title: Nonsteroidal anti-inflammatory is more effective than anti-oxidant therapy in counteracting oxidative/nitrosative stress and heart disease in T. cruzi-infected mice.
abstract: We compared the relevance of ibuprofen, vitamins C and E to control oxidative/nitrosative stress and heart disease in mice infected by Trypanosoma cruzi. Swiss mice were randomized into five groups: control, uninfected; infected without treatment; and infected treated with vitamins C, E or ibuprofen. Animals were inoculated with 2000 trypomastigote forms of T. cruzi. After 20 days, infected mice presented reduced vitamin C and E tissue levels, high cytokines (interferon gamma, tumour necrosis factor-α, interleukin 10 and chemokine ligand 2), prostaglandin F2α (PGF2α ) and nitric oxide (NO) cardiac production, intense myocarditis and reactive tissue damage, which was directly correlated with the intensity of the inflammatory infiltrate and the degree of pathological cardiac remodelling. Vitamins C and E supplementation were irrelevant to counteract reactive tissue damage and myocarditis in infected animals. Conversely, ibuprofen reduced tissue levels of cytokines, PGF2α and NO, as well as lipid and protein oxidation, antioxidant enzyme activity and the cardiac damage, without interfering with heart parasitism. Our results do not support the applicability of vitamin C and E supplementation in the management of acute Chagas cardiomyopathy. By controlling the inflammatory infiltrate, anti-inflammatory-based therapy proved to be a more rational strategy than a direct antioxidant therapy in attenuating oxidative/nitrosative stress and cardiac damage.
authors.affiliation: Department Structural Biology,Federal University of Alfenas,MG 37130-000,Brazil.
authors.forename: Rômulo D
authors.initials: RD
authors.lastname: Novaes
authors.affiliation: School of Medicine, Federal University of Jequitinhonha and Mucuri Valleys,MG 39100-000,Brazil.
authors.forename: Eliziária C
authors.initials: EC
authors.lastname: Santos
authors.affiliation: Department of Morphology,Federal University of Amazonas,AM 69077-000,Brazil.
authors.forename: Maria DO Carmo Q
authors.initials: MDCQ
authors.lastname: Fialho
authors.affiliation: Department of General Biology,Federal University of Viçosa,MG 36570-000,Brazil.
authors.forename: Wagner G
authors.initials: WG
authors.lastname: Gonçalves
authors.affiliation: Department of Pharmaceutical Sciences - Health Area,Federal University of Juiz de Fora,MG 35020-220,Brazil.
authors.forename: Priscila L
authors.initials: PL
authors.lastname: Sequetto
authors.affiliation: Department of Biological Sciences and NUPEB,Federal University of Ouro Preto,MG 34500-000,Brazil.
authors.forename: André
authors.initials: A
authors.lastname: Talvani
authors.affiliation: Department of Animal Biology,Federal University of Viçosa,MG 36570-000,Brazil.
authors.forename: Reggiani V
authors.initials: RV
authors.lastname: Gonçalves
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology / Q000627:therapeutic use*; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use*; D014355:Chagas Disease / Q000188:drug therapy* / Q000276:immunology / Q000469:parasitology; D004195:Disease Models, Animal; D008297:Male; D051379:Mice; D000073039:Nitrosative Stress; D014349:Trypanosoma cruzi / Q000187:drug effects
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000975:Antioxidants
keywords: Chagas disease; cardiovascular pathology; experimental therapeutics; oxidative stress