Ted to a decrease in defense against apoptosis [32]. Elevated vWF expression in pregnant girls with PE, when in comparison to wholesome pregnant women, was associated with platelet activation [35]. Our information suggest that endothelial cells exposed to plasma from pregnant females with PE upregulate these biomarkers, and additional turn into dysfunctional. As eNOS quantification was not the aim of our study, we only made use of a pharmacological tool to inhibit eNOS activity. In addition, the outcomes on eNOS protein levels in preeclampsia are controversial. Though some authors found reduced concentrations of eNOS in preeclampsia, other folks showed an increase or undetectable levels. To our expertise, only one study has evaluated eNOS levels in this model, and no distinction was observed involving endothelial cells treated with plasma from preeclamptic pregnant or healthful pregnant women [14,368]. Hence, quantification of eNOS protein may not be a good indicator of eNOS pathway activation within this in vitro model. Thus, for treatment and/management of this syndrome, study has focused on antioxidant compounds. Trans-resveratrol (RSV) is an antioxidant with significant effects around the pathophysiology of PE [39]. Our data showed an increase in NO bioavailability and decrease in arginase activity. These results corroborate earlier information demonstrating that RSV enhances NO production by means of many mechanisms, which include eNOS activation/expression [18]. The modulatory action on arginase may be because of the presence of a catechol group inside the chemical structure of resveratrol, which could improve its inhibitory activity [40]. Moreover, RSV therapy alone didn’t alter ROS levels. However, when combined with L-NAME or apocynin, ROS levels were decreased, suggesting that eNOS and NOX will be the key producers of ROS, as hypothesized above. Interestingly, even with no modifications in ROS levels, our data demonstrated that the cells treated with plasma and RSV showed a larger total antioxidant capacity than the PE plasma with no treatment.RS 09 Purity These final results corroborate previous data showing that RSV is really a ROS scavenger [41].Crystal Violet Biological Activity Nevertheless,Antioxidants 2022, 11,10 ofwe showed that RSV incubation downregulates endothelial dysfunction genes which include ICAM-1, vWF, and CASP-3 in endothelial cells and umbilical arteries of patients with PE.PMID:27017949 These information corroborate with preceding studies showing that RSV acts by decreasing these genes [424]. five. Conclusions Our information suggest that RSV treatment increases NO bioavailability and decreases arginase activity, ROS production combined with enzyme inhibitors, and endothelial dysfunction genes in endothelial cells incubated with plasma from patients with PE and umbilical arteries from PE sufferers. Additional understanding of RSV modulatory actions within the L -arginine O pathway working with our model can let, within the future, the improvement of a treatment for this illness.Author Contributions: Conceptualization, T.O.B.-P. and V.C.S.; sample choice and collection, T.O.B.-P., R.C.C., J.F.A. and G.M.Z.; methodology, T.O.B.-P., M.B.-M., P.R.N. and G.M.Z.; analysis, T.O.B.-P.; resources, V.C.S.; writing–original draft preparation, T.O.B.-P. and V.C.S.; supervision, V.C.S. All authors have study and agreed towards the published version from the manuscript. Funding: This study was funded by Funda o de Amparo Pesquisa do Estado de S Paulo (FAPESP), grants: 2021/01945-5; 2020/14610-9; 2019/07230-8 and Conselho Nacional de Desenvolvimento Cient ico e Tecnol ico (CNPq), Grant: 133901/2021-1.
