RESUMO
Cadmium (Cd) is a common heavy metal contamination that is highly toxic to liver. Puerarin (PU), a potent free radical scavenger, has been shown to exert cytoprotective effect in numerous pathological processes. However, whether PU affords protection against Cd-induced hepatotoxicity remains unclear to be known. Here, we aimed to investigate the protective effect of PU on Cd-induced hepatotoxicity in an immortalized mouse hepatocyte line, AML-12. First, Cd-induced cytotoxicity in AML-12 cells was obviously ameliorated by PU treatment. Also, Cd-induced apoptotic cell death was markedly alleviated by PU treatment, evidenced by two methods. Simultaneously, Cd-elevated malondialdehyde and reactive oxygen species levels were significantly reduced by PU administration, demonstrating the antioxidant effect of PU against Cd exposure. Moreover, Cd-induced blockage of autophagic flux in AML-12 cells was obviously restored by PU treatment, evidenced by immunoblot analysis of autophagy marker proteins and tandem fluorescent-tagged LC3 method. Resultantly, Cd-induced autophagosome accumulation was significantly alleviated by PU treatment. In conclusion, these observations demonstrate that PU treatment alleviates Cd-induced hepatic cell damage by inhibiting apoptosis and restoring autophagy activity, which is intimately related with its antioxidant activity.
Assuntos
Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Cádmio/toxicidade , Sequestradores de Radicais Livres/farmacologia , Hepatócitos/efeitos dos fármacos , Isoflavonas/farmacologia , Animais , Autofagossomos/efeitos dos fármacos , Autofagossomos/metabolismo , Autofagossomos/patologia , Biomarcadores/metabolismo , Técnicas de Cultura de Células , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Hepatócitos/metabolismo , Hepatócitos/patologia , Peroxidação de Lipídeos/efeitos dos fármacos , Camundongos , Estresse Oxidativo/efeitos dos fármacosRESUMO
OBJECTIVE: To research the effects and mechanism of Shenqi compound (SQC) on PTEN/ PI3K signal transducing path and angiogenesis in Goto-Kakizaki (GK) rats with diabetes mellitus type 2 (DM2) caused macroangiopathy. METHOD: GK rats with blood sugar > or = 11.1 mmol/L were divided into 4 groups, the GK group, the model group, the Western medicine (WM) group treated by atorvastatin 1.5 mg/(kg x d) and the Chinese medicine (CM) group treated with SQC 1.44 g/(kg x d). All were fed 35 days with high fatty diet, but to the latter three groups, N omega-nitriyl-L-arginine methyl ester 0.1 mg/mL was added into their drinking water for macroangiopathy model establishing. Besides, a group of normal Wistar rats fed with ordinary forage was set for control. Rat's blood glucose and lipids were measured, morphology of abdominal aorta wall tissue was observed with HE staining, and mRNA expressions of PTEN and PI3Kp85 in aortic wall were detected by Real-time PCR. RESULTS: General condition, gluco-lipid metabolism and aortic morphology in the CM group were significantly better than those in the model group. PTEN mRNA expression in the CM group (1.10 +/- 0.48) was significantly higher than that in the GK group (0.63 +/- 0.16) and the model group (0.17 +/- 0.07, both P < 0.01), but near to that in the WM group (1.11 +/- 0.46), while the PI3Kp85 mRNA expression in the TCM group (0.19 +/- 0.05) was lower than that in the GK group (1.38 +/- 0.43, P < 0.01), but near to that in the model group (0.33 +/- 0.09) and the WM group (0.11 +/- 0.06, both P > 0.05). CONCLUSION: SQC could increase the PTEN mRNA expression and restrain the PI3Kp85 mRNA expression in aorta, which is possibly the partial mechanisms of action of the remedy in inhibiting angiogenesis and preventing diabetic macroangiopathy.
Assuntos
Aterosclerose/prevenção & controle , Classe Ia de Fosfatidilinositol 3-Quinase/metabolismo , Angiopatias Diabéticas/tratamento farmacológico , Medicamentos de Ervas Chinesas/farmacologia , PTEN Fosfo-Hidrolase/metabolismo , Inibidores da Angiogênese/farmacologia , Inibidores da Angiogênese/uso terapêutico , Animais , Aorta/metabolismo , Astragalus propinquus/química , Classe Ia de Fosfatidilinositol 3-Quinase/genética , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/uso terapêutico , Masculino , PTEN Fosfo-Hidrolase/genética , Panax/química , Fitoterapia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos , Ratos Endogâmicos , Ratos Wistar , Transdução de Sinais/efeitos dos fármacosRESUMO
OBJECTIVE: To explore the effects and mechanism of ShenQi Compound Recipe on inflammation maker of type 2 diabetes mellitus in GK rats. METHODS: Rats were ranodmly divided into Model group, Ramipril group (positive control, 1 mg/kg x d), SQCR low dosage (0.72 g/kg x d), SQCR high dosage group (2.88 g/kg x d) and Wistar control group. Each group was administrated correspondent substance respectively for 32 days. Determined C-reactive protein (CRP) by ELISA and tumour necrosis factor (TNF)-alpha by radioimmunassay. The mRNA expression of nuclear factor (NF)-kappaB p65 in aorta was determined by real time RT-PCR, and activation of it using immunohistochemistry staining. RESULTS: Concentrations of CRP and TNF-alpha in serum and the expression of mRNA and activation of NF-kappaB were all decreased in SQCR low and high dosage groups compared with model group (P < 0.05 or P < 0.01). CONCLUSION: These results suggest that SQCR can decrease the level of inflammation maker in serum, which may be resulted from reducing the mRNA expression and activation of NF-kappaB.