RESUMO
Regular physical exercise has been described as a good strategy for prevention or reduction of musculoskeletal pain. The Peroxisome Proliferator-Activated Receptor Gamma (PPARγ) has been investigated as a promising target for the control of inflammatory pain. Therefore, the aim of this study was to evaluate whether activation of PPARγ receptors is involved in the reduction of acute muscle pain by chronic exercise and, in this case, whether this process is modulated by inflammatory cytokines. To this end, Wistar rats were submitted to swimming physical training for a period of 10â¯weeks, 5â¯days per week, 40â¯min/day, in an intensity of 4% of the body mass. Muscle hyperalgesia was measured by Randall Selitto test and pro-inflammatory cytokines were quantified by ELISA. The results showed that swimming physical training prevented the onset of acute mechanical muscle hyperalgesia and the increase in muscle levels of Cytokine-induced neutrophil chemoattractant 1 (CINC-1) induced by carrageenan into gastrocnemius muscle. In addition, local pre-treatment with the selective PPARγ receptors antagonist GW9662 reversed the mechanical muscle hypoalgesia and the modulation of CINC-1 levels induced by swimming physical training. These data suggest that swimming physical training prevented the onset of acute mechanical muscle hyperalgesia by a mechanism dependent of PPARγ receptors, which seems to contribute to this process by modulation of the pro-inflammatory cytokine CINC-1, and highlight the potential of PPARγ receptors as a target to control musculoskeletal pain and to potentiate the reduction of musculoskeletal pain induced by exercise.
Assuntos
Quimiocina CXCL1/metabolismo , Hiperalgesia/prevenção & controle , Mialgia/prevenção & controle , PPAR gama/metabolismo , Natação/fisiologia , Anilidas/farmacologia , Animais , Citocinas/metabolismo , Masculino , Mialgia/induzido quimicamente , Mialgia/metabolismo , Nociceptividade/efeitos dos fármacos , Nociceptividade/fisiologia , Ratos , Ratos WistarRESUMO
The classic model of fever induction is based on the administration of lipopolysaccharide (LPS) from Gram-negative bacteria in experimental animals. LPS-induced fever results in the synthesis/release of many mediators that assemble an LPS-fever cascade. We have previously demonstrated that cytokine-induced neutrophil chemoattractant (CINC)-1, a Glu-Leu-Arg (ELR) + chemokine, centrally administered to rats, induces fever and increases prostaglandin E2 in the cerebrospinal fluid. We now attempt to investigate the involvement of CINC-1 and its functional receptor CXCR2 on the fever induced by exogenous and endogenous pyrogens in rats. We also investigated the effect of reparixin, an allosteric inhibitor of CXCR1/CXCR2 receptors, on fever induced by either systemic administration of LPS or intracerebroventricular injection of CINC-1, as well as TNF-α, IL-1ß, IL-6, or ET-1, known mediators of febrile response. Our results show increased CINC-1 mRNA expression in the liver, hypothalamus, CSF, and plasma following LPS injection. Moreover, reparixin administered right before CINC-1 or LPS abolished the fever induced by CINC-1 and significantly reduced the response induced by LPS. In spite of these results, reparixin does not modify the fever induced by IL-1ß, TNF-α, and IL-6, but significantly reduces ET-1-induced fever. Therefore, it is plausible to suggest that CINC-1 might contribute to LPS-induced fever in rats by activating CXCR2 receptor on the CNS. Moreover, it can be hypothesized that CINC-1 is placed upstream TNF-α, IL-1ß, and IL-6 among the prostaglandin-dependent fever-mediator cascade and amidst the prostaglandin-independent synthesis pathway of fever.
Assuntos
Quimiocina CXCL1/metabolismo , Febre/induzido quimicamente , Febre/metabolismo , Lipopolissacarídeos/farmacologia , Receptores de Interleucina-8B/metabolismo , Animais , Líquido Cefalorraquidiano/efeitos dos fármacos , Líquido Cefalorraquidiano/metabolismo , Hipotálamo/efeitos dos fármacos , Hipotálamo/metabolismo , Interleucina-6/metabolismo , Interleucina-8/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Masculino , Prostaglandinas/metabolismo , RNA Mensageiro/metabolismo , Ratos , Ratos Wistar , Linfócitos T/efeitos dos fármacos , Linfócitos T/metabolismo , Fator de Necrose Tumoral alfa/metabolismoRESUMO
INTRODUCTION: The antibacterial effect of ozone (O(3)) has been described in the extant literature, but the role of O(3) therapy in the treatment of certain types of infection remains controversial. OBJECTIVES: To evaluate the effect of intraperitoneal (i.p.) O(3) application in a cecal ligation/puncture rat model on interleukins (IL-6, IL-10) and cytokine-induced neutrophil chemoattractant (CINC)-1 serum levels, acute lung injury and survival rates. METHODS: FOUR ANIMAL GROUPS WERE USED FOR THE STUDY: a) the SHAM group underwent laparotomy; b) the cecal ligation/puncture group underwent cecal ligation/puncture procedures; and c) the CLP+O(2) and CLP+O(3) groups underwent CLP+ corresponding gas mixture infusions (i.p.) throughout the observation period. IL-6, CINC-1 and IL-10 concentrations were determined by enzyme-linked immunosorbent assay (ELISA). Acute lung injury was evaluated with the Evans blue dye lung leakage method and by lung histology. P<0.05 was considered significant. RESULTS: CINC-1 was at the lowest level in the SHAM group and was lower for the CLP+O(3) group vs. the CLP+O(2) group and the cecal ligation/puncture group. IL-10 was lower for the SHAM group vs. the other three groups, which were similar compared to each other. IL-6 was lower for the SHAM group vs. all other groups, was lower for the CLP+O(3) or CLP+O(2) group vs. the cecal ligation/puncture group, and was similar for the CLP+O(3) group vs. the CLP+O(2) group. The lung histology score was lower for the SHAM group vs. the other groups. The Evans blue dye result was lower for the CLP+O(3) group vs. the CLP+O(2) group and the cecal ligation/puncture group but similar to that of the SHAM group. The survival rate for the CLP+O(3) group was lower than for the SHAM group and similar to that for the other 2 groups (CLP and CLP+O(2)). CONCLUSION: Ozone therapy modulated the inflammatory response and acute lung injury in the cecal ligation/puncture infection model in rats, although there was no improvement on survival rates.
Assuntos
Quimiocina CXCL1/sangue , Interleucina-10/sangue , Interleucina-6/sangue , Ozônio/uso terapêutico , Peritonite/tratamento farmacológico , Sepse/tratamento farmacológico , Animais , Ceco/cirurgia , Modelos Animais de Doenças , Ensaio de Imunoadsorção Enzimática , Ligadura , Masculino , Peritonite/sangue , Punções , Ratos , Ratos Wistar , Sepse/sangueRESUMO
INTRODUCTION: The antibacterial effect of ozone (O3) has been described in the extant literature, but the role of O3 therapy in the treatment of certain types of infection remains controversial. OBJECTIVES: To evaluate the effect of intraperitoneal (i.p.) O3 application in a cecal ligation/puncture rat model on interleukins (IL-6, IL-10) and cytokine-induced neutrophil chemoattractant (CINC)-1 serum levels, acute lung injury and survival rates. METHODS: Four animal groups were used for the study: a) the SHAM group underwent laparotomy; b) the cecal ligation/puncture group underwent cecal ligation/puncture procedures; and c) the CLP+O2 and CLP+O3 groups underwent CLP+ corresponding gas mixture infusions (i.p.) throughout the observation period. IL-6, CINC-1 and IL-10 concentrations were determined by enzyme-linked immunosorbent assay (ELISA). Acute lung injury was evaluated with the Evans blue dye lung leakage method and by lung histology. P<0.05 was considered significant. RESULTS: CINC-1 was at the lowest level in the SHAM group and was lower for the CLP+O3 group vs. the CLP+O2 group and the cecal ligation/puncture group. IL-10 was lower for the SHAM group vs. the other three groups, which were similar compared to each other. IL-6 was lower for the SHAM group vs. all other groups, was lower for the CLP+O3 or CLP+O2 group vs. the cecal ligation/puncture group, and was similar for the CLP+O3 group vs. the CLP+O2 group. The lung histology score was lower for the SHAM group vs. the other groups. The Evans blue dye result was lower for the CLP+O3 group vs. the CLP+O2 group and the cecal ligation/puncture group but similar to that of the SHAM group. The survival rate for the CLP+O3 group was lower than for the SHAM group and similar to that for the other 2 groups (CLP and CLP+O2). CONCLUSION: Ozone therapy modulated the inflammatory response and acute lung injury in the cecal ligation/puncture infection model in rats, although there was no ...