RESUMO
Nrf2 is the key transcription factor regulating the antioxidant response which is crucial for cytoprotection against extracellular stresses. Numerous in vivo studies indicate that Nrf2 plays a protective role in anti-inflammatory response. 3-(3-Pyridylmethylidene)-2-indolinone (PMID) is a synthesized derivative of 2-indolinone compounds. Our previous study suggested that PMID induces the activation of Nrf2/ARE pathway, then protecting against oxidative stress-mediated cell death. However, little is known regarding the anti-inflammatory properties of PMID in severe inflammatory phenotypes. In the present study we determined if PMID treatment protects mice from dextran sodium sulphate- (DSS-) induced colitis. The result suggests that treatment with PMID prior to colitis induction significantly reduced body weight loss, shortened colon length, and decreased disease activity index compared to control mice. Histopathological analysis of the colon revealed attenuated inflammation in PMID pretreated animals. The levels of inflammatory markers in colon tissue and serum were reduced associated with inhibition of NF-κB activation. The expression levels of Nrf2-dependent genes such as HO-1, NQO1, and Nrf2 were increased in PMID pretreated mice. However, PMID pretreatment did not prevent DSS-induced colitis in Nrf2 knockout mice. These data indicate that PMID pretreatment in mice confers protection against DSS-induced colitis in Nrf2-dependent manner, suggesting a potential role of PMID in anti-inflammatory response.
Assuntos
Anti-Inflamatórios/uso terapêutico , Colite/tratamento farmacológico , Indóis/uso terapêutico , Piridinas/uso terapêutico , Animais , Anti-Inflamatórios/síntese química , Anti-Inflamatórios/farmacologia , Colite/induzido quimicamente , Colite/patologia , Colo/efeitos dos fármacos , Colo/patologia , Colo/fisiologia , Citocinas/análise , Citocinas/genética , Sulfato de Dextrana/toxicidade , Modelos Animais de Doenças , Ensaio de Imunoadsorção Enzimática , Heme Oxigenase-1/genética , Heme Oxigenase-1/metabolismo , Indóis/síntese química , Indóis/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos ICR , Camundongos Knockout , NAD(P)H Desidrogenase (Quinona)/genética , NAD(P)H Desidrogenase (Quinona)/metabolismo , Fator 2 Relacionado a NF-E2/deficiência , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , NF-kappa B/metabolismo , Piridinas/síntese química , Piridinas/farmacologia , Índice de Gravidade de DoençaRESUMO
Adsorption performance of 5 GACs were compared on two abundant haloacetic acids (HAAs) as disinfection by-products (dichloroacetic acid and trichloroacetic acid). The adsorption behaviours of the two HAAs were well correlated with Langmuir equation. When the two HAAs co-existed, trichloroacetic acid tended to be adsorbed more easily. The adsorption capacity of a foreign GAC-A for dichloroacetic acid was 4.4-5.7 times that of domestic GACs, and 3.8 times that of another foreign GAC-B, while the adsorption capacity of a foreign GAC-A for trichloroacetic acid was 4.0-5.4 times that of domestic GACs, and 2.6 times that of another foreign GAC-B. The equilibrium study of competitive adsorption between dichloroacetic acid and trichloroacetic acid on GAC-A demonstrates that the relative adsorption capacity of HAAs has a linear increase with their relative equilibrium concentration. The adsorption capacity for trichloroacetic acid is sensitive to changes at its equilibrium concentration greater than that for dichloroacetic acid.
