title: DNA damage and nitric oxide production in mice following infection with L. chagasi.
abstract: Leishmania chagasi, which causes visceral leishmaniasis in South America, is an obligate intracellular protozoan. Production of nitric oxide by macrophages during the inflammatory response is one of the main microbicidal mechanisms against this parasite. The goal of this study was to evaluate whether L. chagasi infection causes DNA damage in peripheral blood and spleen cells of Balb/c mice and whether such damage may be related to NO production. Balb/c mice were either infected with L. chagasi or maintained as controls. The single-cell gel electrophoresis (comet) assay was used to measure DNA damage in peripheral blood and spleen cells, and the Griess reaction was used to measure NO production in the spleen. L. chagasi infection induced DNA damage in peripheral blood and spleen cells of infected mice. Macrophages from the control group, challenged with L. chagasi, showed significantly (p<0.05) greater NO production, compared to non-challenged cells. Treatment of spleen cells with N(G)-monomethyl-l-arginine (LNMMA) caused a significant reduction of NO production and DNA damage (p<0.05). Our results indicate that L. chagasi induces DNA damage in the peripheral blood and spleen cells and that NO not only causes killing of the parasite but also induces DNA damage in adjacent cells.
authors.affiliation: Tropical Diseases Department, Faculdade de Medicina de Botucatu - UNESP, São Paulo State University, Brazil. larissaragozo@yahoo.com.br
authors.forename: Larissa Ragozo Cardoso
authors.initials: LR
authors.lastname: de Oliveira
authors.forename: Gláucia Aparecida Gomes
authors.initials: GA
authors.lastname: Cezário
authors.forename: Carlos Roberto Gonçalves
authors.initials: CR
authors.lastname: de Lima
authors.forename: Vanessa Cristina
authors.initials: VC
authors.lastname: Nicolete
authors.forename: Eliana
authors.initials: E
authors.lastname: Peresi
authors.forename: Maria Tereza
authors.initials: MT
authors.lastname: de Síbio
authors.forename: Mariele Cristina Modolo
authors.initials: MC
authors.lastname: Picka
authors.forename: Sueli Aparecida
authors.initials: SA
authors.lastname: Calvi
mesh_terms: D000818:Animals; D004249:DNA Damage; D005260:Female; D007898:Leishmaniasis, Visceral / Q000097:blood / Q000235:genetics* / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism / Q000469:parasitology; D051379:Mice; D008807:Mice, Inbred BALB C; D009569:Nitric Oxide / Q000096:biosynthesis*; D013154:Spleen / Q000378:metabolism / Q000469:parasitology; D019323:omega-N-Methylarginine / Q000494:pharmacology
chemical_list: D019323:omega-N-Methylarginine; D009569:Nitric Oxide