An integrated strategy to explore the potential role of melatonin against copper-induced adrenaline toxicity in rat cardiomyocytes: Insights into oxidative stress, inflammation, and apoptosis.
Int Immunopharmacol
; 120: 110301, 2023 Jul.
Article
em En
| MEDLINE
| ID: mdl-37224648
ABSTRACT
AIMS:
Circumstantial anxiety as well as chronic stress may stimulate the release of stress hormones including catecholamines. Adrenaline toxicity has been implicated in many cardiovascular conditions. Considering previous literature that suggests the oxidative potential of the adrenaline-copper entity, we have investigated its potential nocuous role in isolated adult rat cardiomyocytes, the underlying molecular mechanism, and its possible protection by melatonin. MAINMETHODS:
Given the mechanistic congruity of adrenaline-copper (AC) with the well-established H2O2-copper-ascorbate (HCA) system of free radical generation, we have used the latter as a representative model to study the cytotoxic nature of AC. We further investigated the cardioprotective efficacy of melatonin in both the stress models through scanning electron microscopy, immunofluorescence, flow cytometry, and western blot analysis. KEYFINDINGS:
Results show that melatonin significantly protects AC-treated cardiomyocytes from ROS-mediated membrane damage, disruption of mitochondrial membrane potential, antioxidant imbalance, and distortion of cellular morphology. Melatonin protects cardiomyocytes from inflammation by downregulating pro-inflammatory mediators viz., COX-2, NF-κB, TNF-α, and upregulating anti-inflammatory IL-10. Melatonin significantly ameliorated cardiomyocyte apoptosis in AC and HCA-treated cells as evidenced by decreased BAX/BCL-2 ratio and subsequent suppression of caspase-9 and caspase-3 levels. The isothermal calorimetric study revealed that melatonin inhibits the binding of adrenaline bitartrate with copper in solution, which fairly explains the rescue potential of melatonin against AC-mediated toxicity in cardiomyocytes.SIGNIFICANCE:
Findings suggest that the multipronged strategy of melatonin that includes its antioxidant, anti-inflammatory, anti-apoptotic, and overall cardioprotective ability may substantiate its potential therapeutic efficacy against adrenaline-copper-induced damage and death of adult rat cardiomyocytes.Palavras-chave
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Base de dados:
MEDLINE
Assunto principal:
Melatonina
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article