Gestational Diabetes Mellitus: The Crosslink among Inflammation, Nitroxidative Stress, Intestinal Microbiota and Alternative Therapies.

Gestational diabetes mellitus (GDM) is characterized by a set of metabolic complications arising from adaptive failures to the pregnancy period. Estimates point to a prevalence of 3 to 15% of pregnancies. Its etiology includes intrinsic and extrinsic aspects of the progenitress, which may contribute to the pathophysiogenesis of GDM. Recently, researchers have identified that inflammation, oxidative stress, and the gut microbiota participate in the development of the disease, with potentially harmful effects on the health of the maternal-fetal binomial, in the short and long terms. In this context, alternative therapies were investigated from two perspectives: the modulation of the intestinal microbiota, with probiotics and prebiotics, and the use of natural products with antioxidant and anti-inflammatory properties, which may mitigate the endogenous processes of the GDM, favoring the health of the mother and her offspring, and in a future perspective, alleviating this critical public health problem.

The impact on colostrum oxidative stress, cytokines, and immune cells composition after SARS-CoV-2 infection during pregnancy.

Background: Limited data are available regarding the differences between immunological, biochemical, and cellular contents of human colostrum following maternal infection during pregnancy with coronavirus 2 disease (COVID-19). Objective: To investigate whether maternal COVID-19 infection may affect immunological, biochemical, and cellular contents of human colostrum. Methods: Using a case-control study design, we collected colostrum from 14 lactating women with a previous diagnosis of COVID-19 during pregnancy and 12 without a clear diagnosis during September 2020 to May 2021. Colostrum samples were analysed for some enzymes and non-enzymatic oxidative stress markers (SOD, CAT, GPx, MDA, GSH, GSSG, H2O2, MPO) and for IL-1ß, IL-6, tumour necrosis factor (TNF)-α, protein induced by interferon gamma (IP)-10, IL-8, IFN-λ1, IL12p70, IFN-α2, IFN-λ2/3, granulocyte macrophage colony stimulating factor (GM-CSF), IFN-ß, IL-10 and IFN-γ, along with IgA and IgG for the SARS-CoV-2 S protein. We perform immunophenotyping to assess the frequency of different cell types in the colostrum. Results: Colostrum from the COVID-19 symptomatic group in pregnancy contained reduced levels of H2O2, IFN-α2, and GM-CSF. This group had higher levels of GSH, and both NK cell subtypes CD3-CD56brightCD16-CD27+IFN-γ+ and CD3-CD56dimCD16+CD27- were also increased. Conclusion: The present results reinforce the protective role of colostrum even in the case of mild SARS-Cov-2 infection, in addition to demonstrating how adaptive the composition of colostrum is after infections. It also supports the recommendation to encourage lactating women to continue breastfeeding after COVID-19 illness.

Biomarkers of Inflammation and Redox Imbalance in Umbilical Cord in Pregnancies with and without Preeclampsia and Consequent Perinatal Outcomes.

OBJECTIVE: To compare redox imbalance and inflammation biomarkers in umbilical cords from pregnancies with and without preeclampsia (PE) and to analyse their relationships with perinatal outcomes. METHODS: A controlled cross-sectional study was conducted in Maceió, Alagoas, Brazil, that involved pregnant women with PE and a group of women without the disease, through the application of a standardized questionnaire. After delivery, umbilical cord samples were collected to measure antioxidant defense, products from oxidative damage, and inflammation biomarkers such as myeloperoxidase (MPO), interleukin- (IL-) 6, IL-8, IL-10, and tumor necrosis factor-alpha (TNF-α). Statistical analyses were performed using Stata version 13.0 software and IBM Statistical Package for the Social Sciences (SPSS) 20.0, adopting a 95% confidence level (α = 0.05), with the chi-square test, the Wilcoxon-Mann-Whitney test, and the multinomial and Poisson regression tests. RESULTS: One hundred PE pregnant women and 50 women without the disease were studied. The umbilical cords from PE pregnancies showed higher levels of reduced glutathione (GSH) (p ≤ 0.001), glutathione peroxidase (GPx) (p = 0.016), and malondialdehyde (MDA) (p = 0.028) and lower levels of IL-6 (p = 0.030) and TNF-α (p ≤ 0.001) than the other group, with some associations among these biomarkers with perinatal outcomes. CONCLUSION: The higher levels of GSH and GPx, in addition to the lower levels of IL-6 and TNF-α, found in the PE umbilical cord, may result from adaptive mechanisms to maintain the oxidative and inflammatory balance; however, despite these changes, the damage to the cell membranes was not minimized, as the MDA level was higher in women with PE than in women without the disease. This implies that a redox imbalance is present, confirming that other physiological and adaptive mechanisms are being activated to preserve foetal health. Therefore, the present work unveils an important role of the umbilical cord in controlling redox imbalance and inflammation in PE pregnancies. Our results reinforce the necessity for continuous research on GSH as a protective compound for the perinatal outcome, especially in PE women.

Oxidative stress markers in preeclamptic placentas: A systematic review with meta-analysis.

INTRODUCTION: Oxidative stress (OS) is the basis of several diseases. Preeclampsia (PE) is a multisystemic syndrome, considered one of the major causes of maternal and fetal mortality. The placenta is considered the main anatomical pathogenetic substrate for the disease, being the placental OS a likely critical pathway in the pathogenesis of PE. This meta-analysis aimed to verify whether there is OS in the preeclamptic placenta and which markers are altered in this condition. METHODS: The search was conducted in the following databases: MEDLINE (via PubMed), Lilacs and Scopus. Relevant studies were identified until May 2020. The quality of the studies was evaluated according to the Newcastle-Ottawa scale. RESULTS: From the 3998 screened records, 43 were finally included in the systematic review, and 23 in the meta-analysis. The biomarkers evaluated were related to cell and macromolecules' damage, such as malondialdehyde (MDA), 8-hydroxy-2'-deoxyguanosine (8-OH-dG), lipid peroxides, isoprostane, total oxidant status (TOS), carbonylated proteins and some of the reactive oxygen and nitrogen species (RONS), like hydrogen peroxide and nitric oxide. It was also related to antioxidant activity, both enzymatic, including superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx), glutathione S-transferase and total antioxidant status, and non-enzymatic, through quantification of reduced glutathione, vitamin C and E, zinc and copper. CONCLUSION: It was observed that there was OS in the preeclamptic placentas, based on results, like lower activity of some of the enzymes of the antioxidant system (SOD and GPx) as well as the increase in oxidative damage markers (MDA and lipid peroxide), corroborating literature data.

Pre-eclampsia is associated with later kidney chronic disease and end-stage renal disease: Systematic review and meta-analysis of observational studies.

OBJECTIVES: To assess whether there is a risk of kidney disease during the postpartum period of women who had preeclampsia (PE). STUDY DESIGN: Observational trials were searched in the PubMed, Science Direct, Clinical trials, Cochrane, LILACS and Web of Science databases. The data extracted from the studies were systematized, and the risk of bias was evaluated for each of them. Meta-analyses were performed with studies that evaluated chronic kidney disease (CKD) and end-stage renal disease (ESRD), pooling the natural logarithms of the adjusted risk measures and the confidence intervals of each study in a random effects model. RESULTS: Of the 4149 studies evaluated, 35 articles were included in the review, of which 3 of the CKD and 6 of the ESRD presented the necessary outcomes to compose the meta-analysis. A formal registration protocol was included in the PROSPERO database (number: CRD42019111821). There was a statistically significant difference between the development of CKD (hazard ratio (HR): 1.82, confidence interval to 95% (95% CI): 1.27-2.62, P < 0.01) and ESRD (HR: 3.01, confidence interval to 95% (95% CI): 1.92-4.70, P < 0.01) in postpartum women affected by PE. CONCLUSIONS: PE was considered a risk factor for the onset of CKD and ESRD in the postpartum period. Thus, more research is needed to clarify the underlying mechanisms of this association, and to assist in determining the most appropriate and effective clinical conduct to prevent and/or treat such complications.

Biomarkers of placental redox imbalance in pregnancies with preeclampsia and consequent perinatal outcomes.

OBJECTIVE: To compare redox and inflammatory markers between normal and PE-derived placentas and to evaluate the relationship between placental redox imbalance markers and perinatal outcomes in pregnancies with PE. METHODS: This was a cross-sectional study conducted at the maternity hospital of a university hospital in Maceio-Alagoas, Brazil, in 2017, including women diagnosed with PE and healthy pregnant women and their conceptuses. After screening, standardized questionnaires containing socioeconomic, clinical, obstetric and anthropometric data were applied. After delivery, placental samples were collected for quantification of biomarkers of redox imbalance (catalase - CAT; malondialdehyde - MDA; hydrogen peroxide - H2O2; superoxide dismutase - SOD; reduced glutathione - GSH; oxidized glutathione - GSSG; and their ratio - GSH/GSSG) and inflammation (myeloperoxidase - MPO; interleukin (IL)-6; IL-8; IL-10; and tumor necrosis factor-alpha - TNF-α). All biomarkers were evaluated via linear regression with adjustments of variables with measures of weight, length, head circumference (HC), chest circumference (CC) and gestational age of newborns at birth, considering p < 0.05 as significant. RESULTS: A total of 100 pregnant women with PE and 50 healthy pregnant women were studied. Higher placental levels of catalase (p = 0.018), SOD (p = 0.031), the GSH/GSSG ratio (p = 0.019) and IL-6 (p = 0.010) and lower GSSG (p = 0.001) were observed in pregnant women with PE than in the control group. Positive associations between placental GSH levels and body weight, HC, CC and gestational age at birth (p < 0.05) were identified. CONCLUSION: PE-derived placentas had high concentrations of some antioxidants (enzymes and thiols), which might be a compensation mechanism against oxidative stress. Placental GSH levels were the only biomarker, among the studied ones, related positively with beneficial perinatal outcomes, suggesting that this endogenous antioxidant plays an important role in maintaining the health of the conceptus and women with PE.