Melatonin: Antioxidant and modulatory properties in age‐related changes during Trypanosoma cruzi infection

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126

Melatonin is a ubiquitous hormone found in various organisms and highly affects the function of immune cells. In this review, we summarize the current understanding of the significance of melatonin in macrophage biology and the beneficial effects of melatonin in macrophage‐associated diseases. Enzymes associated with synthesis of melatonin, as well as membrane receptors for melatonin, are found in macrophages. Indeed, melatonin influences the phenotype polarization of macrophages. Mechanistically, the roles of melatonin in macrophages are related to several cellular signaling pathways, such as NF‐κB, STATs, and NLRP3/caspase‐1. Notably, miRNAs (eg, miR‐155/‐34a/‐23a), cellular metabolic pathways (eg, α‐KG, HIF‐1α, and ROS), and mitochondrial dynamics and mitophagy are also involved. Thus, melatonin modulates the development and progression of various macrophage‐associated diseases, such as cancer and rheumatoid arthritis. This review provides a better understanding about the importance of melatonin in macrophage biology and macrophage‐associated diseases.

Section: Macrophage-associated Diseasesmentioning

confidence: 60%

“…Moreover, numbers of peritoneal macrophages were decreased, however, to levels much below those of uninfected controls . The protective role of melatonin is not restricted to macrophages, but has also to be seen in the context of effects on other immune cells, such as T lymphocytes and thymocytes …”

Section: Melatonin In Macrophage‐associated Diseasesmentioning

confidence: 98%

Melatonin in macrophage biology: Current understanding and future perspectives

Xia

Chen

Zeng

et al. 2019

152

126

“…Studies demonstrate melatonin ameliorates low‐grade inflammation and oxidative stress by repressing the inflammatory response in brain and peripheral tissues . Furthermore, melatonin could counteract the immune alterations and trigger an effective balance of innate and humoral immune response in immune cells . Exogenous melatonin enhances antigen presentation by splenic macrophages to T cells in mice .…”

Section: Introductionmentioning

confidence: 99%

“…[17][18][19] Furthermore, melatonin could counteract the immune alterations and trigger an effective balance of innate and humoral immune response in immune cells. [20][21][22] Exogenous melatonin enhances antigen presentation by splenic macrophages to T cells in mice. 23,24 Recent studies suggest that melatonin suppresses lipopolysaccharide (LPS)induced pro-inflammatory factors release in macrophages.…”

mentioning

confidence: 99%

Melatonin alleviates adipose inflammation through elevating α‐ketoglutarate and diverting adipose‐derived exosomes to macrophages in mice

Liu

Gan

Zhang

et al. 2017

139

114

Obesity is associated with macrophage infiltration and metabolic inflammation, both of which promote metabolic disease progression. Melatonin is reported to possess anti-inflammatory properties by inhibiting inflammatory response of adipocytes and macrophages activation. However, the effects of melatonin on the communication between adipocytes and macrophages during adipose inflammation remain elusive.Here, we demonstrated melatonin alleviated inflammation and elevated α-ketoglutarate (αKG) level in adipose tissue of obese mice. Mitochondrial isocitrate dehydrogenase 2 (Idh2) mRNA level was also elevated by melatonin in adipocytes leading to increase αKG level. Further analysis revealed αKG was the target for melatonin inhibition of adipose inflammation. Moreover, sirtuin 1 (Sirt1) physically interacted with IDH2 and formed a complex to increase the circadian amplitude of Idh2 and αKG content in melatonin-inhibited adipose inflammation. Notably, melatonin promoted exosomes secretion from adipocyte and increased adipose-derived exosomal αKG level. Our results also confirmed that melatonin alleviated adipocyte inflammation and increased ratio of M2 to M1 macrophages by transporting of exosomal αKG to macrophages and promoting TET-mediated DNA demethylation.Furthermore, exosomal αKG attenuated signal transducers and activators of transduction-3 (STAT3)/NF-κB signal by its receptor oxoglutarate receptor 1 (OXGR1) in adipocytes. Melatonin also attenuated adipose inflammation and deceased macrophage number in chronic jet-lag mice. In summary, our results demonstrate melatonin alleviates metabolic inflammation by increasing cellular and exosomal αKG level in adipose tissue. Our data reveal a novel function of melatonin on adipocytes and macrophages communication, suggesting a new potential therapy for melatonin to prevent and treat obesity caused systemic inflammatory disease.

“…The dose of melatonin was chosen based on previous studies where this drug was shown to reduce oxidative stress and improve the immune response. [41][42][43] Treatment started at the…”

Section: Animals and Treatmentmentioning

confidence: 99%

Effects of melatonin on thymic and oxidative stress dysfunctions during Trypanosoma cruzi infection

Brazão

Colato

Santello

et al. 2018

Self Cite

Although the exact etiology of Chagas disease is not completely elucidated, thymic atrophy and oxidative stress are believed to be important contributors to the pathogenesis during acute Trypanosoma cruzi (T. cruzi) infection. We hypothesized that exogenous melatonin, administered by gavage (5 mg/kg, p.o., gavage) to young (5 weeks old) and middle-aged (18 months old) male Wistar rats, would modulate thymic oxidative damage and reverse the age-related thymus regression during T. cruzi acute infection. Increased levels of superoxide anion (O ) were detected in the thymus of infected animals, and treatment with melatonin reverted this response. We found reduced TBARS levels as well as a significant increase in superoxide dismutase (SOD) activity in the thymus of all middle-aged melatonin-treated animals, infected or not with T. cruzi. Furthermore, melatonin increased the thymic expression of SOD1 and SOD2 in middle-aged control animals. Nox2 expression was not affected by melatonin treatment in young or middle-aged animals. Melatonin reverted the age-related thymic regression as revealed by the increase in thymus weight, total number of thymocytes, and reduction in age-related accumulation of double-negative thymocytes. This is the first report to directly examine the effects of melatonin treatment on the thymic antioxidant/oxidant status and thymic changes during T. cruzi infection. Our results revealed new antioxidant features that turn melatonin a potentially useful compound for the treatment of Chagas disease, a condition in which an excessive oxidative damage occurs.