scholarly journals Dysregulated Autophagy Leads to Oxidative Stress and Aberrant Expression of ABC Transporters in Women with Early Miscarriage

Antioxidants ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 1742
Author(s):  
Saira Shahnawaz ◽  
Usman Shah Nawaz ◽  
Jonas Zaugg ◽  
Ghulam Hussain ◽  
Nadia Malik ◽  
...  

Early miscarriage (EMC) is a devastating obstetrical complication. ATP-binding cassette (ABC) transporters mediate cholesterol transfer across the placenta and enhance cell survival by effluxing substrates from target cells in the presence of stressors. Recent evidence reports an intricate interplay between autophagy and ABC transporters. We hypothesized that dysregulated autophagy and oxidative stress (OS) in the placenta leads to abnormal expression of membrane transporters contributing to poor pregnancy survival in EMC. We determined mRNA and protein expression of autophagy genes (Beclin-1/Bcl-2/LC3I/LC3II/p62) and ABC transporters (ABCA1/ABCG1/ABCG2) in placentae from EMC patients (n = 20), term controls (n = 19), first trimester (n = 6), and term controls (n = 5) controls. Oxidative/antioxidant status and biomarkers of oxidative damage were evaluated in maternal serum and placentae from EMC and healthy controls. In EMC, placental expression of LC3II/LC3I as well as of the key autophagy regulatory proteins Beclin-1 and Bcl-2 were reduced, whereas p62 was increased. Both in the serum and placentae of EMC patients, total OS was elevated reflected by increased oxidative damage markers (8-OHdG/malondialdehyde/carbonyl formation) accompanied by diminished levels of total antioxidant status, catalase, and total glutathione. Furthermore, we found reduced ABCG1 and increased ABCG2 expression. These findings suggest that a decreased autophagy status triggers Bcl-2-dependent OS leading to macromolecule damage in EMC placentae. The decreased expression of ABCG1 contributes to reduced cholesterol export to the growing fetus. Increasing ABCG2 expression could represent a protective feedback mechanism under inhibited autophagy conditions. In conclusion, dysregulated autophagy combined with increased oxidative toxicity and aberrant expression of placental ABC transporters affects materno-fetal health in EMC.

Placenta ◽  
2021 ◽  
Vol 112 ◽  
pp. e77
Author(s):  
Saira Shahnawaz ◽  
Muhammad Zahoor Ul Hassan Dogar ◽  
Usman Shah Nawaz ◽  
Nadia Malik ◽  
Jonas Zaugg ◽  
...  

2020 ◽  
Author(s):  
Meihe LI ◽  
Minchao KANG ◽  
Peng AN ◽  
Huimin DANG ◽  
Xin XU

Abstract BackgroundThe normal function of the placenta at each time stage of pregnancy is essential to a successful outcome. Placental dysfunction and increased oxidative stress and autophagy are the cause of a series of severe pregnancy complications. Resveratrol is a potent antioxidant that has shown beneficial effects in many diseases. We aim to investigate whether excessive autophagy is associated with oxidative stress in the trophoblast oxidative stress model. Resveratrol was taken to clarify its role in excessive autophagy of placental trophoblasts. MethodsWe established an in vitro model of oxidative stress by exposing the human first-trimester extravillous trophoblast cell line HTR-8/SVneo to H2O2. Levels of autophagy-related proteins (LC3, Beclin-1, p53 and mTOR) were detected by western blot.ResultsTreatment with resveratrol significantly ameliorated H2O2-induced cytotoxicity, morphological damage, oxidative stress and autophagy. Mechanistically, resveratrol restored the levels of autophagy-related proteins including LC3-II, Beclin-1 and p53, mTOR that were dysregulated by H2O2.ConclusionsResveratrol may protect human trophoblasts against H2O2-induced oxidative stress by reducing excessive autophagy, thus ensuring the normal biological functions of trophoblasts.


Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4573-4573
Author(s):  
Zeynep Karakas ◽  
Yasin Yilmaz ◽  
Dolay Damla Celik ◽  
Agageldi Annayev ◽  
Selcan Demirel ◽  
...  

Abstract Background: The patients with β-thalassemia are usually under oxidative stress due to iron overload as a result of ineffective erythropoiesis and repeated transfusions. The endogen (uric acid, indirect bilirubin) and exogenous (ascorbic acid and vitamin E) antioxidants protect the cells from oxidative damage. The evaluation of antioxidant defense system can be easily done by measuring serum total antioxidant capacity. The aim of this study is to investigate the total oxidant (TOC) and antioxidant capacity (TAC) of patients with transfusion dependent (TDT) and nondependent (NTDT) β -thalassemia. Methods: Fifty eight patients (age range 3-59; median age 24 years) with β-thalassemia (16 nontransfusion dependent, 42 transfusion dependent) who were followed-up by Istanbul Medical Faculty Thalassemia Center were enrolled in this study. The sex and age matched 25 healthy subjects were used as control group. The total oxidant and antioxidant capacity were measured by Rel Assay Diagnostics, Total Oxidant Status (TOS) kit and Total Antioxidant Status (TAS) kit. The statistics of results were done by SPSS version 21. Results: 58 patients were included consisting of β thalassemia intermedia (n=16) and β thalassemia major (n=42). The total oxidant capacity was found higher in patients than control group without significant differences. Beside this, the antioxidant capacity of patients was significantly increased (2.75 mmol/l vs 1.94 mmol/l; p=0.001). Within patients group, there was no significant differences in terms of TAC while the TOC level was high in NTDT (2.99 mmol/l vs 1.88 mmol/l; p=0.08). There was no significant relationship between TOC and sex, age (<18 vs >18 years), ferritin and splenectomy status, as the same for TAC. Conclusions: The oxidative damage in patients with β-thalassemia can trigger the morbidity. The measurement of TOC and TAC status stands a useful, rapid, and simple method to evaluate the complex oxidative mechanism of disease. There are still controversial results about antioxidant status in thalassemia patients. The irregular consume of supportive treatment such as zinc, vitamin C, vitamin E and herbal medicine may affect the TOC and TAC status. The results of this study can guide us to use the antioxidants to decrease the oxidative stress. Figure 1. Figure 1. Disclosures No relevant conflicts of interest to declare.


2015 ◽  
Vol 2015 ◽  
pp. 1-12 ◽  
Author(s):  
Marília Baierle ◽  
Sabrina N. Nascimento ◽  
Angela M. Moro ◽  
Natália Brucker ◽  
Fernando Freitas ◽  
...  

Objective. Cognitive impairment reduces quality of life and is related to vascular and neurodegenerative disorders. However, there is also a close relationship between these diseases and oxidative stress. Thus, the purpose of this study was to assess whether inflammation and oxidative damage are associated with low cognitive performance in the elderly with different housing conditions.Methods. The study groups consisted of 32 institutionalized and 25 noninstitutionalized Brazilian elderly subjects. Oxidative damage, inflammation markers, and cognitive function were evaluated.Results. The results demonstrated pronounced oxidative stress in the institutionalized elderly group, which also had a lower antioxidant status compared to noninstitutionalized subjects. High levels of proinflammatory cytokines were also observed in the institutionalized elderly. Furthermore, the raised levels of inflammatory markers were correlated with increased oxidative stress, and both were associated with low cognitive performance. However, based on multiple linear regression analysis, oxidative stress appears to be the main factor responsible for the cognitive decline.Conclusions. The findings suggest that individuals with lower antioxidant status are more vulnerable to oxidative stress, which is associated with cognitive function, leading to reduced life quality and expectancy.


2010 ◽  
Vol 3 (4) ◽  
pp. 275-282 ◽  
Author(s):  
Nandeslu Gautam ◽  
Subhasis Das ◽  
Santanu Kar Mahapatra ◽  
Subhankari Prasad Chakraborty ◽  
Pratip Kumar Kundu ◽  
...  

Lymphocytes are an important immunological cell and have been played a significant role in acquired immune system; hence, may play in pivotal role in immunosenescence. Oxidative stress has been reported to increase in elderly subjects, possibly arising from an uncontrolled production of free radicals with aging and decreased antioxidant defenses. This study was aimed to evaluate the level of lipid-protein damage and antioxidant status in lymphocytes of healthy individuals to correlate between oxidative damage with the aging process. Twenty healthy individuals of each age group (11–20; 21–30; 31–40; 41–50; and 51–60 years) were selected randomly. Blood samples were drawn by medical practitioner and lymphocytes were isolated from blood samples. Malondialdehyde (MDA), protein carbonyls (PC) level were evaluated to determine the lipid and protein damage in lymphocytes. Superoxide dismutase (SOD), catalase (CAT), glutathione and glutathione dependent enzymes were estimated to evaluate the antioxidant status in the lymphocytes. Increased MDA and PC levels strongly support the increased oxidative damage in elderly subject than young subjects. The results indicated that, balance of oxidant and antioxidant systems in lymphocytes shifts in favor of accelerated oxidative damage during aging. Thus oxidative stress in lymphocytes may particular interest in aging and may play important role in immunosenescence.


2011 ◽  
Vol 2011 ◽  
pp. 1-7 ◽  
Author(s):  
Nedyalka V. Georgieva ◽  
Margarita Gabrashanska ◽  
Ventsislav Koinarski ◽  
Zvezdelina Yaneva

This study was undertaken to determine the dietary supplements of Zn containing diet on the antioxidant status in chickens experimentally infected withEimeria acervulina. The antioxidant status was monitored via determination of MDA concentrations and erythrocyte SOD and CAT activities, as well as vitamin E, vitamin C, Cu, and Zn in liver, muscle, and serum. The results showed increased MDA (), CAT (), and decreased SOD () in the infected birds. Significant changes in Cu and Zn concentrations and dramatically reduction of vitamin C and E concentrations in the infected chickens were found. The observed deviations in the studied enzymes and nonenzymatic parameters evidence the occurrence of oxidative stress following the infection and impaired antioxidant status of chickens, infected withEimeria acervulina. Our results proved the ameliorating role of CuZn(OH)3Cl (0.170 g per kg food) againstEimeria acervulina-induced oxidative damage in infected chickens.


Author(s):  
Hasan Haci Yeter ◽  
Berfu Korucu ◽  
Elif Burcu Bali ◽  
Ulver Derici

Abstract. Background: The pathophysiological basis of chronic kidney disease and its complications, including cardiovascular disease, are associated with chronic inflammation and oxidative stress. We investigated the effects of active vitamin D (calcitriol) and synthetic vitamin D analog (paricalcitol) on oxidative stress in hemodialysis patients. Methods: This cross-sectional study was composed of 83 patients with a minimum hemodialysis vintage of one year. Patients with a history of any infection, malignancy, and chronic inflammatory disease were excluded. Oxidative markers (total oxidant and antioxidant status) and inflammation markers (C-reactive protein and interleukin-6) were analyzed. Results: A total of 47% (39/83) patients were using active or analog vitamin D. Total antioxidant status was significantly higher in patients with using active or analog vitamin D than those who did not use (p = 0.006). Whereas, total oxidant status and oxidative stress index were significantly higher in patients with not using vitamin D when compared with the patients who were using vitamin D preparation (p = 0.005 and p = 0.004, respectively). On the other hand, total antioxidant status, total oxidant status, and oxidative stress index were similar between patients who used active vitamin D or vitamin D analog (p = 0.6; p = 0.4 and p = 0.7, respectively). Conclusion: The use of active or selective vitamin D analog in these patients decreases total oxidant status and increases total antioxidant status. Also, paricalcitol is as effective as calcitriol in decreasing total oxidant status and increasing total antioxidant status in patients with chronic kidney disease.


VASA ◽  
2017 ◽  
Vol 46 (4) ◽  
pp. 268-274
Author(s):  
Erhan Saraçoğlu ◽  
Ertan Vuruşkan ◽  
Yusuf Çekici ◽  
Salih Kiliç ◽  
Halil Ay ◽  
...  

Abstract. Background: After carotid artery stenting (CAS), neurological complications that cannot be explained with imaging methods may develop. In our study we aimed to show, using oxidative stress markers, isolated oxidative damage and resulting neurological findings following CAS in patients with asymptomatic carotid artery stenosis. Patients and methods: We included 131 neurologically asymptomatic patients requiring CAS. The neurological findings were evaluated using the modified Rankin Scale (mRS) prior to the procedure, one hour post-procedure, and two days after. Patients with elevated mRS scores but with or without typical hyperintense lesions observed on an MRI and with changes of oxidative stress marker levels at the time (Δtotal-thiol, Δtotal antioxidative status [TAS], and Δtotal oxidant status [TOS]) were evaluated. Results: In the neurological examination carried out one hour prior to the procedure, there were 92 patients with mRS = 0, 20 with mRS = 1, and 12 with mRS = 2. When Δtotal-thiol, ΔTAS, and ΔTOS values and the mRS were compared, it was observed that as the difference in oxidative parameters increased, clinical deterioration also increased proportionally (p = 0.001). Conclusions: We demonstrate a possible correlation between oxidative damage and neurological findings after CAS which could not be explained by routine imaging methods.


Reproduction ◽  
2000 ◽  
pp. 143-149 ◽  
Author(s):  
RM Sainz ◽  
RJ Reiter ◽  
JC Mayo ◽  
J Cabrera ◽  
DX Tan ◽  
...  

Pregnancy is a physiological state accompanied by a high energy demand of many bodily functions and an increased oxygen requirement. Because of the increased intake and utilization of oxygen, increased levels of oxidative stress would be expected. In the present study, the degree of lipid peroxidation was examined in different tissues from non-pregnant and pregnant rats after the delivery of their young. Melatonin and other indole metabolites are known to be direct free radical scavengers and indirect antioxidants. Thus the effect of pinealectomy at 1 month before pregnancy on the accumulation of lipid damage was investigated in non-pregnant and pregnant rats after the delivery of their young. Malonaldehyde and 4-hydroxyalkenal concentrations were measured in the lung, uterus, liver, brain, kidney, thymus and spleen from intact and pinealectomized pregnant rats soon after birth of their young and at 14 and 21 days after delivery. The same parameters were also evaluated in intact and pinealectomized non-pregnant rats. Shortly after delivery, lipid oxidative damage was increased in lung, uterus, brain, kidney and thymus of the mothers. No differences were detected in liver and spleen. Pinealectomy enhanced this effect in the uterus and lung. It is concluded that during pregnancy high levels of oxidative stress induce an increase in oxidative damage to lipids, which in some cases is inhibited by the antioxidative actions of pineal indoles.


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