RESUMO
OBJECTIVES: Nardostachys jatamansi belonging to the family Valerianaceae has been used as a remedy for stomach and skin ailments in Korea. The effect of N. jatamansi on acute pancreatitis (AP) has not been defined. Therefore, we investigated the effect of N. jatamansi on cerulein-induced AP. METHODS: In the pretreatment group, N. jatamansi was administered orally to mice at 10 and 20 mg/kg for 5 days, and the mice were intraperitoneally injected with the stable cholecystokinin analogue cerulein hourly for 6 hours. In the posttreatment group, cerulein was injected hourly for 6 hours, and N. jatamansi was administered at the indicated time (1, 3, and 5 hours after the first cerulein injection) and dose (10 and 20 mg/kg) during the cerulein injection. Blood samples were taken 6 hours later to determine the serum amylase, the lipase, and the cytokine levels. The pancreas and the lung were rapidly removed for morphologic examination, myeloperoxidase assay, and real-time reverse transcription polymerase chain reaction. RESULTS: Nardostachys jatamansi treatment attenuated the AP, as shown by the histological examination results of the pancreas and the lung, reductions in pancreatic edema, neutrophil infiltration, serum amylase and lipase levels, serum cytokine levels, and messenger RNA expressions of inflammatory mediators. CONCLUSIONS: These results suggest that N. jatamansi attenuates the severity of AP and pancreatitis-associated lung injury.
Assuntos
Nardostachys/química , Pâncreas/efeitos dos fármacos , Pancreatite/prevenção & controle , Extratos Vegetais/farmacologia , Doença Aguda , Amilases/sangue , Animais , Peso Corporal/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Ceruletídeo , Citocinas/sangue , Citocinas/genética , Ativação Enzimática/efeitos dos fármacos , Ensaio de Imunoadsorção Enzimática , Feminino , Lipase/sangue , Camundongos , Camundongos Endogâmicos C57BL , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Tamanho do Órgão/efeitos dos fármacos , Pâncreas/metabolismo , Pâncreas/patologia , Pancreatite/sangue , Pancreatite/induzido quimicamente , Peroxidase/metabolismo , Fitoterapia , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
Glycogen synthase kinase-3 (GSK-3) plays an important role in the regulation of apoptosis. However, the role of GSK-3 in the auditory system remains unknown. Here we examined whether the GSK-3-specific inhibitors, SB 216763 and LiCl, could protect against cisplatin-induced cytotoxicity of auditory cells. GSK-3 was activated by cisplatin treatment of HEI-OC1 cells. SB 216763 or LiCl treatments inhibited cisplatin-induced apoptosis in a dose-dependent manner and activated caspase-9, -8 and -3. In rat primary explants of the organ of Corti, SB 216763 or LiCl treatments completely abrogated the cisplatin-induced destruction of outer hair cell arrays. Administration of SB 216763 or LiCl inhibited cochlear destruction and the production of tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta) and IL-6 in cisplatin-injected mice. Furthermore, administration of SB 216763 or LiCl reduced the thresholds of the auditory brainstem response (ABR) in cisplatin-injected mice. Collectively, these results suggest that cisplatin-induced ototoxicity might be associated with modulation of GSK-3 activation.
Assuntos
Antineoplásicos/toxicidade , Cisplatino/toxicidade , Quinase 3 da Glicogênio Sintase/antagonistas & inibidores , Perda Auditiva/prevenção & controle , Indóis/farmacologia , Cloreto de Lítio/farmacologia , Maleimidas/farmacologia , Órgão Espiral/efeitos dos fármacos , Inibidores de Proteínas Quinases/farmacologia , Estimulação Acústica , Animais , Antineoplásicos/administração & dosagem , Apoptose/efeitos dos fármacos , Caspases/metabolismo , Linhagem Celular , Cisplatino/administração & dosagem , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Ativação Enzimática , Potenciais Evocados Auditivos do Tronco Encefálico/efeitos dos fármacos , Quinase 3 da Glicogênio Sintase/metabolismo , Glicogênio Sintase Quinase 3 beta , Células Ciliadas Auditivas/efeitos dos fármacos , Células Ciliadas Auditivas/enzimologia , Perda Auditiva/induzido quimicamente , Perda Auditiva/enzimologia , Perda Auditiva/patologia , Perda Auditiva/fisiopatologia , Indóis/administração & dosagem , Injeções Intraperitoneais , Interleucina-1beta/sangue , Interleucina-6/sangue , Cloreto de Lítio/administração & dosagem , Maleimidas/administração & dosagem , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Técnicas de Cultura de Órgãos , Órgão Espiral/enzimologia , Órgão Espiral/patologia , Órgão Espiral/fisiopatologia , Fosforilação , Ratos , Ratos Sprague-Dawley , Fatores de Tempo , Fator de Necrose Tumoral alfa/sangueRESUMO
AIM: To investigate the effect of Gardenia jasminoides (GJ) on cerulein-induced acute pancreatitis (AP) in mice. METHODS: C57BL/6 mice weighing 18-20 g were divided into three groups. (1) Normal saline-treated group, (2) treatment with GJ at a dose of 0.1 g/kg, (3) treatment with GJ at a dose of 1 g/kg. GJ was administered orally (n = 6 per group) for 1 wk. Three hours later, the mice were given an intraperitoneal injection of cerulein (50 microg/kg), a stable cholecystokinin (CCK) analogue, every hour for a total of 6 h as described previously. The mice were sacrificed at 6 h after completion of cerulein injections. Blood samples were obtained to determine serum amylase, lipase and cytokine levels. The pancreas was rapidly removed for morphologic examination and scoring. A portion of pancreas was stored at -70 degree and prepared for the measurement of tissue myeloperoxidase (MPO) activity, an indicator of neutrophil sequestration, and for reverse-transcriptase PCR (RT-PCR) and real-time PCR measurements. RESULTS: Treatment with GJ decreased significantly the severity of pancreatitis and pancreatitis-associated lung injury. Treatment with GJ attenuated the severity of AP compared with saline-treated mice, as shown by reduction in pancreatic edema, neutrophil infiltration, serum amylase and lipase levels, serum cytokine levels, and mRNA expression of multiple inflammatory mediators. CONCLUSION: These results suggest that GJ attenuated the severity of AP as well as pancreatitis-associated lung injury.