ABSTRACT
OBJECTIVES: Oxidative stress plays a major role in endothelial dysfunction. Citral is a monoterpene aldehyde with antioxidant properties. This study aimed to investigate the effect of citral on human umbilical vein endothelial cells (HUVECs) under hydrogen peroxide (H2O2)-induced oxidative stress. MATERIALS AND METHODS: The cells were treated with citral (0.625-10 µg/mL) for 24 h before exposure to H2O2 (0.5 mM, 2 h). Cell viability was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) assay. The hydroperoxide concentrations and ferric reducing ability of plasma (FRAP) were measured in intra- and extracellular fluids. RESULTS: Pretreatment of HUVECs with citral at concentrations of 5 and 10 µg/mL significantly enhanced the cell viability in H2O2-induced cytotoxicity. It reduced intracellular hydroperoxide levels at the concentrations of 5 and 10 µg/mL and extracellular hydroperoxide levels at the concentrations of 2.5-10 µg/mL. Pretreatment with citral significantly increased the FRAP value in intra- and extracellular fluids at the concentration range of 1.25-10 µg/mL. CONCLUSION: Antioxidant and cytoprotective effects were found for citral against oxidative damage induced by H2O2 in human endothelial cells. However, more studies in this area are needed to assess its clinical value for prevention and treatment of cardiovascular diseases.
ABSTRACT
PURPOSE: Sal-like protein 4 transcription factor (SALL4) is a stem cell transcription factor that plays an essential role in the maintenance and self-renewal of embryonic and hematopoietic stem cells, functioning as an oncogene in several cancers. However, the role of SALL4 in the biological behavior of childhood acute lymphoblastic leukemia and its relationship with multidrug resistance and relapse has remained largely unknown. PATIENTS AND METHODS: Quantitative real-time polymerase chain reaction (qRT-PCR) was used to characterize the expression pattern of SALL4 in the bone marrow samples of 43 patients with Philadelphia negative ALL and 18 children in the non-cancer control group. The presence of minimal residual disease was measured a year after the initial therapy using SSCP (single-strand conformation polymorphism). In addition, the correlation between the expression of SALL4 and ABCA3 in relapsed patients was analyzed statistically. RESULTS: Results showed an overexpression of SALL4 in de novo patients compared with the control group (P=0.0001, AUC= 0.93), indicating the importance of this gene in the induction of leukemia. A significant increase in the ABCA3 expression levels was revealed in the relapsed patients, in comparison with the drug-sensitive group (P = 0.0005). The leukemogenetic effect of SALL4 can be related to the effect of this gene on the maintenance of pluripotency in cancer stem cells. Results also suggest that the expression of SALL4 can be considered as a diagnostic marker for pediatric ALL. Moreover, SALL4 expression levels in the minimal residual disease positive (mrd+) ALL group was significantly higher than those in the mrd- group (p=0.0001, AUC= 0.92). CONCLUSION: These data demonstrate the prognostic impact of SALL4 in childhood ALL. Our findings also indicated a direct correlation between the mRNA expression levels of SALL4 and ABCA3 transporter in the relapsed group of ALL patients (r=0.7). These results describe a possible mechanism by which SALL4 may lead to the development of multidrug resistance.
