Diminazine protects against cardiac aging through the improvement of mitophagy and apoptosis in aging rats induced by D-galactose

Abstract Background Mitochondrial dysfunction is a main feature of the aged heart. However, there is still no effective treatment against cardiac aging. Diminazine (DIZE) is an anti-infective agent for animals. It is effective against cardiac disorders. The present study aimed to investigate the eff...

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Main Authors: Ensiyeh Velayati, Abdolrahman Sarihi, Mohammad Zarei, Alireza Komaki, Fatemeh Ramezani-Aliakbari
Format: Article
Language:English
Published: BMC 2025-02-01
Series:BMC Cardiovascular Disorders
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Online Access:https://doi.org/10.1186/s12872-025-04572-4
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author Ensiyeh Velayati
Abdolrahman Sarihi
Mohammad Zarei
Alireza Komaki
Fatemeh Ramezani-Aliakbari
author_facet Ensiyeh Velayati
Abdolrahman Sarihi
Mohammad Zarei
Alireza Komaki
Fatemeh Ramezani-Aliakbari
author_sort Ensiyeh Velayati
collection DOAJ
description Abstract Background Mitochondrial dysfunction is a main feature of the aged heart. However, there is still no effective treatment against cardiac aging. Diminazine (DIZE) is an anti-infective agent for animals. It is effective against cardiac disorders. The present study aimed to investigate the effects of DIZE on age-related cardiac dysfunction. Methods and results Wistar rats were randomly divided into four groups, with eight rats per group: control rats (CONT), control rats treated with DIZE (CONT + DIZE), aged rats induced by D-galactose (D-GAL), aged rats treated with DIZE (D-GAL + DIZE). Rats received intraperitoneal (IP) injection of D-GAL at 150 mg/kg daily for 8 weeks to induce aging. The aging animals in the D-GAL + DIZE group were treated with subcutaneous injection of DIZE at 15 mg/kg daily for 8 weeks. Heart tissues were harvested to assay molecular parameters. Our results exhibited cardiac hypertrophy and a significant increase in the expression of cardiac BCL2-associated X (Bax) along with a significant decrease in the expression of cardiac Mitofusin 2 (Mfn2), Phosphatase, and tensin homolog (PTEN)-induced putative kinase 1 (PINK1), Dynamin-related protein 1 (Drp1), and B-cell lymphoma 2 (Bcl2) in the aged rats compared with the control animals. DIZE treatment improved cardiac hypertrophy and the expression of genes. Conclusions Overall, DIZE treatment significantly reversed the downregulation of PINK1, Mfn2, and Drp1. Moreover, DIZE significantly inhibited apoptosis though improving the gene expression of Bax and Bcl-2 in the heart. DIZE is effective in reducing cardiac hypertrophy induced aging through regulating mitochondrial dynamics, mitophagy and apoptosis.
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spelling doaj-art-42e610280bc34a19a50de3d7eabe3b6e2025-08-20T02:15:07ZengBMCBMC Cardiovascular Disorders1471-22612025-02-012511910.1186/s12872-025-04572-4Diminazine protects against cardiac aging through the improvement of mitophagy and apoptosis in aging rats induced by D-galactoseEnsiyeh Velayati0Abdolrahman Sarihi1Mohammad Zarei2Alireza Komaki3Fatemeh Ramezani-Aliakbari4Department of Physiology, School of Medicine, Hamadan University of Medical SciencesNeurophysiology Research Center, Institute of Neuroscience and Mental Health, Avicenna Health Research Institute, Hamadan University of Medical SciencesDepartment of Physiology, School of Medicine, Hamadan University of Medical SciencesNeurophysiology Research Center, Institute of Neuroscience and Mental Health, Avicenna Health Research Institute, Hamadan University of Medical SciencesDepartment of Physiology, School of Medicine, Hamadan University of Medical SciencesAbstract Background Mitochondrial dysfunction is a main feature of the aged heart. However, there is still no effective treatment against cardiac aging. Diminazine (DIZE) is an anti-infective agent for animals. It is effective against cardiac disorders. The present study aimed to investigate the effects of DIZE on age-related cardiac dysfunction. Methods and results Wistar rats were randomly divided into four groups, with eight rats per group: control rats (CONT), control rats treated with DIZE (CONT + DIZE), aged rats induced by D-galactose (D-GAL), aged rats treated with DIZE (D-GAL + DIZE). Rats received intraperitoneal (IP) injection of D-GAL at 150 mg/kg daily for 8 weeks to induce aging. The aging animals in the D-GAL + DIZE group were treated with subcutaneous injection of DIZE at 15 mg/kg daily for 8 weeks. Heart tissues were harvested to assay molecular parameters. Our results exhibited cardiac hypertrophy and a significant increase in the expression of cardiac BCL2-associated X (Bax) along with a significant decrease in the expression of cardiac Mitofusin 2 (Mfn2), Phosphatase, and tensin homolog (PTEN)-induced putative kinase 1 (PINK1), Dynamin-related protein 1 (Drp1), and B-cell lymphoma 2 (Bcl2) in the aged rats compared with the control animals. DIZE treatment improved cardiac hypertrophy and the expression of genes. Conclusions Overall, DIZE treatment significantly reversed the downregulation of PINK1, Mfn2, and Drp1. Moreover, DIZE significantly inhibited apoptosis though improving the gene expression of Bax and Bcl-2 in the heart. DIZE is effective in reducing cardiac hypertrophy induced aging through regulating mitochondrial dynamics, mitophagy and apoptosis.https://doi.org/10.1186/s12872-025-04572-4AgingApoptosisCardiac hypertrophyDiminazineMitophagy
spellingShingle Ensiyeh Velayati
Abdolrahman Sarihi
Mohammad Zarei
Alireza Komaki
Fatemeh Ramezani-Aliakbari
Diminazine protects against cardiac aging through the improvement of mitophagy and apoptosis in aging rats induced by D-galactose
BMC Cardiovascular Disorders
Aging
Apoptosis
Cardiac hypertrophy
Diminazine
Mitophagy
title Diminazine protects against cardiac aging through the improvement of mitophagy and apoptosis in aging rats induced by D-galactose
title_full Diminazine protects against cardiac aging through the improvement of mitophagy and apoptosis in aging rats induced by D-galactose
title_fullStr Diminazine protects against cardiac aging through the improvement of mitophagy and apoptosis in aging rats induced by D-galactose
title_full_unstemmed Diminazine protects against cardiac aging through the improvement of mitophagy and apoptosis in aging rats induced by D-galactose
title_short Diminazine protects against cardiac aging through the improvement of mitophagy and apoptosis in aging rats induced by D-galactose
title_sort diminazine protects against cardiac aging through the improvement of mitophagy and apoptosis in aging rats induced by d galactose
topic Aging
Apoptosis
Cardiac hypertrophy
Diminazine
Mitophagy
url https://doi.org/10.1186/s12872-025-04572-4
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