Role of cardiac β1-adrenergic and A1-adenosine receptors in severe arrhythmias related to Parkinson's disease

Rodrigues, Francisco Sandro Menezes; Pires-Oliveira, Marcelo; Araújo, Evaldo Stanislau Affonso de; Ferraz, Henrique Ballalai; Finsterer, Josef; Olszewer, Efrain; Taha, Murched Omar; Scorza, Carla A.; Caricati‐Neto, Afonso; Scorza, Fúlvio A.

doi:10.1016/j.clinsp.2023.100243

Cited by 2 publications

(1 citation statement)

References 55 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…To replicate an animal model of AMI in the lab, rats underwent surgical procedures following the protocol that our research group had previously published [ 13 , 14 ]. To induce unconsciousness, the rats were initially given intraperitoneal injections of xylazine (10 mg/kg), ketamine (100 mg/kg), and tramadol (2 mg/kg).…”

Section: Methodsmentioning

confidence: 99%

Cardiotoxic Effects Produced by Omeprazole and Methylene Blue in an Animal Model of Cardiac Ischemia and Reperfusion and Potential Implications for the Pharmacological Strategy for Vasoplegic Syndrome

de Araújo,

Tallo,

Oliveira

et al. 2024

Biomedicines

Self Cite

View full text Add to dashboard Cite

Defined as systemic hypotension caused by intense vasodilation due to the loss of systemic vascular resistance, vasoplegic syndrome (VS) is associated with elevated morbidity and mortality in humans. Although vasopressors such as norepinephrine and vasopressin are the first-choice drugs for VS treatment, several other drugs such as methylene blue (MB) can be used as adjuvant therapy including rescue therapy. To develop new pharmacological strategies to reduce the risk of VS, we investigated the effects of treatments with MB (2 mg/kg/IV), omeprazole (OME, 10 mg/kg/IV), and their combination in an animal model of cardiac ischemia–reperfusion (CIR). The ventricular arrhythmia (VA), atrioventricular block (AVB), and lethality (LET) incidence rates caused by CIR (evaluated via ECG) and serum levels of the cardiac lesion biomarkers creatine kinase–MB (CK-MB) and troponin I (TnI) in adult rats pretreated with saline solution 0.9% and submitted to CIR (SS + CIR group) were compared to those pretreated with MB (MB + CIR group), OME (OME + CIR group), or the MB + OME combination (MB + OME + CIR group). The AVB and LET incidence rates in the MB + CIR (100%), OME + CIR (100%), and MB + OME + CIR (100%) groups were significantly higher compared to the SS + CIR group (60%). The serum level of CK-MB in these groups were also significantly higher compared to the SS + CIR group, demonstrating that the treatments before CIR with MB, OME, and MB + OME produced similar effects in relation to cardiac function and the occurrence of lesions. These results demonstrate that the treatment of animals subjected to the CIR protocol with OME produced the same effects promoted by the treatment with MB, which may suggest the possibility of using OME alone or in combination with MB in medical clinics in treatment of VS.

show abstract

Section: Methodsmentioning

confidence: 99%

Cardiotoxic Effects Produced by Omeprazole and Methylene Blue in an Animal Model of Cardiac Ischemia and Reperfusion and Potential Implications for the Pharmacological Strategy for Vasoplegic Syndrome

de Araújo,

Tallo,

Oliveira

et al. 2024

Biomedicines

Self Cite

View full text Add to dashboard Cite

show abstract

Synergistic integration of deep learning with protein docking in cardiovascular disease treatment strategies

Yakoubi

2024

IUBMB Life

View full text Add to dashboard Cite

This research delves into the exploration of the potential of tocopherol‐based nanoemulsion as a therapeutic agent for cardiovascular diseases (CVD) through an in‐depth molecular docking analysis. The study focuses on elucidating the molecular interactions between tocopherol and seven key proteins (1O8a, 4YAY, 4DLI, 1HW9, 2YCW, 1BO9 and 1CX2) that play pivotal roles in CVD development. Through rigorous in silico docking investigations, assessment was conducted on the binding affinities, inhibitory potentials and interaction patterns of tocopherol with these target proteins. The findings revealed significant interactions, particularly with 4YAY, displaying a robust binding energy of −6.39 kcal/mol and a promising Ki value of 20.84 μM. Notable interactions were also observed with 1HW9, 4DLI, 2YCW and 1CX2, further indicating tocopherol's potential therapeutic relevance. In contrast, no interaction was observed with 1BO9. Furthermore, an examination of the common residues of 4YAY bound to tocopherol was carried out, highlighting key intermolecular hydrophobic bonds that contribute to the interaction's stability. Tocopherol complies with pharmacokinetics (Lipinski's and Veber's) rules for oral bioavailability and proves safety non‐toxic and non‐carcinogenic. Thus, deep learning‐based protein language models ESM1‐b and ProtT5 were leveraged for input encodings to predict interaction sites between the 4YAY protein and tocopherol. Hence, highly accurate predictions of these critical protein–ligand interactions were achieved. This study not only advances the understanding of these interactions but also highlights deep learning's immense potential in molecular biology and drug discovery. It underscores tocopherol's promise as a cardiovascular disease management candidate, shedding light on its molecular interactions and compatibility with biomolecule‐like characteristics.

show abstract

Role of cardiac β1-adrenergic and A1-adenosine receptors in severe arrhythmias related to Parkinson's disease

Cited by 2 publications

References 55 publications

Cardiotoxic Effects Produced by Omeprazole and Methylene Blue in an Animal Model of Cardiac Ischemia and Reperfusion and Potential Implications for the Pharmacological Strategy for Vasoplegic Syndrome

Cardiotoxic Effects Produced by Omeprazole and Methylene Blue in an Animal Model of Cardiac Ischemia and Reperfusion and Potential Implications for the Pharmacological Strategy for Vasoplegic Syndrome

Synergistic integration of deep learning with protein docking in cardiovascular disease treatment strategies

Contact Info

Product

Resources

About