ABSTRACT
Objective@#To investigate the protective effect of oligomeric proanthocyanidins (OPCs) in paraquat-exposed mice.@*Methods@#An acute lung injury model was established by a single intraperitoneal injection of paraquat (PQ) in BALB/c mice. The mice were randomized into control group, paraquat-exposed group (PQ group) , oligomeric proanthocyanidins group (OPCs group) , and paraquat and oligomeric proanthocyanidins-exposed group (PQ+OPCs group) , with 10 mice in each group. Only normal saline was intraperitoneally injected into the mice in the control group. The mice in the PQ group were divided into 8 subgroups according to the dose of poison administered, i.e., 0, 25, 50, 75, 100, 150, 200, and 300 mg/kg; the mice in each subgroup were given a single intraperitoneal injection of PQ and were observed and recorded for death at 3, 6, 12, 24, 36, 48, 60, 84, and 96 hours after PQ injection. Origin 8.0 was used to calculate the median lethal dose (LD50) of the mice at 24, 36, 48, and 60 hours after PQ injection, and the PQ dose (100 mg/kg, ip) was chosen based on the accumulated mortality rate. An OPCs-treated experimental model was established by an intraperitoneal injection of OPCs followed by a single PQ injection (100 mg/kg, ip) 1 hour later to observe the effects of OPCs on the apparent poisoning effect and fatality rate in PQ-induced mice. Immunohistochemistry was used to determine the effect of OPCs on PQ-induced lung tissue lesions. The peripheral blood samples of the mice were collected to determine the effects of OPCs on PQ-induced inflammatory factors such as tumor necrosis factor-α (TNF-α) , interleukine-1β (IL-1β) , and transforming growth factor-β1 (TGF-β1) using enzyme-linked immunosorbent assay.@*Results@#The mortality rate was significantly correlated with the dose and exposure time in PQ-exposed mice; the mortality rate gradually increased with increasing dose and exposure time of the poison (P<0.05) . The LD50 values for the mice were 216.67, 124.11, and 71.24 mg/kg at 24, 48, and 72 hours after PQ exposure, respectively. PQ could induce animal death at 12 hours after injection, and the mortality rate of the animals was 40% (4/10) at 48 hours after PQ exposure. The PQ-induced mortality rate of the mice in the PQ+OPCs group was reduced, and the mortality rate of the animals was 10% (1/10) at 48 hours after PQ exposure. Compared with treatment in the control group, OPCs exposure alone had no significant effect on the expression of TNF-α and TGF-β1 in the peripheral blood (P>0.05) , but it significantly inhibited the expression of IL-1β (P<0.05) . After 48 hours, the expression of TNF-α, TGF-β1, and IL-1β in peripheral blood significantly increased by 39%, 45%, and 38%, respectively, in the PQ group (P<0.05) , but they significantly decreased by 31%, 13%, and 22%, respectively, in the OPCs+PQ group as compared with the PQ group (P<0.05) .@*Conclusion@#OPCs pretreatment can significantly alleviate PQ-induced poisoning effect.
ABSTRACT
Objective@#The present study was designed to evaluate the protective effects of oligomeric proanthocyanidins (OPC) in mice exposed to paraquat (PQ) , and to explore the molecular mechanism.@*Methods@#Four experimental groups were designed. Control group: 10 BALB/c mice were intraperitoneally injected with normal saline) . PQ group: 10 BALB/c mice were intraperitoneally injected with PQ (100 mg/kg) . PQ+OPC group: 10 BALB/c mice were administered with OPC (100 mg/kg) for 1 h before PQ (100 mg/kg) expo-sure. OPC group: 10 BALB/c mice were intraperitoneally injected with OPC (100 mg/kg) . The peripheral blood samples or lung tissue samples were collected at the designed time points for measuring the levels of oxi-dative stress indicators, the related protein levels of nuclear factor-kappa B (NF-κB) pathway and nuclear fac-tor erythroid related factor-2 (Nrf2) pathway.@*Results@#Compared with the control group, the level of reactive oxygen species (ROS) , the content of malondialdehyde (MDA) in the PQ group were significantly induced, and the activity of superoxide dismutase (SOD) in the PQ group was decreased in the peripheral blood. As com-pared with the PQ group, the level of ROS and the content of MDA in the PQ+OPC group were significantly re-duced, the activity SOD in the PQ+OPC group was increased in the peripheral blood; the level of ROS and the content of MDA were also reduced in lung tissues in the PQ+OPC group. Moreover, compared with the con-trol group, the phosphorylation of IκBα and the expression of NF-κB p65 were increased in lung tissues in the PQ group. The phosphorylation of IκBα and the expression of NF-κB p65 were decreased in lung tissues in the PQ+OPC group as compared with the PQ group. In addition, compared with the control group, the expressions of HO-1 and Nrf2 were increased in lung tissues in OPC group, and these were decreased in lung tissues in PQ groups. Furthermore, the expressions of HO-1 and Nrf2 were also increased in lung tissues in PQ+OPC as com-pared with the PQ group.@*Conclusion@#OPC could alleviate PQ-induced systemic toxicity in mice by regulating oxidative stress via NF-κB and Nrf2 pathway.
ABSTRACT
BACKGROUND:Normal stem cells and tumor stem cells have differences in cellsignaling pathway of gene expression and dependence. How to find a therapeutic method of selectively kil ing tumor stem cells is a topic that should be studied greatly. OBJECTIVE:To isolate human liver cancer stem cells MHCC97 and to investigate the biological characteristics of them. METHODS:Tumor stem cells were selected from highly metastatic human hepatoma cellline MHCC97 by flow cytometry. CD133-CD34-MHCC97 from normal human liver stem cells and CD133+CD34+MHCC97 from tumor stem cells were isolated. Their phenotypes, growth curve, cellcycle and multi-lineage differentiation were measured. RESULTS AND CONCLUSION:Phenotypes of CD133+CD34+MHCC97 cancer stem cells were CD133+and CD34+and they had the same growth curve and cellcycle with the liver stem cells CD133-CD34-MHCC97, besides, they had the differential ability to epithelial cells and endothelial cells that proved to be stem cells. These results indicated that human cancer stem cells CD133+CD34+MHCC97 had the specific characteristics of tumor stem cells, could differentiate into epithelial cells and endothelial cells, had the biological property of tumor stem cells, was an origin of tumor relapse and metastasis, and a target of clinical therapy.