title: Immunomodulatory properties and anti-apoptotic effects of zinc and melatonin in an experimental model of chronic Chagas disease.
abstract: The immunomodulatory effects of melatonin and zinc during chronic experimental Chagas' disease were studied. Early and late apoptosis by Annexin V-propidium iodide staining were evaluated. The expression of CD28, CD80, CD86, CD45RA and CD4(+)T and CD8(+)T cells were also evaluated by flow cytometry analysis. The combination of zinc and melatonin notably reduced the apoptotic ratios of splenic cells in the infected and treated animals when compared to untreated rats, during early and late stages of apoptosis. The percentages of CD8(+)T cells in Zn, Mel or Zn and Mel treated rats were reduced when compared to infected and untreated animals. Higher percentages of CD28 expression in CD4(+) and CD8(+) T cell populations were observed in control and infected Zn-treated group as compared to untreated ones. Zn, Mel or the combination of both did not induce any statistically significant differences for B cells when comparing to treated control and infected groups. Zinc or Mel-treated animals presented a lower expression of CD86 when compared to untreated counterparts. According to our data, this work strongly suggest that the modulation of the immune system operated by zinc and melatonin administration affected the balance among T cell immune response, apoptosis and expression of co-stimulatory molecules during chronic Trypanosoma cruzi infection, inducing important changes in the host's immune response against the parasite. Future experiments in this field should be focused in improving our understanding of the key mechanisms underlying the involvement of melatonin and zinc in the immune response during chronic Chagas' disease.
authors.affiliation: Laboratório de Parasitologia, Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto-Universidade de São Paulo, Avenida do Café s/n, 14040-903 Ribeirão Preto, SP, Brazil.
authors.forename: Vânia
authors.initials: V
authors.lastname: Brazão
authors.affiliation: Laboratório de Parasitologia, Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto-Universidade de São Paulo, Avenida do Café s/n, 14040-903 Ribeirão Preto, SP, Brazil.
authors.forename: Marina Del Vecchio
authors.initials: Mdel V
authors.lastname: Filipin
authors.affiliation: Laboratório de Parasitologia, Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto-Universidade de São Paulo, Avenida do Café s/n, 14040-903 Ribeirão Preto, SP, Brazil.
authors.forename: Fabricia Helena
authors.initials: FH
authors.lastname: Santello
authors.affiliation: Laboratório de Parasitologia, Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto-Universidade de São Paulo, Avenida do Café s/n, 14040-903 Ribeirão Preto, SP, Brazil.
authors.forename: Angela Palamin
authors.initials: AP
authors.lastname: Azevedo
authors.affiliation: Laboratório de Parasitologia, Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto-Universidade de São Paulo, Avenida do Café s/n, 14040-903 Ribeirão Preto, SP, Brazil.
authors.forename: Míriam Paula Alonso
authors.initials: MP
authors.lastname: Toldo
authors.affiliation: Laboratório de Parasitologia, Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto-Universidade de São Paulo, Avenida do Café s/n, 14040-903 Ribeirão Preto, SP, Brazil.
authors.forename: Fabiana Rossetto
authors.initials: FR
authors.lastname: de Morais
authors.affiliation: Laboratório de Parasitologia, Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto-Universidade de São Paulo, Avenida do Café s/n, 14040-903 Ribeirão Preto, SP, Brazil. Electronic address: jcprado@fcfrp.usp.br.
authors.forename: José Clóvis
authors.initials: JC
authors.lastname: do Prado
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D002469:Cell Separation; D014355:Chagas Disease; D002908:Chronic Disease; D004359:Drug Therapy, Combination; D005434:Flow Cytometry; D006801:Humans; D056747:Immunomodulation; D008297:Male; D008550:Melatonin / Q000008:administration & dosage*; D023421:Models, Animal; D051381:Rats; D017208:Rats, Wistar; D015032:Zinc / Q000008:administration & dosage*
chemical_list: D015703:Antigens, CD; D015032:Zinc; D008550:Melatonin
keywords: Apoptosis; Immune response; Melatonin; Trypanosoma cruzi; Zinc