Paraquat (PQ) intoxication causes thousands of mortalities every year, worldwide. Its pulmonary-targeted accumulation and the acute lung injury it subsequently causes, remain a challenge for detoxification treatment. A previous study has demonstrated that the upregulation of nuclear factor erythroid-2 related factor 2 (Nrf2) prevents PQ toxicity in cell line and murine models. As Nrf2 target genes include a group of membrane transporters, the current study assessed the protective mechanism exerted by Nrf2 against PQ toxicity and intracellular PQ accumulation via its effects on P-glycoprotein (P-gp), a downstream transporter of Nrf2. Adenovirus vectors containing the Nrf2 gene were transfected into A549 cells. Cell proliferation was assessed by Cell Counting Kit-8. The levels of LDH, MDA, SOD, TNF-α, IL-6 levels were detected using their respective ELISA kits. In addition, the levels of Nrf2 and P-gp protein expression were detected by western blot analysis. The concentration of PQ was measured by HPLC. The results revealed that overexpressed Nrf2 significantly increased P-gp protein levels, decreased the intracellular accumulation of PQ and attenuated PQ-induced toxicity. However, the protective effects of Nrf2 overexpression on PQ-challenged A549 cells were abrogated following cyclosporine A treatment, a competitive inhibitor of P-gp, which also increased intracellular PQ levels. These data indicated that Nrf2 gene overexpression prevented PQ toxicity in A549 cells, potentially via the upregulation of P-gp activity and the inhibition of intracellular PQ accumulation. Thus, Nrf2 and P-gp may serve as potential therapeutic targets for the treatment of PQ-induced injury.
In order to systematically evaluate the clinical efficacy and safety of misoprostol versus oxytocin in the prevention of postpartum hemorrhage, this paper provides evidence-based reference for clinical medication, computerized retrieval of Chinese biomedical literature database (CBM), PubMed, Embase, Cochrane Library, and clinical trials. The retrieval period is from the establishment of each database to October 1, 2021. Published randomized controlled trials (RCTS) are included in this study. The literature is screened and evaluated according to inclusion and exclusion criteria, and meta-analysis is performed using RevMan 5.3 software. A total of 13 RCTS are included, with a total of 24754 parturients. The meta-analysis shows the average blood loss (SMD = 0.10, 95% CI (−0.11, 0.32), P = 0.35 ), the time of the third stage of labor (SMD = 0, 95% CI (−0.07, 0.08), P = 0.95 ), and blood transfusion rate (RR = 0.80, 95% CI (0.63, 1.02), P = 0.07 ). However, the incidences of shivering (RR = 2.61, 95% CI (1.79, 0.81), P < 0.00001 ) and vomiting (RR = 2.78, 95% CI (1.85, 4.18), P < 0.00001 ) are significantly higher than those in oxytocin group. The effect of misoprostol on preventing postpartum hemorrhage is similar to that of oxytocin, but the incidence of adverse reactions is high, and the occurrence of adverse reactions should be closely watched in the use process. Due to the limitations of the included studies, multicenter, large-sample, and high-quality RCTS are still needed in the future to further verify this conclusion.
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