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Melatonin attenuates L eishmania (L.) amazonensis infection by modulating arginine metabolism
Author(s) -
LaranjeiraSilva Maria Fernanda,
Zampieri Ricardo A.,
Muxel Sandra M.,
FloeterWinter Lucile Maria,
Markus Regina P.
Publication year - 2015
Publication title -
journal of pineal research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.881
H-Index - 131
eISSN - 1600-079X
pISSN - 0742-3098
DOI - 10.1111/jpi.12279
Subject(s) - melatonin , biology , luzindole , medicine , endocrinology , pineal gland , circadian rhythm , leishmania major , melatonin receptor , leishmania , pharmacology , parasite hosting , world wide web , computer science
Acute inflammatory responses induced by bacteria or fungi block nocturnal melatonin synthesis by rodent pineal glands. Here, we show Leishmania infection does not impair daily melatonin rhythm in hamsters. Remarkably, the attenuated parasite burden and lesion progression in hamsters infected at nighttime was impaired by blockage of melatonin receptors with luzindole, whereas melatonin treatment during the light phase attenuated Leishmania infection. In vitro studies corroborated in vivo observations. Melatonin treatment reduced macrophage expression of C at‐2b , Cat1, and ArgI , genes involved in arginine uptake and polyamine synthesis. Indeed, melatonin reduced macrophage arginine uptake by 40%. Putrescine supplementation reverted the attenuation of infectivity by melatonin indicating that its effect was due to the arrest of parasite replication. This study shows that the Leishmania /host interaction varies in a circadian manner according to nocturnal melatonin pineal synthesis. Our results provide new data regarding Leishmania infectiveness and show new approaches for applying agonists of melatonin receptors in Leishmaniasis therapy.