RESUMO
Oxaliplatin is a third-generation platinum drug commonly used as the first line treatment of metastatic colorectal cancer. Oxaliplatin-based anticancer regimens course with dose-limiting neurotoxicity. The pharmacological strategies used to manage such side effect are not totally effective. Metformin is an anti-diabetic drug that is described to negatively modulate painful diabetic neuropathy. Then, this study aimed to assess the effect of metformin in the oxaliplatin-induced peripheral sensory neuropathy in mice. For that purpose, Swiss male mice were injected with oxaliplatin (1, 2 or 4 mg/kg, i.v., twice a week with a total of nine injections) alone or in combination with daily administration of metformin (250 mg/kg, p.o.). Thermal and mechanical nociceptive tests were performed once a week for five weeks. Then, the animals were euthanized on day 35 post-first injection of oxaliplatin and the dorsal root ganglia were harvested for the assessment of c-Fos and ATF3 expressions. Oxaliplatin caused a nociceptive response accompanied by the increased expression of c-Fos and ATF3 in the dorsal root ganglia and spinal cord. In addition, the oxaliplatin-associated nociception was significantly attenuated by metformin (P < 0.05), which also reduced the expression of c-Fos and ATF3 (P < 0.05). Therefore, metformin protected from the peripheral sensory neuropathy induced by oxaliplatin, which was confirmed by the reduction of c-Fos and ATF3 expression, two known neuronal activation and damage markers, respectively.
Assuntos
Fator 3 Ativador da Transcrição/antagonistas & inibidores , Gânglios Espinais/metabolismo , Metformina/uso terapêutico , Oxaliplatina/toxicidade , Doenças do Sistema Nervoso Periférico/metabolismo , Proteínas Proto-Oncogênicas c-fos/antagonistas & inibidores , Fator 3 Ativador da Transcrição/biossíntese , Fator 3 Ativador da Transcrição/genética , Animais , Antineoplásicos/toxicidade , Gânglios Espinais/efeitos dos fármacos , Expressão Gênica , Hipoglicemiantes/farmacologia , Hipoglicemiantes/uso terapêutico , Masculino , Metformina/farmacologia , Camundongos , Doenças do Sistema Nervoso Periférico/tratamento farmacológico , Doenças do Sistema Nervoso Periférico/genética , Proteínas Proto-Oncogênicas c-fos/biossíntese , Proteínas Proto-Oncogênicas c-fos/genéticaRESUMO
PURPOSE: To study the anti-inflammatory actions of electroacupuncture (EAc) on an experimental colitis model in mice. METHODS: Thirty-eight male Swiss mice, divided in five groups, were subjected to induction of colitis by TNBS in 50% ethanol. Saline (SAL) and ethanol (ETNL) groups served as controls. TNBS+EAc and TNBS+ dexamethasone subgroups were treated with EAc 100Hz and dexamethasone (DEXA) 1 mg/Kg/day, respectively. After three days, a colon segment was obtained for quantification of myeloperoxidase (MPO) activity, immunohistochemistry for iNOS, malondialdehyde (MDA) and cytokines (IL-1ß and IL-10). RESULTS: Neutrophilic activity, assayed as MPO activity, was significantly higher in the TNBS colitis group than that in the saline control group. TNBS+EAc group showed suppression of IL-10 in the colon. EAc treatment significantly reduced the concentration of MDA and the expression of iNOS, as compared to the other groups. CONCLUSION: Electroacupuncture 100Hz applied to acupoint ST-36 promotes an anti-inflammatory action on the TNBS-induced colitis, mediated by increase of IL-10 and decrease of iNOS expression.
Assuntos
Anti-Inflamatórios/uso terapêutico , Colite/terapia , Eletroacupuntura/métodos , Interleucina-10/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Peroxidase/metabolismo , Pontos de Acupuntura , Animais , Colite/induzido quimicamente , Colo/metabolismo , Modelos Animais de Doenças , Imuno-Histoquímica , Doenças Inflamatórias Intestinais/tratamento farmacológico , Doenças Inflamatórias Intestinais/terapia , Interleucina-1beta/metabolismo , Masculino , Malondialdeído/metabolismo , Camundongos , Óxido Nítrico Sintase Tipo II/antagonistas & inibidores , Distribuição Aleatória , Ácido TrinitrobenzenossulfônicoRESUMO
PURPOSE: To study the anti-inflammatory actions of electroacupuncture (EAc) on an experimental colitis model in mice. METHODS: Thirty-eight male Swiss mice, divided in five groups, were subjected to induction of colitis by TNBS in 50% ethanol. Saline (SAL) and ethanol (ETNL) groups served as controls. TNBS+EAc and TNBS+ dexamethasone subgroups were treated with EAc 100Hz and dexamethasone (DEXA) 1 mg/Kg/day, respectively. After three days, a colon segment was obtained for quantification of myeloperoxidase (MPO) activity, immunohistochemistry for iNOS, malondialdehyde (MDA) and cytokines (IL-1β and IL-10). RESULTS: Neutrophilic activity, assayed as MPO activity, was significantly higher in the TNBS colitis group than that in the saline control group. TNBS+EAc group showed suppression of IL-10 in the colon. EAc treatment significantly reduced the concentration of MDA and the expression of iNOS, as compared to the other groups. CONCLUSION: Electroacupuncture 100Hz applied to acupoint ST-36 promotes an anti-inflammatory action on the TNBS-induced colitis, mediated by increase of IL-10 and decrease of iNOS expression. .
Assuntos
Animais , Masculino , Camundongos , Anti-Inflamatórios/uso terapêutico , Colite/terapia , Eletroacupuntura/métodos , /metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Peroxidase/metabolismo , Pontos de Acupuntura , Colite/induzido quimicamente , Colo/metabolismo , Modelos Animais de Doenças , Imuno-Histoquímica , Doenças Inflamatórias Intestinais/tratamento farmacológico , Doenças Inflamatórias Intestinais/terapia , Interleucina-1beta/metabolismo , Malondialdeído/metabolismo , Óxido Nítrico Sintase Tipo II/antagonistas & inibidores , Distribuição Aleatória , Ácido TrinitrobenzenossulfônicoRESUMO
PURPOSE:To study the anti-inflammatory actions of electroacupuncture (EAc) on an experimental colitis model in mice.METHODS:Thirty-eight male Swiss mice, divided in five groups, were subjected to induction of colitis by TNBS in 50% ethanol. Saline (SAL) and ethanol (ETNL) groups served as controls. TNBS+EAc and TNBS+ dexamethasone subgroups were treated with EAc 100Hz and dexamethasone (DEXA) 1 mg/Kg/day, respectively. After three days, a colon segment was obtained for quantification of myeloperoxidase (MPO) activity, immunohistochemistry for iNOS, malondialdehyde (MDA) and cytokines (IL-1β and IL-10).RESULTS:Neutrophilic activity, assayed as MPO activity, was significantly higher in the TNBS colitis group than that in the saline control group. TNBS+EAc group showed suppression of IL-10 in the colon. EAc treatment significantly reduced the concentration of MDA and the expression of iNOS, as compared to the other groups. CONCLUSION: Electroacupuncture 100Hz applied to acupoint ST-36 promotes an anti-inflammatory action on the TNBS-induced colitis, mediated by increase of IL-10 and decrease of iNOS expression.
Assuntos
Animais , Camundongos , Colite/induzido quimicamente , Eletroacupuntura/veterinária , Trinitrobenzenos , Óxido Nítrico SintaseRESUMO
PURPOSE:To study the anti-inflammatory actions of electroacupuncture (EAc) on an experimental colitis model in mice.METHODS:Thirty-eight male Swiss mice, divided in five groups, were subjected to induction of colitis by TNBS in 50% ethanol. Saline (SAL) and ethanol (ETNL) groups served as controls. TNBS+EAc and TNBS+ dexamethasone subgroups were treated with EAc 100Hz and dexamethasone (DEXA) 1 mg/Kg/day, respectively. After three days, a colon segment was obtained for quantification of myeloperoxidase (MPO) activity, immunohistochemistry for iNOS, malondialdehyde (MDA) and cytokines (IL-1β and IL-10).RESULTS:Neutrophilic activity, assayed as MPO activity, was significantly higher in the TNBS colitis group than that in the saline control group. TNBS+EAc group showed suppression of IL-10 in the colon. EAc treatment significantly reduced the concentration of MDA and the expression of iNOS, as compared to the other groups. CONCLUSION: Electroacupuncture 100Hz applied to acupoint ST-36 promotes an anti-inflammatory action on the TNBS-induced colitis, mediated by increase of IL-10 and decrease of iNOS expression.(AU)