The potential therapeutic role of Lisinopril in augmenting the striatal neuroplasticity via the striatal ACE2/Ang1-7/MAS receptor axis in 3-nitropropionic acid-induced Huntington’s disease in rats: shifting paradigms in Huntington’s disease treatment

Abstract Background The exact pathogenesis of Huntington’s disease (HD) remains unclear. However, mitochondrial dysfunction and oxidative stress are supposed to play a significant role. The objective of this study was to examine the possible neuroprotective effect of Lisinopril (Lisino) in a 3-nitro...

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Main Authors: Hanaa Wanas, Mostafa Adel Rabie, Basma Emad Aboulhoda, Nagwa Mahmoud Ramadan, Sahar Abdelwahab, Sara Sayed Kadry Abdallah, Eid Nassar Ali, Leyan Nasruddeen Khayruddeen, Yasir Hassan Elhassan, Hadel Mahroos Alghabban, Shaimaa Mohamed Abdelsalam, Amira Karam Khalifa
Format: Article
Language:English
Published: SpringerOpen 2024-11-01
Series:Future Journal of Pharmaceutical Sciences
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Online Access:https://doi.org/10.1186/s43094-024-00724-z
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author Hanaa Wanas
Mostafa Adel Rabie
Basma Emad Aboulhoda
Nagwa Mahmoud Ramadan
Sahar Abdelwahab
Sara Sayed Kadry Abdallah
Eid Nassar Ali
Leyan Nasruddeen Khayruddeen
Yasir Hassan Elhassan
Hadel Mahroos Alghabban
Shaimaa Mohamed Abdelsalam
Amira Karam Khalifa
author_facet Hanaa Wanas
Mostafa Adel Rabie
Basma Emad Aboulhoda
Nagwa Mahmoud Ramadan
Sahar Abdelwahab
Sara Sayed Kadry Abdallah
Eid Nassar Ali
Leyan Nasruddeen Khayruddeen
Yasir Hassan Elhassan
Hadel Mahroos Alghabban
Shaimaa Mohamed Abdelsalam
Amira Karam Khalifa
author_sort Hanaa Wanas
collection DOAJ
description Abstract Background The exact pathogenesis of Huntington’s disease (HD) remains unclear. However, mitochondrial dysfunction and oxidative stress are supposed to play a significant role. The objective of this study was to examine the possible neuroprotective effect of Lisinopril (Lisino) in a 3-nitropropionic acid-produced HD in rats. Methods Sixty-four rats were divided into four groups (16/group): Group (1): Normal control group, Group (2): Lisinopril control group, Group (3): 3-NP non-treated group, and Group (4): (3-NP + Lisinopril) group. Behavior assessments (open field test, rotarod test, grip strength test) were performed along with different histological and biochemical parameters. Results Lisinopril upregulated the expression of the ACE2/Ang1-7/MAS receptor (MasR) axis of RAS, which triggered the PI3K/Akt pathway and prompted the CREB/BDNF neurogenesis signal. Furthermore, Lisinopril remarkably downregulated the inflammatory cytokines (NF-κB, TNF-α, IFN-γ and IL-6), decreased apoptotic markers (p53, BAX/Bcl2 ratio, Cyt-c and caspase-3) and upgraded the mitochondrial TFAM content and SDH activity along with restoration of the redox mechanism by recovering SOD, catalase, GSH and Nrf2. Conclusion Notably, the outcomes of this study disclosed that Lisinopril could be a future neuroprotective therapeutic candidate against HD.
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spelling doaj-art-6f44e7a5b7074e54bd780b4c933652d22024-11-10T12:11:50ZengSpringerOpenFuture Journal of Pharmaceutical Sciences2314-72532024-11-0110112210.1186/s43094-024-00724-zThe potential therapeutic role of Lisinopril in augmenting the striatal neuroplasticity via the striatal ACE2/Ang1-7/MAS receptor axis in 3-nitropropionic acid-induced Huntington’s disease in rats: shifting paradigms in Huntington’s disease treatmentHanaa Wanas0Mostafa Adel Rabie1Basma Emad Aboulhoda2Nagwa Mahmoud Ramadan3Sahar Abdelwahab4Sara Sayed Kadry Abdallah5Eid Nassar Ali6Leyan Nasruddeen Khayruddeen7Yasir Hassan Elhassan8Hadel Mahroos Alghabban9Shaimaa Mohamed Abdelsalam10Amira Karam Khalifa11Department of Medical Pharmacology, Faculty of Medicine, Cairo UniversityDepartment of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo UniversityDepartment of Medical Anatomy and Embryology, Faculty of Medicine, Cairo UniversityDepartment of Medical Physiology, Faculty of Medicine, Cairo UniversityDepartment of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Cairo UniversityDepartment of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Cairo UniversityDepartment of Medical Anatomy and Embryology, Faculty of Medicine, Cairo UniversityDepartment of Basic Medical Science, College of Medicine, Taibah UniversityDepartment of Basic Medical Science, College of Medicine, Taibah UniversityDepartment of Basic Medical Science, College of Medicine, Taibah UniversityDepartment of Anatomic Pathology, Faculty of Medicine, Cairo UniversityDepartment of Medical Pharmacology, Faculty of Medicine, Cairo UniversityAbstract Background The exact pathogenesis of Huntington’s disease (HD) remains unclear. However, mitochondrial dysfunction and oxidative stress are supposed to play a significant role. The objective of this study was to examine the possible neuroprotective effect of Lisinopril (Lisino) in a 3-nitropropionic acid-produced HD in rats. Methods Sixty-four rats were divided into four groups (16/group): Group (1): Normal control group, Group (2): Lisinopril control group, Group (3): 3-NP non-treated group, and Group (4): (3-NP + Lisinopril) group. Behavior assessments (open field test, rotarod test, grip strength test) were performed along with different histological and biochemical parameters. Results Lisinopril upregulated the expression of the ACE2/Ang1-7/MAS receptor (MasR) axis of RAS, which triggered the PI3K/Akt pathway and prompted the CREB/BDNF neurogenesis signal. Furthermore, Lisinopril remarkably downregulated the inflammatory cytokines (NF-κB, TNF-α, IFN-γ and IL-6), decreased apoptotic markers (p53, BAX/Bcl2 ratio, Cyt-c and caspase-3) and upgraded the mitochondrial TFAM content and SDH activity along with restoration of the redox mechanism by recovering SOD, catalase, GSH and Nrf2. Conclusion Notably, the outcomes of this study disclosed that Lisinopril could be a future neuroprotective therapeutic candidate against HD.https://doi.org/10.1186/s43094-024-00724-zHuntington’s diseaseRenin–angiotensin systemLisinoprilMitochondrial dysfunction3-nitropropionic acid
spellingShingle Hanaa Wanas
Mostafa Adel Rabie
Basma Emad Aboulhoda
Nagwa Mahmoud Ramadan
Sahar Abdelwahab
Sara Sayed Kadry Abdallah
Eid Nassar Ali
Leyan Nasruddeen Khayruddeen
Yasir Hassan Elhassan
Hadel Mahroos Alghabban
Shaimaa Mohamed Abdelsalam
Amira Karam Khalifa
The potential therapeutic role of Lisinopril in augmenting the striatal neuroplasticity via the striatal ACE2/Ang1-7/MAS receptor axis in 3-nitropropionic acid-induced Huntington’s disease in rats: shifting paradigms in Huntington’s disease treatment
Future Journal of Pharmaceutical Sciences
Huntington’s disease
Renin–angiotensin system
Lisinopril
Mitochondrial dysfunction
3-nitropropionic acid
title The potential therapeutic role of Lisinopril in augmenting the striatal neuroplasticity via the striatal ACE2/Ang1-7/MAS receptor axis in 3-nitropropionic acid-induced Huntington’s disease in rats: shifting paradigms in Huntington’s disease treatment
title_full The potential therapeutic role of Lisinopril in augmenting the striatal neuroplasticity via the striatal ACE2/Ang1-7/MAS receptor axis in 3-nitropropionic acid-induced Huntington’s disease in rats: shifting paradigms in Huntington’s disease treatment
title_fullStr The potential therapeutic role of Lisinopril in augmenting the striatal neuroplasticity via the striatal ACE2/Ang1-7/MAS receptor axis in 3-nitropropionic acid-induced Huntington’s disease in rats: shifting paradigms in Huntington’s disease treatment
title_full_unstemmed The potential therapeutic role of Lisinopril in augmenting the striatal neuroplasticity via the striatal ACE2/Ang1-7/MAS receptor axis in 3-nitropropionic acid-induced Huntington’s disease in rats: shifting paradigms in Huntington’s disease treatment
title_short The potential therapeutic role of Lisinopril in augmenting the striatal neuroplasticity via the striatal ACE2/Ang1-7/MAS receptor axis in 3-nitropropionic acid-induced Huntington’s disease in rats: shifting paradigms in Huntington’s disease treatment
title_sort potential therapeutic role of lisinopril in augmenting the striatal neuroplasticity via the striatal ace2 ang1 7 mas receptor axis in 3 nitropropionic acid induced huntington s disease in rats shifting paradigms in huntington s disease treatment
topic Huntington’s disease
Renin–angiotensin system
Lisinopril
Mitochondrial dysfunction
3-nitropropionic acid
url https://doi.org/10.1186/s43094-024-00724-z
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