Reconsidering the Role of Melatonin in Rheumatoid Arthritis

MacDonald, Iona; Huang, Chien-Chung; Liu, Shan‐Chi; Tang, Chih‐Hsin

doi:10.3390/ijms21082877

Cited by 37 publications

(33 citation statements)

References 55 publications

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“…The levels of tissue lipid peroxidation and reduced glutathione were also brought back to that seen in control animals by continued melatonin treatment [45]. Melatonin, by suppressing the activity of M1 subtype macrophages, reduced inflammation [72] even evoked by autoimmunity [75]. It appears that ISO-induced oxidative stress and inflammation were suppressed by treatment with melatonin and omega-3 as both exert powerful anti-oxidants and anti-inflammatory properties [67,74].…”

Section: Discussionmentioning

confidence: 86%

Antiarrhythmic Effects of Melatonin and Omega-3 Are Linked with Protection of Myocardial Cx43 Topology and Suppression of Fibrosis in Catecholamine Stressed Normotensive and Hypertensive Rats

et al. 2020

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Cardiac β-adrenergic overstimulation results in oxidative stress, hypertrophy, ischemia, lesion, and fibrosis rendering the heart vulnerable to malignant arrhythmias. We aimed to explore the anti-arrhythmic efficacy of the anti-oxidative and anti-inflammatory compounds, melatonin, and omega-3, and their mechanisms of actions in normotensive and hypertensive rats exposed to isoproterenol (ISO) induced β-adrenergic overdrive. Eight-month-old, male SHR, and Wistar rats were injected during 7 days with ISO (cumulative dose, 118 mg/kg). ISO rats were either untreated or concomitantly treated with melatonin (10 mg/kg/day) or omega-3 (Omacor, 1.68 g/kg/day) until 60 days of ISO withdrawal and compared to non-ISO controls. Findings showed that both melatonin and omega-3 increased threshold current to induce ventricular fibrillation (VF) in ISO rats regardless of the strain. Prolonged treatment with these compounds resulted in significant suppression of ISO-induced extracellular matrix alterations, as indicated by reduced areas of diffuse fibrosis and decline of hydroxyproline, collagen-1, SMAD2/3, and TGF-β1 protein levels. Importantly, the highly pro-arrhythmic ISO-induced disordered cardiomyocyte distribution of electrical coupling protein, connexin-43 (Cx43), and its remodeling (lateralization) were significantly attenuated by melatonin and omega-3 in Wistar as well as SHR hearts. In parallel, both compounds prevented the post-ISO-related increase in Cx43 variant phosphorylated at serine 368 along with PKCε, which are known to modulate Cx43 remodeling. Melatonin and omega-3 increased SOD1 or SOD2 protein levels in ISO-exposed rats of both strains. Altogether, the results indicate that anti-arrhythmic effects of melatonin and omega-3 might be attributed to the protection of myocardial Cx43 topology and suppression of fibrosis in the setting of oxidative stress induced by catecholamine overdrive in normotensive and hypertensive rats.

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Section: Discussionmentioning

confidence: 86%

Antiarrhythmic Effects of Melatonin and Omega-3 Are Linked with Protection of Myocardial Cx43 Topology and Suppression of Fibrosis in Catecholamine Stressed Normotensive and Hypertensive Rats

et al. 2020

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“…Melatonin is one of the major neuroendocrine hormones that show a remarkable functional versatility. Indeed, although its primary function consists of the regulation of circadian rhythm, melatonin also promotes mitochondrial homeostasis, proliferation, apoptosis, metastasis, oncostatic, anti-aging, antioxidant, and immunomodulatory properties [ 62 , 63 , 83 ].…”

Section: Tryptophan Metabolism and Ramentioning

confidence: 99%

“…Therefore, on one hand, several researches suggest that melatonin may enhance pro-inflammatory activities and promote disease activity in RA, while, on the other, other preclinical and clinical investigations document substantial anti-inflammatory and immunoregulatory properties of melatonin in the same disease [ 83 ]. Some investigators have suggested that melatonin could be effective as adjunctive therapy in the treatment of RA [ 96 ].…”

Section: Tryptophan Metabolism and Ramentioning

confidence: 99%

Amino Acid Metabolism in Rheumatoid Arthritis: Friend or Foe?

et al. 2020

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In mammals, amino acid metabolism has evolved to act as a critical regulator of innate and adaptive immune responses. Rheumatoid arthritis (RA) is the most common form of inflammatory arthropathy sustained by autoimmune responses. We examine here the current knowledge of tryptophan and arginine metabolisms and the main immunoregulatory pathways in amino acid catabolism, in both RA patients and experimental models of arthritis. We found that l-tryptophan (Trp) metabolism and, in particular, the kynurenine pathway would exert protective effects in all experimental models and in some, but not all, RA patients, possibly due to single nucleotide polymorphisms in the gene coding for indoleamine 2,3-dioxygenase 1 (IDO1; the enzyme catalyzing the rate-limiting step of the kynurenine pathway). The function, i.e., either protective or pathogenetic, of the l-arginine (Arg) metabolism in RA was less clear. In fact, although immunoregulatory arginase 1 (ARG1) was highly induced at the synovial level in RA patients, its true functional role is still unknown, possibly because of few available preclinical data. Therefore, our analysis would indicate that amino acid metabolism represents a fruitful area of research for new drug targets for a more effective and safe therapy of RA and that further studies are demanding to pursue such an important objective.

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“…Although the reports regarding effects of melatonin on autoimmune inflammation are not consistent, its potential beneficial effects in this condition have drawn a great attention recently. For example, recent evidence has demonstrated that melatonin down-regulates MMP9 activity, as well as IL-1β and TNF-α expressions in the synovial fibroblasts of patients with rheumatoid arthritis (RA) (167). Melatonin also stimulates microRNA (miR-3150a-3p) to produce anti-apoptotic action in RA patients (167,168).…”

Section: Melatonin In Chronic Autoimmune Disease-induced Cardiovasculmentioning

confidence: 99%

“…For example, recent evidence has demonstrated that melatonin down-regulates MMP9 activity, as well as IL-1β and TNF-α expressions in the synovial fibroblasts of patients with rheumatoid arthritis (RA) (167). Melatonin also stimulates microRNA (miR-3150a-3p) to produce anti-apoptotic action in RA patients (167,168). Both systemic lupus erythematosus (SLE) and systemic sclerosis (SS) kindle pro-inflammatory responses leading to atherogenesis and myocardial infarction (79,80), which can be targeted by melatonin (152,153,155).…”

Section: Melatonin In Chronic Autoimmune Disease-induced Cardiovasculmentioning

confidence: 99%

Multiple strategies of melatonin protecting against cardiovascular injury related to inflammation: A comprehensive overview

Sarkar¹,

Chattopadhyay²,

Bandyopadhyay³

2021

Melatonin Res.

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The onset and progression of baneful chronic diseases are often accompanied by a torrent of uncontrolled inflammatory reactions. Although inflammation is a natural response to detect, eliminate, and counterpoise the harmful insults to physiological integrity, a persistent inflammation causes tissue damage or more serious disorders, for example, the atherosclerosis and myocardial infarction. Inflammation often occurs in the cardiovascular system, but are also caused by other disorders including metabolic syndrome, autoimmune diseases, AIDS, and cancer that can affect the cardiac health. To effectively treat heart diseases a potent remedy is necessary which not only suppresses the inflammation but also prevents inflammation-associated cardio-pathogenesis. The ubiquitous antioxidant molecule melatonin has both anti-inflammatory and cardioprotective activities. Melatonin executes its anti-inflammatory activity by its antioxidant function or by targeting multiple intracellular signalling cascades such as modulating cytokine profile, blocking inflammasome activation and apoptosis. Lipid dysregulation and endothelial dysfunction that play a crucial role in the pathogenesis of atherosclerosis, insulin resistance, and diabetes are prevented by melatonin. Attenuation of mitochondrial and ER stress by melatonin is also pertinent to its cardioprotective action. Additionally, melatonin by its immuno-stimulatory activity can suppress inflammaging and immuno-senescence in HIV patients and thereby averts chronic inflammation-induced cardiovascular abnormality in these subjects. Modulation of cytokine profile and decrease in MMP-9 secretion by melatonin is beneficial in autoimmune conditions. In addition to its anti-tumour potency, melatonin can reduce chemotherapy-induced cardio-toxicity in cancer patients. This review, therefore, provides a concise summary of the currently available information appertaining to the roles of melatonin in mitigation of chronic inflammation and its effect on cardiovascular integrity.

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Reconsidering the Role of Melatonin in Rheumatoid Arthritis

Cited by 37 publications

References 55 publications

Antiarrhythmic Effects of Melatonin and Omega-3 Are Linked with Protection of Myocardial Cx43 Topology and Suppression of Fibrosis in Catecholamine Stressed Normotensive and Hypertensive Rats

Antiarrhythmic Effects of Melatonin and Omega-3 Are Linked with Protection of Myocardial Cx43 Topology and Suppression of Fibrosis in Catecholamine Stressed Normotensive and Hypertensive Rats

Amino Acid Metabolism in Rheumatoid Arthritis: Friend or Foe?

Multiple strategies of melatonin protecting against cardiovascular injury related to inflammation: A comprehensive overview

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