Protective Effects of 2-Methoxyestradiol on Acute Isoproterenol-Induced Cardiac Injury in Rats
Myocardial injury (MI) is an important pathological driver of mortality worldwide., and arises as a result of imbalances between myocardial oxygen demand and supply. In MI, oxidative stress often leads to inflammatory changes and apoptosis. Current therapies for MI are known to cause various adverse...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-10-01
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| Series: | Saudi Pharmaceutical Journal |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S1319016423002827 |
| _version_ | 1797676265043394560 |
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| author | Rawan H. Hareeri Abdulrahman M. Alam Amina M. Bagher Abdulmohsin J. Alamoudi Mohammed M. Aldurdunji Rasheed A. Shaik Basma G. Eid Osama M. Ashour |
| author_facet | Rawan H. Hareeri Abdulrahman M. Alam Amina M. Bagher Abdulmohsin J. Alamoudi Mohammed M. Aldurdunji Rasheed A. Shaik Basma G. Eid Osama M. Ashour |
| author_sort | Rawan H. Hareeri |
| collection | DOAJ |
| description | Myocardial injury (MI) is an important pathological driver of mortality worldwide., and arises as a result of imbalances between myocardial oxygen demand and supply. In MI, oxidative stress often leads to inflammatory changes and apoptosis. Current therapies for MI are known to cause various adverse effects. Consequently, the development of new therapeutic agents with a reduced adverse event profile is necessary. In this regard, 2-methoxyestradiol (2ME), the metabolic end-product of oestradiol, possesses anti-inflammatory and antioxidant properties. The aim of this research is to assess the impact of 2ME on cardiac injury caused by isoproterenol (ISO) in rats. Animals were separated into six groups; controls, and those receiving 2ME (1 mg/kg), ISO (85 mg/kg), ISO + 2ME (0.25 mg/kg), ISO + 2ME (0.5 mg/kg), and ISO + 2ME (1 mg/kg). 2ME significantly attenuated ISO-induced changes in electrocardiographic changes and the cardiac histological pattern. This compound also decreased lactate dehydrogenase activity, creatine kinase myocardial band and troponin levels. The ability of 2ME to act as an antioxidant was shown by a decrease in malondialdehyde concentration, and the restoration of glutathione levels and superoxide dismutase activity. Additionally, 2ME antagonized inflammation and cardiac cell apoptosis, a process determined to be mediated, at least partially, by suppression of Gal-3/TLR4/MyD88/NF-κB signaling pathway. 2ME offers protection against acute ISO-induced MI in rats and offers a novel therapeutic management option. |
| first_indexed | 2024-03-11T22:26:29Z |
| format | Article |
| id | doaj.art-0beb8f15362141c69fc269e1ca464b55 |
| institution | Directory Open Access Journal |
| issn | 1319-0164 |
| language | English |
| last_indexed | 2024-03-11T22:26:29Z |
| publishDate | 2023-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Saudi Pharmaceutical Journal |
| spelling | doaj.art-0beb8f15362141c69fc269e1ca464b552023-09-24T05:14:23ZengElsevierSaudi Pharmaceutical Journal1319-01642023-10-013110101787Protective Effects of 2-Methoxyestradiol on Acute Isoproterenol-Induced Cardiac Injury in RatsRawan H. Hareeri0Abdulrahman M. Alam1Amina M. Bagher2Abdulmohsin J. Alamoudi3Mohammed M. Aldurdunji4Rasheed A. Shaik5Basma G. Eid6Osama M. Ashour7Department of Pharmacology and Toxicology, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia; Corresponding author at: Department of Pharmacology and Toxicology, King Abdulaziz University, Jeddah, Saudi Arabia.Department of Pharmacology and Toxicology, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi ArabiaDepartment of Pharmacology and Toxicology, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi ArabiaDepartment of Pharmacology and Toxicology, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi ArabiaDepartment of Clinical Pharmacy, College of Pharmacy, Umm Al-Qura University, Makkah, Saudi ArabiaDepartment of Pharmacology and Toxicology, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi ArabiaDepartment of Pharmacology and Toxicology, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi ArabiaDepartment of Pharmacology and Toxicology, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi ArabiaMyocardial injury (MI) is an important pathological driver of mortality worldwide., and arises as a result of imbalances between myocardial oxygen demand and supply. In MI, oxidative stress often leads to inflammatory changes and apoptosis. Current therapies for MI are known to cause various adverse effects. Consequently, the development of new therapeutic agents with a reduced adverse event profile is necessary. In this regard, 2-methoxyestradiol (2ME), the metabolic end-product of oestradiol, possesses anti-inflammatory and antioxidant properties. The aim of this research is to assess the impact of 2ME on cardiac injury caused by isoproterenol (ISO) in rats. Animals were separated into six groups; controls, and those receiving 2ME (1 mg/kg), ISO (85 mg/kg), ISO + 2ME (0.25 mg/kg), ISO + 2ME (0.5 mg/kg), and ISO + 2ME (1 mg/kg). 2ME significantly attenuated ISO-induced changes in electrocardiographic changes and the cardiac histological pattern. This compound also decreased lactate dehydrogenase activity, creatine kinase myocardial band and troponin levels. The ability of 2ME to act as an antioxidant was shown by a decrease in malondialdehyde concentration, and the restoration of glutathione levels and superoxide dismutase activity. Additionally, 2ME antagonized inflammation and cardiac cell apoptosis, a process determined to be mediated, at least partially, by suppression of Gal-3/TLR4/MyD88/NF-κB signaling pathway. 2ME offers protection against acute ISO-induced MI in rats and offers a novel therapeutic management option.http://www.sciencedirect.com/science/article/pii/S13190164230028272-Methoxyestradiol (2ME)Isoproterenol (ISO)Myocardial Injury (MI)Oxidative StressInflammation |
| spellingShingle | Rawan H. Hareeri Abdulrahman M. Alam Amina M. Bagher Abdulmohsin J. Alamoudi Mohammed M. Aldurdunji Rasheed A. Shaik Basma G. Eid Osama M. Ashour Protective Effects of 2-Methoxyestradiol on Acute Isoproterenol-Induced Cardiac Injury in Rats Saudi Pharmaceutical Journal 2-Methoxyestradiol (2ME) Isoproterenol (ISO) Myocardial Injury (MI) Oxidative Stress Inflammation |
| title | Protective Effects of 2-Methoxyestradiol on Acute Isoproterenol-Induced Cardiac Injury in Rats |
| title_full | Protective Effects of 2-Methoxyestradiol on Acute Isoproterenol-Induced Cardiac Injury in Rats |
| title_fullStr | Protective Effects of 2-Methoxyestradiol on Acute Isoproterenol-Induced Cardiac Injury in Rats |
| title_full_unstemmed | Protective Effects of 2-Methoxyestradiol on Acute Isoproterenol-Induced Cardiac Injury in Rats |
| title_short | Protective Effects of 2-Methoxyestradiol on Acute Isoproterenol-Induced Cardiac Injury in Rats |
| title_sort | protective effects of 2 methoxyestradiol on acute isoproterenol induced cardiac injury in rats |
| topic | 2-Methoxyestradiol (2ME) Isoproterenol (ISO) Myocardial Injury (MI) Oxidative Stress Inflammation |
| url | http://www.sciencedirect.com/science/article/pii/S1319016423002827 |
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