Mitochondrial transplantation combined with coenzyme Q10 induces cardioprotection and mitochondrial improvement in aged male rats with reperfusion injury

Abstract Ischaemic heart diseases (IHD) are among the major causes of mortality in the elderly population. Although timely reperfusion is a common treatment for IHD, it causes additional damage to the ischaemic myocardium known as ischaemia–reperfusion (IR) injury. Considering the importance of prev...

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Main Authors: Soleyman Bafadam, Behnaz Mokhtari, Manoucheher Seyedi Vafaee, Zohreh Zavvari Oscuyi, Samira Nemati, Reza Badalzadeh
Format: Article
Language:English
Published: Wiley 2025-05-01
Series:Experimental Physiology
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Online Access:https://doi.org/10.1113/EP091358
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author Soleyman Bafadam
Behnaz Mokhtari
Manoucheher Seyedi Vafaee
Zohreh Zavvari Oscuyi
Samira Nemati
Reza Badalzadeh
author_facet Soleyman Bafadam
Behnaz Mokhtari
Manoucheher Seyedi Vafaee
Zohreh Zavvari Oscuyi
Samira Nemati
Reza Badalzadeh
author_sort Soleyman Bafadam
collection DOAJ
description Abstract Ischaemic heart diseases (IHD) are among the major causes of mortality in the elderly population. Although timely reperfusion is a common treatment for IHD, it causes additional damage to the ischaemic myocardium known as ischaemia–reperfusion (IR) injury. Considering the importance of preventing reperfusion injuries, we aimed to examine the combination effect of mitochondrial transplantation (MT) and coenzyme Q10 (CoQ10) in myocardial IR injury of aged male rats. Seventy‐two aged male Wistar rats were randomly divided into six groups: Sham, IR, CoQ10, MT, combination therapy (MT + CoQ10) and vehicle. Myocardial IR injury was established by occlusion of the left anterior descending coronary artery followed by reopening. Young male Wistar rats were used as mitochondria donors. Isolated mitochondria were injected intraventricularly (500 µL of a respiration buffer containing 6 × 106 ± 5 × 105 mitochondria/mL) in MT‐receiving groups at the onset of reperfusion. CoQ10 (10 mg/kg/day) was injected intraperitoneally for 2 weeks before IR induction. Twenty‐four hours after reperfusion, haemodynamic parameters, myocardial infarct size (IS), lactate dehydrogenase (LDH) release and cardiac mitochondrial function (mitochondrial reactive oxygen species (ROS) generation and membrane potential) were measured. The combination of MT and CoQ10 improved haemodynamic index changes and reduced IS and LDH release (P < 0.05). It also decreased mitochondrial ROS generation and increased membrane potential (P < 0.05). CoQ10 also showed a significant cardioprotective effect. Combination therapy displayed greater cardioprotective effects than single treatments. This study revealed that MT and CoQ10 combination treatment can be considered as a promising cardioprotective strategy to reduce myocardial IR injury in ageing, in part by restoring mitochondrial function.
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spelling doaj-art-587dcd15e03a48a2b54e67a0b51ae7412025-08-20T03:52:11ZengWileyExperimental Physiology0958-06701469-445X2025-05-01110574475410.1113/EP091358Mitochondrial transplantation combined with coenzyme Q10 induces cardioprotection and mitochondrial improvement in aged male rats with reperfusion injurySoleyman Bafadam0Behnaz Mokhtari1Manoucheher Seyedi Vafaee2Zohreh Zavvari Oscuyi3Samira Nemati4Reza Badalzadeh5Molecular Medicine Research Center, Biomedicine Institute Tabriz University of Medical Sciences Tabriz IranDepartment of Physiology, Faculty of Medicine Tabriz University of Medical Sciences Tabriz IranPsychiatry Research Unit Odense DenmarkDepartment of Physiology, Faculty of Medicine Tabriz University of Medical Sciences Tabriz IranPhysiology Research Center Semnan University of Medical Sciences Semnan IranMolecular Medicine Research Center, Biomedicine Institute Tabriz University of Medical Sciences Tabriz IranAbstract Ischaemic heart diseases (IHD) are among the major causes of mortality in the elderly population. Although timely reperfusion is a common treatment for IHD, it causes additional damage to the ischaemic myocardium known as ischaemia–reperfusion (IR) injury. Considering the importance of preventing reperfusion injuries, we aimed to examine the combination effect of mitochondrial transplantation (MT) and coenzyme Q10 (CoQ10) in myocardial IR injury of aged male rats. Seventy‐two aged male Wistar rats were randomly divided into six groups: Sham, IR, CoQ10, MT, combination therapy (MT + CoQ10) and vehicle. Myocardial IR injury was established by occlusion of the left anterior descending coronary artery followed by reopening. Young male Wistar rats were used as mitochondria donors. Isolated mitochondria were injected intraventricularly (500 µL of a respiration buffer containing 6 × 106 ± 5 × 105 mitochondria/mL) in MT‐receiving groups at the onset of reperfusion. CoQ10 (10 mg/kg/day) was injected intraperitoneally for 2 weeks before IR induction. Twenty‐four hours after reperfusion, haemodynamic parameters, myocardial infarct size (IS), lactate dehydrogenase (LDH) release and cardiac mitochondrial function (mitochondrial reactive oxygen species (ROS) generation and membrane potential) were measured. The combination of MT and CoQ10 improved haemodynamic index changes and reduced IS and LDH release (P < 0.05). It also decreased mitochondrial ROS generation and increased membrane potential (P < 0.05). CoQ10 also showed a significant cardioprotective effect. Combination therapy displayed greater cardioprotective effects than single treatments. This study revealed that MT and CoQ10 combination treatment can be considered as a promising cardioprotective strategy to reduce myocardial IR injury in ageing, in part by restoring mitochondrial function.https://doi.org/10.1113/EP091358ageingcoenzyme Q10mitochondrial transplantationmyocardial ischaemia/reperfusion injury
spellingShingle Soleyman Bafadam
Behnaz Mokhtari
Manoucheher Seyedi Vafaee
Zohreh Zavvari Oscuyi
Samira Nemati
Reza Badalzadeh
Mitochondrial transplantation combined with coenzyme Q10 induces cardioprotection and mitochondrial improvement in aged male rats with reperfusion injury
Experimental Physiology
ageing
coenzyme Q10
mitochondrial transplantation
myocardial ischaemia/reperfusion injury
title Mitochondrial transplantation combined with coenzyme Q10 induces cardioprotection and mitochondrial improvement in aged male rats with reperfusion injury
title_full Mitochondrial transplantation combined with coenzyme Q10 induces cardioprotection and mitochondrial improvement in aged male rats with reperfusion injury
title_fullStr Mitochondrial transplantation combined with coenzyme Q10 induces cardioprotection and mitochondrial improvement in aged male rats with reperfusion injury
title_full_unstemmed Mitochondrial transplantation combined with coenzyme Q10 induces cardioprotection and mitochondrial improvement in aged male rats with reperfusion injury
title_short Mitochondrial transplantation combined with coenzyme Q10 induces cardioprotection and mitochondrial improvement in aged male rats with reperfusion injury
title_sort mitochondrial transplantation combined with coenzyme q10 induces cardioprotection and mitochondrial improvement in aged male rats with reperfusion injury
topic ageing
coenzyme Q10
mitochondrial transplantation
myocardial ischaemia/reperfusion injury
url https://doi.org/10.1113/EP091358
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