alone and in combination with moderate-intensity endurance training (EX) on cardiac function and content and mRNA expression of several proteins involved in mitochondrial quality control in isoproterenol (ISO)-induced heart injuries Seven groups of CTL, ISO, ISO-EX, ISO-MitoQ-125, ISO-MitoQ-250, ISO-EX+MitoQ-125, and ISO-EX+MitoQ-250 were assigned. Rats were trained on a treadmill, and the MitoQ groups received MitoQ in drinking water for 8 weeks, starting one week after the induction of heart injury. Arterial pressure and cardiac function indices, mRNA expression, protein content, oxidant and antioxidant markers, fibrosis, and histopathological changes were assessed by physiograph, Real-Time PCR, immunofluorescence, calorimetry, Masson’s trichrome, and H&E staining, respectively. The impacts of MitoQ-125, EX+MitoQ-125, and EX+MitoQ-250 on arterial pressure and left ventricular systolic pressure were higher than MitoQ-250 or EX alone. ± dp/dt max were higher in ISO-EX+MitoQ-125 and ISO-EX+MitoQ-250 than ISO-MitoQ-125 and ISO-MitoQ-250 groups, respectively. Histopathological scores and fibrosis decreased in ISO-EX, ISO-MitoQ-125, ISO-EX+MitoQ-125, and ISO-EX+MitoQ-250 groups. The restoration of MFN2, PINK-1, and FIS-1 changes was higher in ISO-EX+MitoQ-125 and ISO-EX+MitoQ-250 than ISO-EX, ISO-MitoQ-125 and ISO-MitoQ-250 groups. The expression of MFN2 and PINK-1 was lower in ISO-MitoQ-125 and ISO-EX+MitoQ-125 than ISO and CTL groups. The expression of FIS-1 in ISO-EX and ISO-EX+MitoQ-250 increased compared to CTL and ISO groups. MDA decreased in ISO-MitoQ-125 and ISO-EX+MitoQ-125 groups. Exercise and MitoQ combination have additive effects on cardiac function by modulating cardiac mitochondria quality. This study provided a possible therapy to treat heart injuries. [Display omitted] •MitoQ is a scavenger of free radicals condensed in mitochondria.•MitoQ decreases ROS in ISO-induced cardiac injuries.•The combination of MitoQ and exercise modifies fusion, fission, and mitophagy.•Combination therapy reduces cardiac injuries by improving the performance of mitochondria.