title: Melatonin: Antioxidant and modulatory properties in age-related changes during Trypanosoma cruzi infection.
abstract: The purpose of this study was to investigate the effects of melatonin on selected biomarkers of innate and humoral immune response as well as the antioxidant/oxidant status (superoxide dismutase-SOD and reduced glutathione levels (GSH) to understand whether age-related changes would influence the development of acute Trypanosoma cruzi (T. cruzi) infection. Young- (5 weeks) and middle-aged (18 months) Wistar rats were orally treated with melatonin (gavage) (05 mg/kg/day), 9 days after infection. A significant increase in both SOD activity and GSH levels was found in plasma from all middle-aged melatonin-treated animals. Melatonin triggered enhanced expression of major histocompatibility class II (MHC-II) antigens on antigen-presenting cell (APC) and peritoneal macrophages in all treated animals. High levels of CD4+CD28-negative T cells (*P<.05) were detected in middle-aged control animals. Melatonin induced a significant reduction (***P<.001) in CD28-negative in CD4+and CD8+T cells in middle-aged control animals. Contrarily, the same group displayed upregulated CD4+CD28+T and CD8+CD28+T cells. Melatonin also triggered an upregulation of CD80 and CD86 expression in all young-treated groups. Significant percentages of B and spleen dendritic cells in middle-aged infected and treated animals were observed. Our data reveal new features of melatonin action in inhibiting membrane lipid peroxidation, through the reduction in 8-isoprostane, upregulating the antioxidant defenses and triggering an effective balance in the antioxidant/oxidant status during acute infection. The ability of melatonin to counteract the immune alterations induced by aging added further support to its use as a potential therapeutic target not only for T. cruzi infection but also for other immunocompromised states.
authors.affiliation: College of Pharmaceutical Sciences of Ribeirão Preto (FCFRP), University of São Paulo, Ribeirão Preto, SP, Brazil.
authors.forename: Vânia
authors.identifier: http://orcid.org/0000-0003-0149-4957
authors.initials: V
authors.lastname: Brazão
authors.affiliation: College of Pharmaceutical Sciences of Ribeirão Preto (FCFRP), University of São Paulo, Ribeirão Preto, SP, Brazil.
authors.forename: Fabricia H
authors.initials: FH
authors.lastname: Santello
authors.affiliation: College of Pharmaceutical Sciences of Ribeirão Preto (FCFRP), University of São Paulo, Ribeirão Preto, SP, Brazil.
authors.forename: Rafaela P
authors.initials: RP
authors.lastname: Colato
authors.affiliation: College of Pharmaceutical Sciences of Ribeirão Preto (FCFRP), University of São Paulo, Ribeirão Preto, SP, Brazil.
authors.forename: Tamires T
authors.initials: TT
authors.lastname: Mazotti
authors.affiliation: College of Pharmaceutical Sciences of Ribeirão Preto (FCFRP), University of São Paulo, Ribeirão Preto, SP, Brazil.
authors.forename: Lucas F
authors.initials: LF
authors.lastname: Tazinafo
authors.affiliation: College of Pharmaceutical Sciences of Ribeirão Preto (FCFRP), University of São Paulo, Ribeirão Preto, SP, Brazil.
authors.forename: Míriam Paula A
authors.initials: MPA
authors.lastname: Toldo
authors.affiliation: Department of Psychiatric Nursing and Human Sciences, Laboratory of Pharmacology, College of Nursing of Ribeirão Preto, USP, Ribeirão Preto, SP, Brazil.
authors.forename: Gabriel T
authors.initials: GT
authors.lastname: do Vale
authors.affiliation: Department of Psychiatric Nursing and Human Sciences, Laboratory of Pharmacology, College of Nursing of Ribeirão Preto, USP, Ribeirão Preto, SP, Brazil.
authors.forename: Carlos R
authors.initials: CR
authors.lastname: Tirapelli
authors.affiliation: College of Pharmaceutical Sciences of Ribeirão Preto (FCFRP), University of São Paulo, Ribeirão Preto, SP, Brazil.
authors.forename: José C
authors.initials: JC
authors.lastname: do Prado
mesh_terms: D000375:Aging; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D018106:CD28 Antigens / Q000378:metabolism; D014355:Chagas Disease / Q000276:immunology / Q000378:metabolism; D017737:Macrophages, Peritoneal / Q000187:drug effects; D008297:Male; D008550:Melatonin / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects*; D010088:Oxidoreductases / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000975:Antioxidants; D018106:CD28 Antigens; D010088:Oxidoreductases; D008550:Melatonin
keywords: 
  Trypanosoma cruzi
  ; antioxidant protection; immune response; melatonin