Treatment with melatonin induces a reduction of Toxoplasma gondii development in LLC-MK2 cells

Machado, Nayara Inocencio; Santos, Thiago Alves Teixeira dos; Souza, Wanderley de; DaMatta, Renato Augusto; Seabra, Sérgio Henrique

doi:10.1007/s00436-020-06766-5

Cited by 9 publications

(7 citation statements)

References 23 publications

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“…Therefore, tryptophan catabolites and their analogues might be used as effective therapeutic molecules to impair the regulatory processes leading to melatonin synthesis in the parasite. It should be underlined that the melatonin concentration used in the Majumdar et al [ 133 ] study was about ten times lower than in the Machado et al [ 132 ] experiment. Undoubtedly, melatonin metabolism in Toxoplasma gondii and in host cells requires further investigations.…”

Section: Melatonin and Lipid-soluble Vitamins In Toxoplasmosis Treatmentmentioning

confidence: 89%

“…To our best knowledge, there exist only two studies concerning the direct effects of melatonin on Toxoplasma development after in vitro infection of host cells. In the research of Machado et al [ 132 ], the effects of melatonin treatment in the monkey kidney cell epithelial line LLC-MK2 after infection with T. gondii were analyzed. Melatonin reduced parasite proliferation in the LLC-MK2 cells at 24 and 48 h and at 6 days.…”

Section: Melatonin and Lipid-soluble Vitamins In Toxoplasmosis Treatmentmentioning

confidence: 99%

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Oxidative Stress as a Possible Target in the Treatment of Toxoplasmosis: Perspectives and Ambiguities

Szewczyk-Golec¹,

Pawłowska²,

Wesołowski³

et al. 2021

IJMS

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Toxoplasma gondii is an apicomplexan parasite causing toxoplasmosis, a common disease, which is most typically asymptomatic. However, toxoplasmosis can be severe and even fatal in immunocompromised patients and fetuses. Available treatment options are limited, so there is a strong impetus to develop novel therapeutics. This review focuses on the role of oxidative stress in the pathophysiology and treatment of T. gondii infection. Chemical compounds that modify redox status can reduce the parasite viability and thus be potential anti-Toxoplasma drugs. On the other hand, oxidative stress caused by the activation of the inflammatory response may have some deleterious consequences in host cells. In this respect, the potential use of natural antioxidants is worth considering, including melatonin and some vitamins, as possible novel anti-Toxoplasma therapeutics. Results of in vitro and animal studies are promising. However, supplementation with some antioxidants was found to promote the increase in parasitemia, and the disease was then characterized by a milder course. Undoubtedly, research in this area may have a significant impact on the future prospects of toxoplasmosis therapy.

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Section: Melatonin and Lipid-soluble Vitamins In Toxoplasmosis Treatmentmentioning

confidence: 89%

Section: Melatonin and Lipid-soluble Vitamins In Toxoplasmosis Treatmentmentioning

confidence: 99%

Oxidative Stress as a Possible Target in the Treatment of Toxoplasmosis: Perspectives and Ambiguities

Szewczyk-Golec¹,

Pawłowska²,

Wesołowski³

et al. 2021

IJMS

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“…Although at concentrations in the mM range, MLT has been found to inhibit Toxoplasma gondii growth in a monkey kidney cell line culture without affecting host cells’ viability. The authors suggested that MLT reduced parasite growth, inducing both apoptosis and necrosis by modifying energy metabolism [ 110 ]. An opposite finding was reported in a human colon adenocarcinoma cell line, where 0.2 nM of MLT was proved to boost parasite replication.…”

Section: Mlt and Parasitic Infectionsmentioning

confidence: 99%

Role of Melatonin in Viral, Bacterial and Parasitic Infections

Maestroni

2024

Biomolecules

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In all mammals, the circulating pool of MLTs is synthesized in the pineal gland during the night’s darkness hours. Its main function is synchronizing the organism in the photoperiod. In contrast, extra-pineal MLT is synthesized in peripheral organs, does not follow any circadian rhythm or circulate, and plays a detoxifying and cytoprotective role. Circulating MLT may stimulate both innate and acquired immune responses through its circadian action and by activating high-affinity receptors on immunocompetent cells. Extra-pineal MLT may have antioxidant and anti-inflammatory effects that dampen the innate immune response. These two seemingly divergent roles may be considered to be two sides of the same coin. In fact, the integration of both circulating and extra-pineal MLT functions might generate a balanced and effective immune response against microbial pathogens. The studies described in this review investigated the effects of exogenous MLT in various models of infectious diseases using extremely different doses and treatment schedules. None of them evaluated the possibility of integrating the non-circadian anti-inflammatory effect with the circadian immunoenhancing action of MLT. As a consequence, in spite of the fact that most studies agree that MLT has a beneficial effect against infections, it seems difficult to draw any definite conclusion about its possible therapeutic use.

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“…Melatonin suppressed the development of Plasmodium parasites in malaria due to regulation of cAMP-PKA and IP3-Ca 2+ signaling pathways [195][196][197][198]. In Chagas' disease [199], toxoplasmosis [200] and African trypanosomiasis [201], melatonin stimulated the host's immune response against the parasite, up-regulating the production of inflammatory mediators. Melatonin inhibited leishmaniasis parasite replication via direct effects on mitochondrial functions-activating the efflux of Ca 2+ from mitochondria, increasing the level of mitochondrial nitrites, and suppressing the superoxide dismutase activity [202].…”

Section: The Role Of Melatonin In the Treatment Of The Protozoan Parasitic Infectionsmentioning

confidence: 99%

Molecular Mechanisms of Melatonin-Mediated Cell Protection and Signaling in Health and Disease

Kopustinskienė

Bernatonienė

2021

Pharmaceutics

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Melatonin, an endogenously synthesized indolamine, is a powerful antioxidant exerting beneficial action in many pathological conditions. Melatonin protects from oxidative stress in ischemic/reperfusion injury, neurodegenerative diseases, and aging, decreases inflammation, modulates the immune system, inhibits proliferation, counteracts the Warburg effect, and promotes apoptosis in various cancer models. Melatonin stimulates antioxidant enzymes in the cells, protects mitochondrial membrane phospholipids, especially cardiolipin, from oxidation thus preserving integrity of the membranes, affects mitochondrial membrane potential, stimulates activity of respiratory chain enzymes, and decreases the opening of mitochondrial permeability transition pore and cytochrome c release. This review will focus on the molecular mechanisms of melatonin effects in the cells during normal and pathological conditions and possible melatonin clinical applications.

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Treatment with melatonin induces a reduction of Toxoplasma gondii development in LLC-MK2 cells

Cited by 9 publications

References 23 publications

Oxidative Stress as a Possible Target in the Treatment of Toxoplasmosis: Perspectives and Ambiguities

Oxidative Stress as a Possible Target in the Treatment of Toxoplasmosis: Perspectives and Ambiguities

Role of Melatonin in Viral, Bacterial and Parasitic Infections

Molecular Mechanisms of Melatonin-Mediated Cell Protection and Signaling in Health and Disease

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