RESUMO
Lethal ventricular arrhythmias increase in patients with chronic kidney disease that suffer an acute coronary event. Chronic kidney disease induces myocardial remodeling, oxidative stress, and arrhythmogenesis. A manifestation of the relationship between kidney and heart is the concomitant reduction in vitamin D receptor (VDR) and the increase in angiotensin II receptor type 1 (AT1 ). Melatonin has renal and cardiac protective actions. One potential mechanism is the increase in the heat shock protein 70 (Hsp70)-an antioxidant factor. We aim to determine the mechanisms involved in melatonin (Mel) prevention of kidney damage and arrhythmogenic heart remodeling. Unilateral ureteral-obstruction (UUO) and sham-operated rats were treated with either melatonin (4 mg/kg/day) or vehicle for 15 days. Hearts and kidneys from obstructed rats showed a reduction in VDR and Hsp70. Associated with AT1 up-regulation in the kidneys and the heart of UUO rats also increased oxidative stress, fibrosis, apoptosis, mitochondrial edema, and dilated crests. Melatonin prevented these changes and ventricular fibrillation during reperfusion. The action potential lengthened and hyperpolarized in melatonin-treated rats throughout the experiment. We conclude that melatonin prevents renal damage and arrhythmogenic myocardial remodeling during unilateral ureteral obstruction due to a decrease in oxidative stress/fibrosis/apoptosis associated with AT1 reduction and Hsp70-VDR increase.
Assuntos
Proteínas de Choque Térmico HSP70/metabolismo , Melatonina/uso terapêutico , Receptor Tipo 1 de Angiotensina/metabolismo , Receptores de Calcitriol/metabolismo , Taquicardia Ventricular/tratamento farmacológico , Taquicardia Ventricular/metabolismo , Actinas/metabolismo , Animais , Apoptose/efeitos dos fármacos , Fibrose/metabolismo , Proteínas de Choque Térmico HSP70/genética , Marcação In Situ das Extremidades Cortadas , Técnicas In Vitro , Rim/metabolismo , Masculino , Microscopia Eletrônica , Microscopia de Fluorescência , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Miocárdio/metabolismo , NADPH Oxidases/metabolismo , Ratos , Ratos Endogâmicos WKY , Receptor Tipo 1 de Angiotensina/genética , Receptores de Calcitriol/genéticaRESUMO
Hydroxytyrosol (HT) ((3,4-Dihydroxyphenyl)ethanol) is a polyphenol mainly present in extra virgin olive oil (EVOO) but also in red wine. It has a potent antioxidant effect related to hydrogen donation, and the ability to improve radical stability. The phenolic content of olive oil varies between 100 and 600 mg/kg, due to multiple factors (place of cultivation, climate, variety of the olive and level of ripening at the time of harvest), with HT and its derivatives providing half of that content. When consumed, EVOO's phenolic compounds are hydrolyzed in the stomach and intestine, increasing levels of free HT which is then absorbed in the small intestine, forming phase II metabolites. It has been demonstrated that HT consumption is safe even at high doses, and that is not genotoxic or mutagenic in vitro. The beneficial effects of HT have been studied in humans, as well as cellular and animal models, mostly in relation to consumption of EVOO. Many properties, besides its antioxidant capacity, have been attributed to this polyphenol. The aim of this review was to assess the main properties of HT for human health with emphasis on those related to the possible prevention and/or treatment of non-communicable diseases.
Assuntos
Citoproteção/efeitos dos fármacos , Álcool Feniletílico/análogos & derivados , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacologia , Antioxidantes/química , Antioxidantes/farmacologia , Autofagia/efeitos dos fármacos , Humanos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Azeite de Oliva/química , Estresse Oxidativo/efeitos dos fármacos , Álcool Feniletílico/química , Álcool Feniletílico/farmacologiaRESUMO
Neopterin, a byproduct of the tetrahydrobiopterin de novo pathway, is found in increased levels in cerebrospinal fluid and plasma and significantly increases upon damage, infection or during immune system activation. The production of this compound seems almost restricted to the monocyte/macrophage linage cells, in response to interferon-γ stimulation. However, it is unclear whether and which nervous cells are able to synthesize neopterin, respond to any stressor applied extracellularly, or even the role of the compound in the central nervous system. Here we propose a potential cytoprotective role of neopterin in the brain, and show evidence that cultured rat astrocytes are responsive to the molecule; the pterin elicited increased hemeoxygenase-1 cellular content and decreased oxidative stress induced by mitochondrial dysfunction. Further studies are needed to clarify neopterin's cytoprotective effects in the central nervous system, and its potential role in different neuroinflammatory diseases.