RESUMO
OBJECTIVES: To evaluate the analgesic effect of Glucantime (antimoniate N-methylglucamine) in Leishmania amazonensis infection and complete Freund's adjuvant (CFA), chronic paw inflammation model, in BALB/c mice. METHODS: Two models of chronic inflammatory pain in BALB/c mice paw were used: infection with L. amazonensis and CFA stimulation. Both animals models received daily treatment with Glucantime (10 mg/kg, i.p.) and during the treatment was measured the mechanical hyperalgesia with electronic version of von Frey filaments. After the treatment, the paw skin sample was collected for analysis of myeloperoxidase (MPO) and N-acetyl-ß-glucosaminidase (NAG) activity, and IL-1ß, TNF-α, IL-6, IFN-γ and IL-10 cytokines production by ELISA. KEY FINDINGS: Leishmania amazonensis-induced chronic inflammation with significant increase in mechanical hyperalgesia, MPO and NAG activity, and IL-1ß, TNF-α and IL-6 production in the paw skin. Glucantime (10 mg/kg, i.p.) inhibited L. amazonensis-induced mechanical hyperalgesia and IL-1ß and IL-6 cytokines productions. In chronic inflammatory model induced by CFA, Glucantime treatment during 7 days inhibited CFA-induced mechanical hyperalgesia, MPO and NAG activity, and IL-1ß, TNF-α, IL-6 and IFN-γ production as well as increased IL-10 production. CONCLUSIONS: Our data demonstrated that Glucantime reduced the chronic inflammatory pain induced by L. amazonensis and CFA stimuli by inhibiting the hyperalgesic cytokines production.
Assuntos
Dor Crônica/tratamento farmacológico , Inflamação/tratamento farmacológico , Leishmaniose Cutânea/tratamento farmacológico , Meglumina/uso terapêutico , Compostos Organometálicos/uso terapêutico , Acetilglucosaminidase/metabolismo , Animais , Dor Crônica/complicações , Citocinas/metabolismo , Adjuvante de Freund , Inflamação/induzido quimicamente , Inflamação/complicações , Masculino , Antimoniato de Meglumina , Camundongos , Peroxidase/metabolismo , Pele/metabolismoRESUMO
Experimental models of mouse paw infection with L. amazonensis show an induction of a strong inflammatory response in the skin, and parasitic migration may occur to secondary organs with consequent tissue injury. There are few studies focusing on the resolution of damage in secondary organs caused by Leishmania species-related cutaneous leishmaniasis. We investigated the propolis treatment effect on liver inflammation induced by Leishmania amazonensis infection in the mouse paw. BALB/c mice were infected in the hind paw with L. amazonensis (10(7)) promastigote forms. After 15 days, animals were treated daily with propolis (5 mg/kg), Glucantime (10 mg/kg), or with propolis plus Glucantime combined. After 60 days, mice were euthanized and livers were collected for inflammatory process analysis. Liver microscopic analysis showed that propolis reduced the inflammatory process compared to untreated infected control. There was a decrease of liver myeloperoxidase and N-acetyl-ß-glucosaminidase activity levels, collagen fiber deposition, pro-inflammatory cytokine production, and plasma aspartate transaminase and alanine transaminase levels. Furthermore, propolis treatment enhanced anti-inflammatory cytokine levels and reversed hepatosplenomegaly. Our data demonstrated that daily low doses of Brazilian propolis reduced the secondary chronic inflammatory process in the liver caused by L. amazonensis subcutaneous infection in a susceptible mice strain.