Role of beta1-adrenergic Blockade in Alleviation of Clozapine-induced Cardiotoxic effect in rats via modulation of cardiac cell death, macrophages, and gap junction intercellular communication proteins | ||
| SVU-International Journal of Medical Sciences | ||
| Volume 8, Issue 2, July 2025, Pages 270-288 PDF (1.73 M) | ||
| Document Type: Original research articles | ||
| DOI: 10.21608/svuijm.2025.403295.2213 | ||
| Authors | ||
| Hala M ElBadre1; Manal M Kamal* 2; Basel A Abdel-Wahab3; Safaa Yousef Salem3; Nashwa Ahmed Mohammed4; Noran M Ahmed5; Amr M Ahmed5; Reham I El-Mahdy6 | ||
| 1Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Assiut University, Assiut, Egypt | ||
| 2Department of Medical Physiology, Faculty of Medicine, Assiut University, Assiut, Egypt & Department of Physiology, College of Medicine, Qassim University, Buraidah, Saudi Arabia | ||
| 3Department of Medical Pharmacology, Faculty of Medicine, Assiut University, Assiut, Egypt | ||
| 4Department of Histology, Faculty of Medicine, Assiut University, Assiut, Egypt | ||
| 5Undergraduate Medical Student, Faculty of Medicine, Assiut University, Assiut, Egypt | ||
| 6Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Assiut University, Assiut, Egypt & Department of Basic medical science, Badr University, New Naser city, west of Assiut, Assiut, Egypt | ||
| Abstract | ||
| Background: Clozapine (CLZ) is an effective choice for the treatment of resistant schizophrenia; however, there is a risk of clozapine-induced cardiotoxicity. Connexin-43 (CX43) and Vimentin are intracellular structural-functional proteins involved in cardiac pathophysiology. Objectives: The current investigation aimed to assess the cardioprotective mechanisms of beta1-adrenergic blockade by atenolol (ATN) against clozapine (CLZ) induced cardiotoxicity, focusing on the implications for gap junction and intermediate filament proteins. Materials and methods: Thirty-two male rats were divided into four equal groups: control, clozapine-induced myocarditis (dose 25 mg/kg/day) i.p., myocarditis, and treated with oral ATN with dosage of 5 and 10 mg/kg), for 3 weeks. Biomarkers of cardiac injury, oxidative stress, inflammation (IL1β & TNFα), apoptosis, the levels of vimentin & CX43 expression & CD86 were determined via chemical, ELISA, RT-PCR, histopathological, and immunohistochemical investigations. Results: Clozapine-treated rats exhibited increased cardiac injury biomarkers, cardiac oxidative stress indices (NO and TBARS), proinflammatory cytokines, and increased expression of caspase-3, vimentin, CX43, and CD86, along with suppression of antioxidants (GSH and GSH-Px). Atenolol showed dose-dependent suppression of the biochemical and histopathological disturbances related to clozapine-induced cardiotoxicity and significant downregulation the expression of vimentin and CX43. Conclusion:The cardioprotective novel role of ATN in clozapine-induced myocarditis is linked to its selective β1-adrenergic blockade and its ability to repair myocardial proteins vimentin & CX43 by reversing the inflammatory response, oxidative damage, and cellular apoptosis. | ||
| Keywords | ||
| Atenolol; Cardioprotective; Clozapine; Intermediate filament proteins; Macrophage | ||
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