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FEBS Open Bio ; 11(11): 2966-2976, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34407320


Myocardial infarction (MI) is caused by the formation of plaques in the arterial walls, leading to a decrease of blood flow to the heart and myocardium injury as a result of hypoxia. Ferroptosis is a crucial event in myocardial injury, and icariin (ICA) exerts protective effects against myocardial injury. Here, we investigated the protective mechanism of ICA in hypoxia/reoxygenation (H/R)-induced ferroptosis of cardiomyocytes. H9C2 cells were subjected to H/R induction. The content of lactate dehydrogenase and the levels of oxidative stress and intracellular ferrous ion Fe2+ were measured. The levels of ferroptosis markers (ACSL4 and GPX4) were detected. H/R-induced H9C2 cells were cultured with ICA in the presence or absence of ferroptosis inducer (erastin). Znpp (an HO-1 inhibitor) was added to ICA-treated H/R cells to verify the role of the Nrf2/HO-1 pathway. H/R-induced H9C2 cells showed reduced viability, enhanced oxidative stress and lactate dehydrogenase content, increased levels of Fe2+ and ACSL4, and decreased levels of GPX4. ICA inhibited H/R-induced ferroptosis and oxidative stress in cardiomyocytes. Erastin treatment reversed the inhibitory effect of ICA on ferroptosis in H/R cells. The expression of Nrf2 and HO-1 in H/R-induced H9C2 cells was reduced, whereas ICA treatment reversed this trend. Inhibition of the Nrf2/HO-1 pathway reversed the protective effect of ICA on H/R-induced ferroptosis. Collectively, our results suggest that ICA attenuates H/R-induced ferroptosis of cardiomyocytes by activating the Nrf2/HO-1 signaling pathway.

Hipóxia Celular/fisiologia , Flavonoides/farmacologia , Fator 2 Relacionado a NF-E2/metabolismo , Apoptose/efeitos dos fármacos , Hipóxia Celular/efeitos dos fármacos , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Ferroptose , Flavonoides/metabolismo , Hipóxia/tratamento farmacológico , Hipóxia/metabolismo , Traumatismo por Reperfusão Miocárdica/metabolismo , Miócitos Cardíacos/efeitos dos fármacos , Fator 2 Relacionado a NF-E2/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacos
Int J Colorectal Dis ; 31(2): 393-402, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26614505


PURPOSE: Surgical site infections (SSIs) following colorectal surgery is common, and local application of gentamicin for SSIs in the surgery remains controversial. OBJECTIVE: To identify whether local application of gentamicin reduces incidence of SSIs in colorectal surgery. METHODS: PubMed, Embase, the Cochrane Library, and Science Citation Index were searched for relevant randomized controlled trials (RCTs) and reference list up to November 2014. Two independent reviewers screened the records from the electronic databases, selected relevant studies, assessed the methodological quality, and extracted the data from included articles. Stata 12.0 was used to conduct a pooled analysis for main outcomes. RESULTS: Eight relevant randomized controlled trials with a total of 1685 patients were included in the meta-analysis. All included studies were of moderate to high quality by the Cochrane Collaboration's tool for assessing risk of bias. There was no significant difference being found in the total pooled results for wound infection (relative risk (RR) 0.73, 95% confidence interval (CI) 0.47 to 1.12) and organ space infection (RR 0.90, 95% CI 0.51 to 1.59). However, subgroup analysis showed that the significant decrease of wound infection was associated with the population in the Western Europe (RR 0.60, 95% CI 0.42 to 0.87) and follow-up periods of 30 days (RR 0.63, 95% CI 0.42 to 0.94). CONCLUSIONS: Local application of gentamicin significantly reduced incidence of wound infection following colorectal surgery in Western Europe, and it was also associated with lower risk of wound infection during follow-up period of 30 days. However, its effectiveness on prophylaxis of perineal wound infection and organ space infection still lacked evidence.

Antibacterianos/uso terapêutico , Doenças do Colo/cirurgia , Gentamicinas/uso terapêutico , Doenças Retais/cirurgia , Infecção da Ferida Cirúrgica/prevenção & controle , Administração Tópica , Neoplasias Colorretais/cirurgia , Humanos