ABSTRACT
Objective To explore the effects of Toddalia asiatica extract( TAE) on oxidative damages in mice with myocardial ischemia and hyperlipidemia. Methods Fifty SPF male KM mice were randomly divided into 5 groups:control group,model group,simvastatin group (5 mg/kg),high-dose TAE group (400 mg/kg) and low-dose TAE group (100 mg/kg) . Hyperlipidemia was induced by feeding milk for 4 weeks. At the same time,the corresponding drug was given by oral administration with 20 mL/kg for 28 d. At the end of four-week treatment, isoprenaline hydrochloride ( Iso ) was subcutaneously injected every 24 hours for three times. The body weight, electrocardiogram, heart and liver indexes, myocardial water content, and the serum levels of TC, TG, HDL, LDL, SOD, MDA and GPx were measured. Results TAE significantly improved the electrocardiogram changes induced by Iso and milk in the mice, weight lose, inhibited the heart and liver indexes, reduced the myocardial water content, decreased the levels of TC, TG, LDL and MDA, and increased the contents of HDL, SOD and GPx. Conclusions TAE may play an important role in cardiovascular protection by regulating oxygen free radical metabolism and improving oxidative damages.
ABSTRACT
5-fluorouracil (5-FU) is a chemotherapeutic agent commonly used for treatment of solid tumors, including colorectal cancer. However, chemoresistance against 5-fluorouracil (5-FU) often limits its success for chemotherapy and, therefore, finding out appropriate adjuvant(s) that might overcome chemoresistance against 5-FU bears a significant importance. In the present study, we have found that α-mangostin can sensitize 5-FU-resistant SNUC5/5-FUR colon cancer cells to apoptosis. Exposure of α-mangostin induced significant DNA damages and increased the intracellular 8-hydroxyguanosine (8-OH-G) and 4-hydroxynonenal (4-HNE) levels in SNUC5 and SNUC5/5-FUR cells. Western blot analysis illustrated that α-mangostin-induced apoptosis was mediated by the activation of the extrinsic and intrinsic pathways in SNUC5/5-FUR cells. In particular, we observed that Fas receptor (FasR) level was lower in SNUC5/5-FUR cells, compared with SNUC5 cells and that silencing FasR attenuated α-mangostin-mediated apoptosis in SNUC5/5-FUR cells. Together, our study illustrates that α-mangostin might be an efficient apoptosis sensitizer that can overcome chemoresistance against 5-FU by activating apoptosis pathway.
Subject(s)
fas Receptor , Apoptosis , Blotting, Western , Colon , Colonic Neoplasms , Colorectal Neoplasms , DNA Damage , Drug Therapy , FluorouracilABSTRACT
The present study investigated the role of selenium (Se) in regulating cadmium (Cd)-induced oxidative stress in sunflower (Helianthus annuus) roots. Short-term exposure of plants to 20 μM Cd intensively increased hydrogen peroxides (H2O2), protein carbonyl (PCO) content and lipid peroxidation as indicated by malondialdehyde (MDA) accumulation. In contrast, Se (5, 10 and 20 μM) pretreatment alleviated the oxidative damages as evidenced by the lowered H2O2, protein carbonyl (PCO) and MDA content. Concomitantly, Se treatment enhanced the activities of catalase (CAT, EC 1.11.1.6), ascorbate peroxidase (APX, EC 1.11.1.11) and glutathione peroxidase (GPX, EC 1.11.1.9), but lowered that of superoxide dismutase (SOD, EC 1.15.1.1) in the root exposed Cd. Taken together, our results strongly suggest that exogenous Se may improve the tolerance of the plant to the Cd-induced oxidative stress.
ABSTRACT
Objective To investigate the mechanism of malignant transformation in human bronchial epithelial cell line BEP2D exposed to α-particles.Methods The levels of intracellular ROS and malonaldehyde (MDA) in BEP2D,RH22 (passage 22 of α-particle-irradiated BEP2D cells) and BERP35T-1 cells (derived from nude mice bearing malignant transformed cells generated from the passage 35 of α-particle-irradiated BEP2D cells) were assayed with DCFH-DA and MDA kit,respectively.The expressions of 8-OH-dG and γ-H2AX in BEP2D,RH23 (passage 23 of α-particle-irradiated BEP2D cells)and BERP35T-1 cells were also measured with immunocytochemistry and immunofluorescence staining.Results Compared to BEP2D cells,the levels of ROS ( t =4.30 and 3.94,P ＜ 0.05 ) and MDA ( t =4.89 and 15.10,P ＜0.05) increased in RH22 and BERP35T-1 cells.The expressions of 8-OH-dG (t =3.80 and 2.92,P ＜ 0.05 ) and γ-H2AX ( t =7.61 and 12.67,P ＜ 0.05 ) in RH23 and BERP35T-1 cells were also higher than those in BEP2D cells.Conclusions Oxidative stress induces lipid peroxidation and DNA damage leading to genomic instability,which could contribute to cellular malignant transforming process in the human bronchial epithelial cell line BEP2D with α-particle exposure.