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1.
Pharm Biol ; 59(1): 1286-1293, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34517734

RESUMO

CONTEXT: Rosmarinic acid (RA) dose-dependently ameliorates acetaminophen (APAP) induced hepatotoxicity in rats. However, whether RA hepatoprotective effect is by regulating RACK1 and its downstream signals is still unclear. OBJECTIVE: This study explores the RA protective effect on APAP-induced ALI and its mechanism. MATERIALS AND METHODS: Sixty Kunming mice 6-8 weeks old were randomly separated into six groups (n = 10) and pre-treated with normal saline, ammonium glycyrrhetate (AG) or RA (10, 20 or 40 mg/kg i.p./day) for two consecutive weeks. Then, APAP (300 mg/kg, i.g.) was administrated to induce ALI, except for the control. Serum alanine/aspartate aminotransferases (ALT and AST), malondialdehyde (MDA), superoxide dismutase (SOD) and histopathology were used to authenticate RA effect. The liver RACK1 and TNF-α were measured by western blot. RESULTS: Compared with the APAP group, different dosages RA significantly decreased ALT (52.09 ± 7.98, 55.13 ± 10.19, 65.08 ± 27.61 U/L, p < 0.05), AST (114.78 ± 19.87, 115.29 ± 31.91, 101.78 ± 21.85 U/L, p < 0.05), MDA (2.37 ± 0.87, 2.13 ± 0.87, 1.86 ± 0.39 nmol/mg, p < 0.01) and increased SOD (306.178 ± 90.80, 459.21 ± 58.54, 444.01 ± 78.09 U/mg, p < 0.05). With increasing doses of RA, RACK1 and TNF-α expression decreased. Moreover, the RACK1 and TNF-α levels were positively correlated with MDA (r = 0.8453 and r = 0.9391, p < 0.01). DISCUSSION AND CONCLUSIONS: Our findings support RA as a hepatoprotective agent to improve APAP-induced ALI and the antioxidant effect mediated through RACK1/TNF-α pathway.


Assuntos
Acetaminofen/toxicidade , Antioxidantes/farmacologia , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Cinamatos/farmacologia , Depsídeos/farmacologia , Animais , Animais não Endogâmicos , Antioxidantes/administração & dosagem , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Cinamatos/administração & dosagem , Depsídeos/administração & dosagem , Relação Dose-Resposta a Droga , Ácido Glicirretínico/análogos & derivados , Ácido Glicirretínico/farmacologia , Masculino , Malondialdeído/metabolismo , Camundongos , Receptores de Quinase C Ativada/metabolismo , Superóxido Dismutase/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Ácido Rosmarínico
2.
Cancer Manag Res ; 11: 8249-8255, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31571982

RESUMO

PURPOSE: The study aimed to explore the survival outcomes of early-stage cervical cancer (CC) patients treated with laparoscopic/abdominal radical hysterectomy (LRH/ARH). PATIENTS AND METHODS: We performed a retrospective analysis involving women who had undergone LRH/ARH for CC in early stage during the 2013-2015 period in West China Second University Hospital. The survival outcomes and potential prognostic factors were evaluated using Kaplan-Meier method and Cox regression analysis, respectively. RESULTS: A total of 678 patients were included in our analysis. The overall survival (OS) and progression-free survival (PFS) between the ARH (n=423) and LRH (n=255) groups achieved no significant differences (p=0.122, 0.285, respectively). However, in patients with a tumor diameter >4 cm, the OS of the LRH group was significantly shorter than that of the ARH group (p=0.017). Conversely, in patients with a tumor diameter ≤4 cm, the LRH group had a significantly longer OS than the ARH group (p=0.013). The multivariate Cox analysis revealed that International Federation of Gynecology and Obstetrics stage, histology, parametrial invasion, and pelvic lymph node invasion were independent prognostic factors for OS and PFS, whereas surgical method was not a statistically significant predictor of OS (p=0.806) or PFS (p=0.236) in CC patients. CONCLUSION: LRH was an alternative to ARH for surgical treatment of CC patients with a tumor diameter ≤4 cm. However, for the patients with a tumor diameter >4 cm, priority should be given to ARH.

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