The Prophylactic Role of Amlodipine in Cerebral Ischemia via PGC1 α/Nrf2/TFAM Pathway Activation
El-Harty, Y., El-Gohary, R., Ghabrial, M., El-Harty, S., Elkordy, A., Hegab, I., El Tabaa, M. (2025). The Prophylactic Role of Amlodipine in Cerebral Ischemia via PGC1 α/Nrf2/TFAM Pathway Activation. EKB Journal Management System, 45(2), 206-218. doi: 10.21608/besps.2024.328491.1182
Yasmeen M. El-Harty; Rehab M. El-Gohary; Maram mofreh Mahrous Ghabrial; Sameh M. El-Harty; Alaa Elkordy; Islam Ibrahim Hegab; Maram Mohammed El Tabaa. "The Prophylactic Role of Amlodipine in Cerebral Ischemia via PGC1 α/Nrf2/TFAM Pathway Activation". EKB Journal Management System, 45, 2, 2025, 206-218. doi: 10.21608/besps.2024.328491.1182
El-Harty, Y., El-Gohary, R., Ghabrial, M., El-Harty, S., Elkordy, A., Hegab, I., El Tabaa, M. (2025). 'The Prophylactic Role of Amlodipine in Cerebral Ischemia via PGC1 α/Nrf2/TFAM Pathway Activation', EKB Journal Management System, 45(2), pp. 206-218. doi: 10.21608/besps.2024.328491.1182
El-Harty, Y., El-Gohary, R., Ghabrial, M., El-Harty, S., Elkordy, A., Hegab, I., El Tabaa, M. The Prophylactic Role of Amlodipine in Cerebral Ischemia via PGC1 α/Nrf2/TFAM Pathway Activation. EKB Journal Management System, 2025; 45(2): 206-218. doi: 10.21608/besps.2024.328491.1182

The Prophylactic Role of Amlodipine in Cerebral Ischemia via PGC1 α/Nrf2/TFAM Pathway Activation

Bulletin of Egyptian Society for Physiological Sciences
Volume 45, Issue 2, April 2025, Page 206-218  XML PDF (736.87 K)
Document Type: Original Article
DOI: 10.21608/besps.2024.328491.1182
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Authors
Yasmeen M. El-Harty email orcid 1; Rehab M. El-Gohary2; Maram mofreh Mahrous Ghabrial3; Sameh M. El-Harty4; Alaa Elkordy5; Islam Ibrahim Hegaborcid 6; Maram Mohammed El Tabaaorcid 7
1Medical physiology department, Faculty of Medicine, Tanta University
2Department of Medical Biochemistry, Faculty of Medicine, Tanta University, Tanta 31527, Egypt
3Lecturer of anatomy and embryology, Faculty of Medicine, Tanta University,
4Department of Cardiovascular Medicine, Faculty of Medicine, Tanta University, Tanta 31527, Egypt
5Neuropsychiatry department, Faculty of Medicine,Tanta University,Tanta,Egypt
6Department of Medical Physiology, Faculty of Medicine, Tanta University, Tanta 31527, Egypt Department of Bio-Physiology, Ibn Sina National College for Medical Studies, Jeddah, Saudi Arabia
7Medical Physiology, Faculty of Medicine, Tanta University
Abstract
Ischemic stroke is a leading cause of permanent disability and death. Mitochondrial dynamics is a novel target strategy for management of cerebral ischemia. Amlodipine was recently reported to target mitochondria in renal ischemia suggesting it as a possible mechanism in cerebral ischemia. 30 adult male rats were divided into 3 groups: 1-Sham-operated group: with no ischemia, received normal saline. 2-Ischemic Group: with Middle Cerebral Artery Occlusion (MCAO) model & 3-Amlodipine group: received Amlodipine (10 mg/kg) via gavage twice, 10 minutes before and 24 hours after developing MCAO model 72 hours after MCAO, rotarod test was performed. At the end of the experiment, serum oxidative DNA damage marker (8-hydroxy-2’-deoxyguanosine level) was assayed. Additionally, oxidative stress markers (Reactive Oxygen Species, malondialdehyde and superoxide dismutase), inflammatory marker (tumor necrosis factor-alpha), mitochondrial (Peroxisome proliferator-activated receptor gamma coactivator (PGC1α), Mitochondrial transcription factor A (TFAM)) levels were measured in brain tissue as well as the gene expression of nuclear factor erythroid 2-related factor 2 (NRF2). Histopathological and caspase-3 immunohistochemistry were also performed. Our results showed that amlodipine significantly protects against the ischemic brain injury as evident by the upregulation of the PGC1α/Nrf2/TFAM which restored normal mitochondrial function. Also, the ischemia-induced oxidative stress, inflammatory stress, oxidative DNA damage and apoptosis were mitigated by amlodipine with subsequent decrease of the neuronal damage. Accordingly, amlodipine use in protection against ischemic stroke is favored due to its mitochondrial targeting mechanism. Nonetheless, more research is needed to fully understand its additional effects.
Keywords
Amlodipine; Cerebral ischemia; PGC1α; Nrf2; TFAM
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