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 To detect the transcription factors of copper ion (Cu,2+) metabolism and oxidative stress by Candida albicans knocked down different transcription factors.Methods Spot assay, growth curve were used.Results The sensitivity to Cu,2+ in Cup2Δ/Δ was increasing and the growth of Cup2Δ/Δ was inhibited in 5 mmol /L Cu,2+ medium.The results showed that Cup2Δ/Δ also increased the sensitivity to H2O2, interestingly, Cu,2+and H2O2 played a synergistic antifungal effect.The tolerance of Cup2Δ/Δ and SN250 to H2O2 induced oxidative stress was increased after BCS chelating Cu,2+.In the fluconazole, miconazole and ketoconazole susceptibility experiments, Cup2Δ/Δ did not show susceptibility to azole drugs.Conclusion Knockout transcription factor Cup2, which could increase the sensitivity to Cu,2+ and H2O2in Candida albicans.Transcription factor Cup2 might be involved in the regulation and control of Candida albicansmetabolism on Cu,2+ and oxidative stress induced by H2O2, but not involved in the regulation and control of drug resistance to azole drugs.