DNA damage and nitric oxide production in mice following infection with L. chagasi

Oliveira, Larissa Ragozo Cardoso de; Cezário, Glaucia Aparecida Gomes; Lima, Carlos Roberto Gonçalves de; Nicolete, Vanessa C; Peresi, Eliana; Síbio, Maria Tereza de; Picka, Mariele Cristina Modolo; Calvi, Sueli Aparecida

doi:10.1016/j.mrgentox.2011.04.009

Cited by 14 publications

(10 citation statements)

References 53 publications

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“…Other studies reported that parasites such as Trypanosoma cruzi, Toxoplasma gondii, and Opisthorchis viverrini also induce DNA damage (32-35). Our results are also consistent with those of Kocyigit et al (36) and de Oliveira et al (37), who observed DNA damage in patients with cutaneous leishmaniasis and in mice infected by Leishmania chagasi, respectively. These authors related the genotoxic effect to elevated NO generation during the control of Leishmania infection through the process known as the "oxidative burst," causing DNA damage in host cells by nitrative and oxidative lesions.…”

Section: Discussionsupporting

confidence: 93%

Meglumine Antimoniate (Glucantime) Causes Oxidative Stress-Derived DNA Damage in BALB/c Mice Infected by Leishmania (Leishmania) infantum

Moreira

Jesus

Soares

et al. 2017

Antimicrob Agents Chemother

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Leishmaniasis is a neglected tropical disease caused by Ͼ20 species of the protozoan parasite Leishmania. Meglumine antimoniate (Glucantime) is the firstchoice drug recommended by the World Health Organization for the treatment of all types of leishmaniasis. However, the mechanisms of action and toxicity of pentavalent antimonials, including genotoxic effects, remain unclear. Therefore, the mechanism by which meglumine antimoniate causes DNA damage was investigated for BALB/c mice infected by Leishmania (Leishmania) infantum and treated with meglumine antimoniate (20 mg/kg for 20 days). DNA damage was analyzed by a comet assay using mouse leukocytes. Furthermore, comet assays were followed by treatment with formamidopyrimidine-DNA glycosylase and endonuclease III, which remove oxidized DNA bases. In addition, the activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) in the animals' sera were assessed. To investigate mutagenicity, we carried out a micronucleus test. Our data demonstrate that meglumine antimoniate, as well as L. infantum infection, induces DNA damage in mammalian cells by the oxidation of nitrogenous bases. Additionally, the antileishmanial increased the frequency of micronucleated cells, confirming its mutagenic potential. According to our data, both meglumine antimoniate treatment and L. infantum infection promote oxidative stress-derived DNA damage, which promotes overactivation of the SOD-CAT axis, whereas the SOD-GPx axis is inhibited as a probable consequence of glutathione (GSH) depletion. Finally, our data enable us to suggest that a meglumine antimoniate regimen, as recommended by the World Health Organization, would compromise GPx activity, leading to the saturation of antioxidant defense systems that use thiol groups, and might be harmful to patients under treatment.

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Section: Discussionsupporting

confidence: 93%

Meglumine Antimoniate (Glucantime) Causes Oxidative Stress-Derived DNA Damage in BALB/c Mice Infected by Leishmania (Leishmania) infantum

Moreira

Jesus

Soares

et al. 2017

Antimicrob Agents Chemother

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“…Experimental studies on nourished animals inoculated with L. chagasi and Trypanosoma cruzi have demonstrated an increase in NO levels when compared to healthy animals. Our results disagree with these studies since higher NO production was observed in spontaneous culture of the healthy group (G4) compared to the inoculated nourished group (G3).…”

Section: Discussionmentioning

confidence: 99%

“…When studying malnourished animals inoculated with Leishmania donovani, these authors also found lower NO production in these animals compared to the healthy group. 31 Experimental studies on nourished animals inoculated with L. chagasi 32 and Trypanosoma cruzi 33 have demonstrated an increase in NO levels when compared to healthy animals. Our results disagree with these studies since higher NO production was observed in spontaneous culture of the healthy group (G4) compared to the inoculated nourished group (G3).…”

Section: Discussionmentioning

confidence: 99%

Nutritional status and immune response in murine experimental Jorge Lobo's disease

Barbosa

Diório

Pedrini

et al. 2015

Mycoses

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There are no studies investigating the role of nutritional status and immunity associated with Jorge Lobo's disease. The objective of this study was to evaluate the effects of protein-calorie malnutrition on the immune response of BALB/c mice inoculated with Lacazia loboi. In this study,the animals were divided into four groups: G1: inoculated with restricted diet, G2: not inoculated with restricted diet, G3: inoculated with regular diet, G4: not inoculated with regular diet. The animals of groups G1 and G2 were submitted to malnutrition for 20 days and once installed the animals were inoculated intradermally into the footpad. After 4 months, they were euthanised for the isolation of peritoneal lavage cells and removal of the footpad. The production of IL-2, IL-4, IL-10, IL-12, IFN-γ, TNF-α, H2 O2 and nitric oxide (NO) was evaluated in the peritoneal lavage cells. The footpad was evaluated regarding the size of macroscopic lesions, number of fungi and viability index. The results showed that the infection did not exert great influence on the body weight of the mice and previous malnutrition was an unfavourable factor for viability index, number of fungi, macroscopic lesion size in the footpad and production of H2 O2 , NO, IL-12, IL-10 and IFN-γ, suggesting that malnutrition significantly altered fungal activity and peritoneal cells. The results suggest considerable interaction between nutrition and immunity in Jorge Lobo's disease.

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“…The in vivo genotoxicity of intracellular parasites has been demonstrated in rodent peripheral blood [Ormiston et al, ; Ribeiro et al, ; de Oliveira et al, ]. The effect of infection on MN‐RET frequency by the coccidian Babesia microti was evaluated in male Syrian Golden hamsters where an increase in MN‐RET correlated with the extent of parasitemia.…”

Section: Discussionmentioning

confidence: 99%

Genotoxicity induced by Taenia solium and its reduction by immunization with calreticulin in a hamster model of taeniosis

Salazar

Mendlovic

Cruz-Rivera

et al. 2013

Environ and Mol Mutagen

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Genotoxicity induced by neurocysticercosis has been demonstrated in vitro and in vivo in humans. The adult stage of Taenia solium lodges in the small intestine and is the main risk factor to acquire neurocysticercosis, nevertheless its carcinogenic potential has not been evaluated. In this study, we determined the genotoxic effect of T. solium infection in the hamster model of taeniosis. In addition, we assessed the effect of oral immunization with recombinant T. solium calreticulin (rTsCRT) plus cholera toxin as adjuvant on micronuclei induction, as this protein has been shown to induce 33-44% protection in the hamster model of taeniosis. Blood samples were collected from the orbital venous plexus of noninfected and infected hamsters at different days postinfection, as well as from orally immunized animals, to evaluate the frequency of micronucleated reticulocytes as a measure of genotoxicity induced by parasite exposure and rTsCRT vaccination. Our results indicate that infection with T. solium caused time-dependent DNA damage in vivo and that rTsCRT immunization reduced the genotoxic damage induced by the presence of the tapeworms.

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DNA damage and nitric oxide production in mice following infection with L. chagasi

Cited by 14 publications

References 53 publications

Meglumine Antimoniate (Glucantime) Causes Oxidative Stress-Derived DNA Damage in BALB/c Mice Infected by Leishmania (Leishmania) infantum

Meglumine Antimoniate (Glucantime) Causes Oxidative Stress-Derived DNA Damage in BALB/c Mice Infected by Leishmania (Leishmania) infantum

Nutritional status and immune response in murine experimental Jorge Lobo's disease

Genotoxicity induced by Taenia solium and its reduction by immunization with calreticulin in a hamster model of taeniosis

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