scholarly journals Kidney dysfunction in the low-birth weight murine adult: implications of oxidative stress

2018 ◽  
Vol 315 (3) ◽  
pp. F583-F594 ◽  
Author(s):  
Wasan Abdulmahdi ◽  
May M. Rabadi ◽  
Edson Jules ◽  
Yara Marghani ◽  
Noor Marji ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Birth Weight ◽  
Endothelial Dysfunction ◽  
Low Birth Weight ◽  
Vascular Dysfunction ◽  
Vascular Density ◽  
Immunofluorescence Analysis ◽  
Doppler Flowmetry ◽  
Maternal Undernutrition ◽  
Nephron Endowment

Maternal undernutrition (MUN) during pregnancy leads to low-birth weight (LBW) neonates that have a reduced kidney nephron endowment and higher morbidity as adults. Using a severe combined caloric and protein-restricted mouse model of MUN to generate LBW mice, we examined the progression of renal insufficiency in LBW adults. Through 6 mo of age, LBW males experienced greater albuminuria (ELISA analysis), a more rapid onset of glomerular hypertrophy, and a worse survival rate than LBW females. In contrast, both sexes experienced a comparable progressive decline in renal vascular density (immunofluorescence analysis), renal blood flow (Laser-Doppler flowmetry analysis), glomerular filtration rate (FITC-sinistrin clearance analysis), and a progressive increase in systemic blood pressure (measured via tail-cuff method). Isolated aortas from both LBW sexes demonstrated reduced vasodilation in response to ACh, indicative of reduced nitric oxide bioavailability and endothelial dysfunction. ELISA and immunofluorescence analysis revealed a significant increase of circulating reactive oxygen species and NADPH oxidase type 4 (NOX4) expression in both LBW sexes, although these increases were more pronounced in males. Although more effective in males, chronic tempol treatment did improve all observed pathologies in both sexes of LBW mice. Chronic NOX4 inhibition with GKT137831 was more effective than tempol in preventing pathologies in LBW males. In conclusion, despite some minor differences, LBW female and male adults have a reduced nephron endowment comparable with progressive renal and vascular dysfunction, which is associated with increased oxidative stress and subsequent endothelial dysfunction. Tempol treatment and/or NOX4 inhibition attenuates renal and vascular dysfunction in LBW adults.

scholarly journals Maternal Supply of Cysteamine during Late Gestation Alleviates Oxidative Stress and Enhances Angiogenesis in Porcine Placenta

2021 ◽  
Author(s):  
Shuangbo Huang ◽  
Zifang Wu ◽  
Xiangyu Hao ◽  
Zihao Huang ◽  
Longmiao Zhang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Birth Weight ◽  
Low Birth Weight ◽  
Oxidative Damage ◽  
Mrna Level ◽  
Late Gestation ◽  
Vascular Density ◽  
Vascular Endothelial ◽  
Positive Effects

Abstract Background: Oxidative stress in placenta is associated with the occurrence of adverse pregnancy outcomes in sow, but there are few satisfactory treatment strategies for these conditions. This study investigated the potential of cysteamine (CS) as an antioxidant protectant for regulating the reproductive performance, redox status, and placental angiogenesis of sows.Methods: The placental oxidative stress status and vascular density of piglets with different birth weights: <1.0 kg (low birth weight, LBW) and 1.4-1.6 kg (normal birth weight, NBW) were evaluated, followed by allotting 84 sows to four treatments (n=21) and feeding them with a basal diet supplemented with 0, 100, 300, or 500 mg/kg of CS (CON, CS100, CS300, and CS500 diet) from day 85 of gestation to day 21 of lactation, respectively. Placentae, serum and colostrum, and blood samples of sows or piglets were collected, and the characteristics of sows and piglets were recorded. Furthermore, the in vivo results were validated using porcine vascular endothelial cells (PVECs).Results: The placentae for the LBW piglets had higher oxidative damage and lower vascular density than those for the NBW piglets (P < 0.05). Further experiments with sows showed that compared with the CON group, the CS100 group was lower in the stillbirth and invalid rates, and higher in the piglet birth weight and placental efficiency (P < 0.05). Meanwhile, the CS100 group also displayed higher glutathione and lower malondialdehyde in both the serum and colostrum of sows (P < 0.05). Interestingly, compared to the CON group, the LBW placentae of the CS100 group showed a decrease in oxidative damage, while an increase in vascular density (P < 0.05), as well as the mRNA level of vascular endothelial growth factor A and the immunostaining intensity of platelet endothelial cell adhesion molecule-1 (P < 0.05). Furthermore, the in vitro experiment indicated that CS pre-treatment could significantly reverse the NADPH oxidase 2-ROS-mediated inactivation of signal transducer and activator of transcription-3 (Stat3) signaling pathway induced by H2O2 inhibition of the proliferation, tube formation, and migration of PVECs (P < 0.05).Conclusions: The results indicated that oxidative stress and impaired angiogenesis might contribute to the occurrence of low-birth-weight piglets during pregnancy, but CS supplementation at 100 mg/kg during late gestation and lactation of sows could alleviate oxidative stress and enhance angiogenesis in placenta, thereby improving pregnancy outcome. The in vitro data showed that the underlying mechanism for the positive effects of CS may be related to the activation of Stat3.

scholarly journals Hypoxia and Oxidative Stress Are Associated with Reduced Fetal Growth in Twin and Undernourished Sheep Pregnancies

Animals ◽  
2018 ◽  
Vol 8 (11) ◽  
pp. 217 ◽  
Author(s):  
Francisco Sales ◽  
Oscar Peralta ◽  
Eileen Narbona ◽  
Sue McCoard ◽  
Mónica De los Reyes ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Birth Weight ◽  
Low Birth Weight ◽  
Cord Blood ◽  
Fetal Growth ◽  
Fetal Growth Restriction ◽  
Growth Restriction ◽  
Maternal Undernutrition ◽  
Natural Pasture ◽  
And Oxidative Stress

Low birth weight has profound implications for perinatal mortality and morbidity in lambs, causing higher mortality and lower growth potential. Low birth weight, as a consequence of fetal growth restriction, occurs in undernourished and multiple pregnancies, where hypoxia and oxidative stress could play a critical role. Our aim was to establish the effects of nutritional deprivation and pregnancy rank on fetal growth, oxygenation, and oxidative status in sheep pregnancies under extensive Patagonian conditions. At 30 days after mating, single- and twin-bearing ewes were offered only natural pasture (undernutrition group) or natural pasture plus concentrate supplementation (well-nourished group). At day 140 of gestation, blood gases and redox status were evaluated in venous cord blood, and fetal biometric characteristics were obtained after cesarean section. Both maternal undernutrition and twinning led to decreased oxygen supply to the fetuses (p = 0.016 and p = 0.050, respectively), which was associated with decreased intrauterine growth (r = 0.446, p < 0.01). Moreover, twinning increased oxidative stress in cord blood (p < 0.05), which might also contribute to fetal growth restriction. These results reinforce the importance of maternal nutrition, especially for those ewes bearing multiples, and opens new possibilities for nutritional or antioxidant interventions for preventing fetal hypoxia and oxidative stress.

Abstract MP30: Circulating Sars-cov-2 Spike Protein 1 Causes Microarteriolar Oxidative Stress, Endothelial Dysfunction And Enhanced Thromboxane And Endothelin Contractility That Are Prevented By Spironolactone.

Hypertension ◽  
2021 ◽  
Vol 78 (Suppl_1) ◽  
Author(s):  
Dan Wang ◽  
Christopher S Wilcox
Keyword(s):  
Oxidative Stress ◽  
Endothelial Cells ◽  
Endothelial Dysfunction ◽  
Fluorescence Microscopy ◽  
Vascular Dysfunction ◽  
Microvascular Complications ◽  
Spike Protein ◽  
Ros Generation ◽  
Intravenous Injections ◽  
Novel Model

Introduction and hypothesis: Following bodily entry, the SARS-CoV-2 virus undergoes pulmonary replication with release of circulating viral spike protein 1 (SP1) into the bloodstream. Uptake of SP1 by endothelial cells might provoke vascular dysfunction and thrombosis. We hypothesized that spironolactone could prevent microvascular complications from circulating SP1 in COVID-19. Methods: male C57Bl/6 mice received spironolactone (100 mg · kg -1 · d -1 PO x 3d) or vehicle and intravenous injections of recombinant full-length human SP1 (10 μg per mouse) or vehicle. They were euthanized after 3 days. Mesenteric resistant arterioles (n=4 per group) were dissected and mounted on isometric myographs. Acetylcholine-induced EDRF responses and L-NAME-inhibitable NO generation (DAF-FM fluorescence) were studied in pre-constricted vessels and contraction to endothelin 1 (ET1) or thromboxane (U-46, 619) and ET1-induced ROS (PEG-SOD inhibitable ethidium: dihydroethidium fluorescence) were studied by fluorescence microscopy in other vessels. Results: SP1 reduced acetylcholine-induced EDRF (17 ± 3 vs 27 ± 5 % mean ± sem; P < 0.05) and NO generation (0.21 ± 0.03 vs 0.36 ± 0.04, F 1 /F 0 ; P < 0.05) while increasing contraction to ET1 (10 -7 mol·l -1 : 124 ± 13 vs 89 ± 4 %; P < 0.05) and U-46, 619 (10 -6 mol·l -1 :114± 5 vs 87± 6 %; P < 0.05) and ET1-induced ROS generation(0.30± 0.08 vs 0.09± 0.03; P < 0.05). Spironolactone did not modify any of these responses in vessels from normal mice but prevented all the effects of SP1. Conclusion: these preliminary studies provide a novel model to study COVID-19 vasculopathy. They indicate that spironolactone can provide protection from microvascular oxidative stress, endothelial dysfunction and enhanced contractility and might thereby moderate COVID-19 complications.

scholarly journals Association between Maternal Dietary Diversity and Low Birth Weight in Central India: A Case-Control Study

2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Shantanu Sharma ◽  
Sonali Maheshwari ◽  
Sunil Mehra
Keyword(s):  
Birth Weight ◽  
Low Birth Weight ◽  
Case Control Study ◽  
Dietary Diversity ◽  
Central India ◽  
Case Control ◽  
Reproductive Age ◽  
Stepwise Logistic Regression ◽  
Maternal Undernutrition ◽  
Control Study

Low birth weight (LBW) is one of the major public health challenges in India. LBW etiology is multifactorial and linked to multiple determinants, including maternal undernutrition and sociodemographic characteristics. The objective of the present endeavor was to assess how maternal dietary diversity and other sociodemographic factors among marginalized populations are associated with the incidence of LBW. The study was a part of the community-based intervention that aimed to improve maternal and child health in the Morena district of Madhya Pradesh, a state in central India. In this case-control study, cases were defined as mothers with an LBW child (<2500 grams) and controls as mothers without an LBW child. A quantitative survey was done with women of reproductive age, having at least one child aged 0–24 months. We calculated the dietary diversity based on the number of food groups consumed during pregnancy by women on a daily basis. Stepwise logistic regression models were built to test for associations between sociodemographic and dietary diversity variables and LBW incidence. There were 157 mothers with and 214 without an LBW child. Women’s diets mainly consisted of grains, such as wheat, rice, maize, and roots and tubers. Eggs and meat were consumed by less than 1% of the women. There were 20% lesser chances of an LBW child with increasing maternal dietary diversity scores (odds ratio: 0.79; 95% CI: 0.65, 0.96). The poor maternal diet quality during pregnancy may result in adverse birth outcomes with long-term consequences in a child.

scholarly journals A comparative analysis of determinants of low birth weight and stunting among under five children of adolescent and non-adolescent mothers using 2015/16 Tanzania Demographic and Health Survey (TDHS)

BMC Nutrition ◽  
2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Ramadhani H. Mtongwa ◽  
Charles Festo ◽  
Ester Elisaria
Keyword(s):  
Socioeconomic Status ◽  
Birth Weight ◽  
Low Birth Weight ◽  
Adolescent Mothers ◽  
Maternal Age ◽  
Maternal Obesity ◽  
Maternal Body Mass Index ◽  
Child Birth ◽  
Maternal Undernutrition ◽  
Children Under 5

Abstract Background Tanzania is one of the Sub-Saharan African country with nearly 12 out of 60 million people being adolescent. The prevalence of child marriage is higher with one out of every three girls being married before reaching their 18th birthday, 5 % being married by the age of 15, and 31% by the age of 18 years. Literature shows early pregnancy is associated with Low Birth Weight (LBW) and stunting among children under 5 years. This paper explores variation and factors associated with low birth weight and stunting among children born by adolescent and non-adolescent mothers. Methods Data from 13,266 women with children under 5 years collected as part of the 2015/2016 TDHS was re-analyzed using STATA version 14 software while accounting for survey design. A total of 6385 women (of which 7.2% were adolescent) and 8852 women (of which 6.7% were adolescent) were involved in the analysis of child birth weight and stunting respectively. Descriptive statistics stratified by maternal age was conducted with LBW and stunting as outcome variables followed by logistic regressions models controlling for confounding variables. Results The proportion of obese or overweight adolescent and non-adolescent mothers was 11.8 and 36.5% respectively. Antenatal care (ANC) attendance, areas of residence and social economic status were very similar in the two maternal age groups. Non- adolescent mothers had reduced odds of giving birth to LBW babies compared to adolescent mothers (Adjusted Odds Ratio (AOR) = 0.34; 95% CI: 0.22–0.50). Maternal undernutrition (AOR = 2.29; 95% CI: 1.43–3.67), being divorced, separated or widowed (AOR = 1.76; 95% CI: 1.24–2.50) and having at least four ANC visits (AOR = 0.64; 95% CI: 0.49–0.83) were significantly associated with reduced odds of having a LBW. Child stunting was not associated with maternal age. Maternal high socioeconomic status (AOR = 0.69; 95% CI: 0.57–0.84) and maternal obesity or overweight (AOR = 0.77; 95% CI: 0.64–0.92) were negatively associated with stunting. Child birth weight, sex, and age were significantly associated with stunting. Conclusion Maternal age was a predictor of LBW but not stunting. ANC attendance and not living with a spouse increase the risk of LBW babies. Stunting was associated with low maternal body mass index (BMI), low socioeconomic status, child birth weight, gender, and age. A multi-sectoral approach is needed to address child nutrition problems with teenagers ‘specific intervention that offer emotional support, and health education during pregnancies for improving immediate and later life child birth outcomes.

scholarly journals Women’s empowerment is associated with maternal nutrition and low birth weight: Evidence from Bangladesh Demographic Health Survey

2020 ◽  
Author(s):  
Alamgir Kabir ◽  
Md Mahbubur Rashid ◽  
Kamal Hossain ◽  
Md Arifuzzaman Khan ◽  
Shegufta Shefa Sikder ◽  
...  
Keyword(s):  
Decision Making ◽  
Birth Weight ◽  
Low Birth Weight ◽  
Health Survey ◽  
Maternal Nutrition ◽  
Women's Empowerment ◽  
Wealth Quintile ◽  
Women’S Empowerment ◽  
Demographic Health Survey ◽  
Maternal Undernutrition

Abstract Background The burden of maternal undernutrition and low birth weight (LBW) incurs enormous economic costs due to their adverse consequences. Women’s empowerment is believed to be one of the key factors for attaining maternal and child health and nutritional goals. Our objective was to investigate the association of women’s empowerment with maternal undernutrition and LBW. Methods We used nationally representative data from the Bangladesh Demographic Health Survey for 2011 and 2014. We analysed 27,357 women and 9,234 mother-child pairs. A women’s empowerment index (WEI) was constructed using principal component analysis with five groups of indicators: a) education, b) access to socio-familial decision making, c) economic contribution and access to economic decision making, d) attitudes towards domestic violence and e) mobility. We estimated odds ratios as the measure of association between the WEI and the outcome measures using generalized estimating equations to account for the cluster level correlation. Results The overall prevalence of maternal undernutrition was 20% and LBW was 18%. The WEI was significantly associated with both maternal undernutrition and LBW with a dose-response relationship. The adjusted odds of having a LBW baby was 32% [AOR (95% CI):0.68 (0.57, 0.82)] lower in the highest quartile of the WEI relative to the lowest quartile. Household wealth significantly modified the effect of the WEI on maternal nutrition.; in the highest wealth quintile, the odds of maternal undernutrition was 54% [AOR (95% CI): 0.46 (0.33, 0.64)] lower while in the lowest wealth quintile the odds of undernutrition was only 18% [AOR (95% CI): 0.82 (0.67, 1.00)] lower comparing the highest WEI quartile with the lowest WEI quartile. However, the absolute differences in prevalence of undernutrition between the highest and lowest WEI quartiles were similar across wealth quintiles (6-8%). Conclusions This study used a comprehensive measure of women’s empowerment and provides strong evidence that low levels of women’s empowerment is associated with maternal undernutrition as well as with delivering LBW babies in Bangladesh. Therefore, policies to increase empowerment of women would contribute to improved public health.

scholarly journals APOE4 genotype increases neuronal calcium signals and decreases pial arteriole responsivity and vasomotion in visual cortex of awake mice

2021 ◽  
Author(s):  
Orla Bonnar ◽  
Kira Shaw ◽  
Dori M Grijseels ◽  
Devin Clarke ◽  
Laura Bell ◽  
...  
Keyword(s):  
Blood Flow ◽  
Visual Stimulation ◽  
Late Onset ◽  
Vascular Dysfunction ◽  
Beta Amyloid ◽  
Blood Oxygenation ◽  
Vascular Density ◽  
Calcium Signals ◽  
Doppler Flowmetry ◽  
Acute Surgery

Vascular dysfunction is an early feature of late onset Alzheimer's disease (AD), preceding classic AD pathology such as beta amyloid accumulation and formation of hyperphosphorylated tau. Such vascular dysfunction may promote classic AD pathology by decreasing blood flow, impairing brain oxygenation and clearance of molecules such as beta amyloid. The main genetic risk factor for AD is the ϵ4 allele of APOE, which has been found to increase blood brain barrier permeability and decrease vascular density, as well as decrease blood flow and functional hyperaemia in anaesthetised mice undergoing acute surgery. These results suggest that APOE4 may confer AD risk via its effects on the vasculature. However, the responses of neurons and individual vessels have not been studied, so neurovascular relationships are unknown, and no previous studies have looked at awake mice. We therefore measured neurovascular responses at rest and in response to visual stimulation using 2 photon imaging of awake APOE3 and APOE4 targeted-replacement (APOE TR) mice that expressed the calcium indicator GCaMP6f in excitatory neurons, while labelling the vascular lumen with Texas Red dextran. In parallel, we measured cerebral blood flow, blood oxygenation and cerebral blood volume using combined laser Doppler flowmetry and haemoglobin spectrometry. Measurements were performed in mice aged between 3-4 months to 12-13 months. We found a milder vascular deficit in awake mice than previous studies that used an acute surgical preparation: capillary responses to visual stimulation were the same in APOE3 and APOE4 TR mice, leading to unimpaired functional hyperaemia. However, neuronal calcium signals during visual stimulation were significantly enhanced in APOE4 mice, while there was a marked decrease in pial arteriole responsiveness and vasomotion. This pattern of results was unaffected by age, suggesting that APOE4 expression creates a stable, but mildly altered neurovascular state that does not itself cause degeneration. However, these changes likely make the system more sensitive to subsequent insults; for example, weaker vasomotion could impair clearance of beta amyloid as it starts to accumulate, and therefore may help explain how APOE4 expression increases risk of developing AD.

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