Increase In Oxidative Stress Markers Research Articles

Oxidative stress in breast cancer after chemotherapy.

It is of interest to evaluate the influence of breast cancer on oxidative stress, liver function tests, renal biomarkers, action of doxorubicin, cyclophosphamide and paclitaxel (AC-T) in the treatment and mechanism over altering the measured markers in breast cancer. Sixty histopathological confirmed cases of female patients suffering with breast carcinoma from the Department of Oncology at Omega Cancer Hospital, Visakhapatnam were included in the study. The investigation was performed in 3 groups: a control group containing 30 healthy females of similar age, 30 breast cancer patients without treatment and 30 patients receiving treatment with anticancer combination drugs AC-T. The venous blood samples from both controls and patients were measured for total antioxidant status (TAS), nitric oxide (NO), malondialdehyde, alanine aminotransferase, aspartate aminotransferase, and blood urea, serum creatinine. One-way ANOVA and Tukey-Kramer multiple comparisons post-test were applied as statistical analysis tools through SPPS software version 20.0. P<0.05 was regarded as significant. According to the findings, higher stages of breast cancer were linked to considerable increase in oxidative stress markers during AC-T treatment. The findings of the study revealed that oxidative stress is linked to breast cancer, and that chemotherapy exacerbates this oxidative stress, causing damage to a variety of cellular targets. Monitoring serum oxidative stress markers may aid in the evaluation of chemotherapy effects in breast cancer patients. According to our findings, AC-T chemotherapy will elevate malondialdehyde, a lipid peroxidation marker, and lowers the total antioxidant status.

Effect of Bisphenol S on testicular tissue after low-dose lactation exposure

Exposure to endocrine disruptors such as bisphenols, can lead to and be the explanation for idiopathic infertility. In our study, we assessed the effect of exposure to bisphenol S (BPS) via breast milk on the testicular tissue health of adult male mice. Lactating dams were exposed to BPS through drinking water (0.216 ng g bw/day and 21.6 ng g bw/day) from post-natal day 0–15. Although there was no significant difference in testicular histopathology between the control and experimental groups, we observed an increase in the number of tight and gap junctions in the blood-testis barrier (BTB) of adult mice after lactation BPS exposure. Moreover, there was an increase in oxidative stress markers in adult testicular tissue of mice exposed via breast milk. Our lactation model indicates that breast milk is a route of exposure to an endocrine disruptor that can be responsible for idiopathic male infertility through the damage of the BTB and weakening of oxidative stress resistance in adulthood.

Cerrahi Menopoz ve Kronik Serebral Hipoperfüzyon Oluşturulmuş Sıçanlarda Spironolaktonun Prefrontal Korteks ve Göz Dokularında Glikojen ve Oksidatif Stres Parametreleri Üzerine Etkisi

Amaç: Kronik serebral hipoperfüzyon (KSH), ilerleyici hipokampal hasar ve bilişsel bozukluklarla&#x0D; birlikte vasküler demansa yol açar. KSH retinadaki kan akımında da azalmaya neden olmaktadır. Bu&#x0D; çalışmanın amacı KSH oluşturulmuş overektomize sıçanlarda spironolaktonun göz ve prefrontal korteks&#x0D; (PFC) dokularındaki oksidatif stres ve glikojen seviyelerine etkilerini araştırmaktır.&#x0D; Gereç ve Yöntemler: Wistar Albino cinsi 32 adet dişi sıçan, her grupta 8 adet olacak şekilde rastgele&#x0D; 4 gruba ayrıldı: 1)Kontrol, 2)KSH, 3)KSH+Spironolakton 25mg/kg 4)KSH+Spironolakton 50mg/kg.&#x0D; Sıçanlara deneyin başlangıcında bilateral ovariektomi (OVX) uygulandı, OVX’ten 5 hafta sonra ortak&#x0D; bilateral ortak karotid arter oklüzyonu (2VO) ile KSH modeli oluşturuldu. Spironolakton 2VO’dan üç gün&#x0D; önce ve 2VO’dan sonra 3 hafta boyunca günde 1 kez oral gavaj yoluyla uygulandı. Deney sonunda&#x0D; doku glikojen, indirgenmiş glutatyon (GSH), malondialdehid (MDA) ve AA düzeyleri ölçüldü. İstatistiksel&#x0D; analiz ANOVA ve Bonferroni testleri kullanılarak yapıldı.&#x0D; Bulgular: KSH, PFC’de oksidatif stres belirteçlerinde artışa ve glikojen düzeyinde bir azalmaya neden&#x0D; oldu. Benzer şekilde KSH göz dokusunda hem glikojen hem de AA düzeyinde azalmaya neden oldu.&#x0D; Spironolaktonun 25 mg/kg dozu ile tedavi edilen grupta KSH grubuna kıyasla göz AA ve PFC glikojen&#x0D; düzeyleri azalırken PFC’deki MDA düzeyi artmış olarak bulundu (p

MeHg exposure impairs both the catecholaminergic and cholinergic systems resulting in motor and non-motor behavioral changes in Drosophila melanogaster

Human exposure to the natural environmental contaminant methylmercury (MeHg) has been associated to adverse health effects. Importantly, the mechanisms by which this organomercurial exerts its neurotoxicity have yet to be fully clarified. Therefore, the aim of this study was to evaluate whether exposure to MeHg alters dopamine (DA) and octopamine (OA) levels, acetylcholinesterase (AChE) activity and impacts both motor and non-motor behaviours. We studied the effect of MeHg by feeding 1–2 d old flies (male and females) with 25 and 50 μM MeHg for 4 d and determined effects on survival, motor and non-motor behaviours, oxidative stress, AChE and tyrosine hydroxylase (TH) activities, as well as DA and OA levels. We found that Drosophila melanogaster (D. melanogaster) exposed to MeHg showed a reduction in survival rate, associated with the inhibition of AChE and TH activities in head of flies and decreased DA and OA levels. These changes were accompanied by behavioural alterations, such as locomotor deficit and increased grooming behaviour, in addition to an increase in oxidative stress markers both in head and in body of flies, and an increase in glutathione-S-transferase (GST) activity in head of flies. Collectively, our data support the hypothesis that MeHg neurotoxicity is associated with altered OA and DA levels, AChE inhibition, which may serve, at least in part, as the underpinnings of both motor and non-motor behavioural changes.

Non-steroidal anti-inflammatory drugs caused an outbreak of inflammation and oxidative stress with changes in the gut microbiota in rainbow trout (Oncorhynchus mykiss)

One of the main contributors to pharmaceutical pollution of surface waters are non-steroidal anti-inflammatory drugs (NSAIDs) that contaminate the food chain and affect non-target water species. As there are not many studies focusing on toxic effects of NSAIDs on freshwater fish species and specially effects after dietary exposure, we selected rainbow trout (Oncorhynchus mykiss) as the ideal model to examine the impact of two NSAIDs – diclofenac (DCF) and ibuprofen (IBP). The aim of our study was to test toxicity of environmentally relevant concentrations of these drugs together with exposure doses of 100× higher, including their mixture; and to deepen knowledge about the mechanism of toxicity of these drugs. This study revealed kidneys as the most affected organ with hyalinosis, an increase in oxidative stress markers, and changes in gene expression of heat shock protein 70 to be signs of renal toxicity. Furthermore, hepatotoxicity was confirmed by histopathological analysis (i.e. dystrophy, congestion, and inflammatory cell increase), change in biochemical markers, increase in heat shock protein 70 mRNA, and by oxidative stress analysis. The gills were locally deformed and showed signs of inflammatory processes and necrotic areas. Given the increase in oxidative stress markers and heat shock protein 70 mRNA, severe impairment of oxygen transport may be one of the toxic pathways of NSAIDs. Regarding the microbiota, an overgrowth of Gram-positive species was detected; in particular, significant dysbiosis in the Fusobacteria/Firmicutes ratio was observed. In conclusion, the changes observed after dietary exposure to NSAIDs can influence the organism homeostasis, induce ROS production, potentiate inflammations, and cause gut dysbiosis. Even the environmentally relevant concentration of NSAIDs pose a risk to the aquatic ecosystem as it changed O. mykiss health parameters and we assume that the toxicity of NSAIDs manifests itself at the level of mitochondria and proteins.

Zinc-loaded whey protein nanoparticles alleviate the oxidative damage and enhance the gene expression of inflammatory mediators in rats

BackgroundZinc (Zn) is an essential trace element required for the function of the immune system. However, Zn fortification of food has faced some challenges, although excess Zn may be induced obesity and other related. This study aimed to use Zn-loaded whey protein nanoparticles (Zn-WPNPs) to enhance the immunomodulatory activity of Zn in rats treated with CCl4. MethodsZn was loaded to WPNPs at a level of 14 mg/g. Four experimental groups of male albino Wistar rats were treated for 30 days including the control group, CCl4-treated group (0.5 ml/100 g b.w), Zn plus CCl4-treated group (50 mg/kg b.w), and CCl4 plus Zn-WPNPs-treated group (50 mg/kg b.w). Blood and tissue samples were collected for different assays and histological examinations. ResultsThe results revealed that CCl4 disturbs the serum biochemical, hematological, and immune indicators in different organs besides the liver as a target organ. Animals that received CCl4 showed a significant increase in oxidative stress markers, cytokines, and the mRNA expression of inflammatory mediators in the lung and spleen accompanied by a significant decrease in the hepatic and renal antioxidant enzymes along with histological changes in the liver, kidney, spleen, and lung. Zn or Zn-WPNPs could improve these parameters and the histological picture of the tested organs and Zn-WPNPs were more effective than Zn alone. ConclusionWPNPs induced synergistic immune-modulating effects which may control Zn release and may be a suitable candidate to enhance the immune system during any pandemic or the exposure to any chemicals that affect the immune system.

Regulation of PTU-induced hypothyroidism in rats by caffeic acid primarily by activating thyrotropin receptors and by inhibiting oxidative stress

BackgroundEarlier, nothing was known on the thyroid-regulatory potential of caffeic acid (CA). We investigated its role in 6-propyl-thiouracil (PTU)-induced hypothyroid rats and also worked out the possible involvement of 5’-deiodinase I (5’-DI) and thyrotropin receptor (TSHR) in its mode of action. MethodsA pre-standardized dose (100 mg/kg) of CA was orally administered to PTU-induced rats for 30 days and its effects were evaluated on the alterations in the levels of serum triiodothyronine (T3), thyroxine (T4), thyrotropin (TSH) and hepatic 5’-D1activity; expression of thyroid TSHR, aspartate transaminase (AST), alanine transaminase (ALT), tumour necrosis factor-α (TNF-α), interleukin-6 (IL-6), total cholesterol (CHOL), triglycerides (TG) and hepatic lipid peroxidation (LPO). For the first time an interaction of CA with TSHR was studied in silico. ResultsPTU significantly reduced serum levels of thyroid hormones (TH), hepatic 5’-D1 and antioxidant activities as well as TSHR expression, but increased the serum TSH, AST, ALT, TNF-α, IL-6, CHOL, TG and hepatic LPO. However, CA treatment ameliorated all these PTU-induced alterations near to normal levels. Further, the distorted histo-architecture of thyroid gland by PTU was corrected by this compound. The molecular docking study indicated that CA possesses a high binding free energy with target TSHR. These results were comparable to that of a standard pro-thyroid drug, thyroxine. ConclusionCA potentially stimulated thyroid function by increasing TH levels, hepatic 5’-D1 activity and upregulation of TSHR protein expression. In addition, it attenuated the increase in oxidative stress markers, liver markers, lipids and improved the thyroid histo-architecture, thus protected from PTU-induced adverse effects. In silico studies suggested the interaction of CA with TSHR that yielded the binding energy (-6.51 kcal/mol) as compared to thyroxine (-6.10 kcal/mol) suggesting it as a highly potent thyro-stimulatory drug.

Memory, neurogenic protein and oxidative deficits of frontal cortex following chlorpyrifos/dichlorvos exposure in rats

Objective: The use of xenobiotics to boost agricultural productivity has led to toxic chemicals exposure including organophosphates, causing adverse health outcomes including behavioral and neuronal impairments. This study aimed to evaluate the memory indices, possible oxidative and cholinesterase outturnson the frontal cortices of rats exposed to organophosphates.Methodology: Thirty-two Wistar rats were grouped into four. They received 1ml/kg of Normal, 8.8 mg/kg dichlorvos, 14.9 mg/kg chlopyrifos, and 8.8 mg/kg dichlorvos plus 14.9mg/kg chlorpyrifos respectively. They had training trials in the Y Maze paradigm then spatial working memory assessment. They were euthanized 24hours following exposure and tissues excised for analysis.Results: A marked reduction in metabolic markers, Acetylcholine Esterase (AChE) activity, spatial memory indices and proliferative neuron marker (Ki67) were observed. Also, increase in oxidative stress markers in the frontal cortices of the organophosphates exposed rats.Conclusion: The findings demonstrated neurotoxic effects of organophosphates in rats.

Oxidative Stress in Chronic Obstructive Pulmonary Disease.

There is a marked increase in oxidative stress in the lungs of patients with COPD, as measured by increased exhaled 8-isoprostane, ethane, and hydrogen peroxide in the breath. The lung may be exposed to exogenous oxidative stress from cigarette smoking and indoor or outdoor air pollution and to endogenous oxidative stress from reactive oxygen species released from activated inflammatory cells, particularly neutrophils and macrophages, in the lungs. Oxidative stress in COPD may be amplified by a reduction in endogenous antioxidants and poor intake of dietary antioxidants. Oxidative stress is a major driving mechanism of COPD through the induction of chronic inflammation, induction of cellular senescence and impaired autophagy, reduced DNA repair, increased autoimmunity, increased mucus secretion, and impaired anti-inflammatory response to corticosteroids. Oxidative stress, therefore, drives the pathology of COPD and may increase disease progression, amplify exacerbations, and increase comorbidities through systemic oxidative stress. This suggests that antioxidants may be effective as disease-modifying treatments. Unfortunately, thiol-based antioxidants, such as N-acetylcysteine, have been poorly effective, as they are inactivated by oxidative stress in the lungs, so there is a search for more effective and safer antioxidants. New antioxidants in development include mitochondria-targeted antioxidants, NOX inhibitors, and activators of the transcription factor Nrf2, which regulates several antioxidant genes.

Naringenin antihypertensive power is mediated via abrogation of mineralocorticoid receptor (MCR)/ angiotensin converting enzyme (ACE)/ kidney injury molecule (Kim‐1) signaling pathway

Hypertension is a condition with chronic elevation of blood pressure and a common preventable risk factor for cardiovascular disease with attendant global morbidity and mortality. The present study investigated the novel antihypertensive action of Naringenin on NƱ‐Nitro‐L‐arginine Methyl Ester (L‐NAME)‐induced hypertension together with possible molecular mechanism of action. Rats were divided into four groups. Rats in Group A were normotensive. The hypertensive group (Group B) received 40 mg/kg) of L‐NAME alone while Groups C and D were concurrently administered Naringenin (50 mg/kg) or Lisinopril (10 mg/Kg) together with L‐NAME orally for 3 weeks. Blood pressure parameters, markers of oxidative stress and renal damage were measured. The immunohistochemistry of kidney injury molecule 1, mineralocorticoid receptor and angiotensin converting enzyme were also determined. Results indicated significant increase in oxidative stress markers and decrease in serum nitric oxide bioavailability in hypertensive rats. Furthermore, there were significant increases in serum myeloperoxidase activity, urinary creatinine, albumin, and blood urea nitrogen levels in hypertensive rats in comparison to hypertensive rats treated with Naringenin. Immunohistochemistry revealed higher expression of kidney injury molecule 1, mineralocorticoid receptor and angiotensin converting enzyme in hypertensive rats. However, co‐treatment with Naringenin mitigated renal oxidative stress, normalized blood pressure and lowered the expression of kidney injury molecule 1, mineralocorticoid receptor, and angiotensin converting enzyme. Combining all, Naringenin offered a novel antihypertensive action through the down regulation of kidney injury molecule 1, deactivation of mineralocorticoid receptor and inhibition of angiotensin converting enzyme.

The Relationship between F2-Isoprostanes Plasma Levels and Depression Symptoms in Healthy Older Adults.

The increasing proportion of older citizens in our society reflects a need to better understand age-related biological underpinnings of mood, as depression in older age may be under-diagnosed. Pre-clinical and human studies evidence a relationship between oxidative stress (OS) biomarkers in depression symptoms, and an influence of biological factors such as Body Mass Index (BMI), but focus has been clinical or younger samples, and less is known about patterns in healthy older adults. We investigated these associations with data derived from the Australian Research Council Longevity Study (ARCLI; ANZCTR12611000487910), in 568 healthy adults aged 60–75 years using F2-Isoprostanes plasma levels, and controlling for demographic factors, in assessing mood via the Beck Depression Inventory-II, Chalder Fatigue Scale, and General Health Questionnaire 12. Elevated F2-Isoprostanes contributed to depressed mood on the BDI-II and reduced general health on the GHQ-12. BMI was positively associated with Chalder Fatigue scores, yet better ratings on the GHQ-12. Females had significantly higher F2-Isoprostanes than males. The results suggest that in otherwise healthy older adults, mood and mental health are reduced with increases in oxidative stress markers, exhibiting similar patterns observed in clinical groups. Sex as a factor should be considered when assessing OS levels in systemic pathologies. BMI as a modifiable risk factor for maintenance of mental health, and OS modification through nutrient supplementation, are discussed. The findings contribute to understanding oxidative stress marker patterns in healthy older adults and their potential role in mood symptoms and mental health.

Sunitinib and Pterostilbene Combination Treatment Exerts Antitumor Effects in Gastric Cancer via Suppression of PDZD8

The use of molecular-targeted drugs in the treatment of gastric cancer is increasing. However, the variety of molecular-targeted drugs in gastric cancer is still limited, and the development of new molecular-targeted therapies is required. The effect of combining sunitinib (SUN) with pterostilbene (PTE) on the human gastric cancer cell lines TMK1 and MKN74 was examined in in vitro and in vivo. Compared with SUN or PTE treatment alone, cotreatment induced pronounced suppression of cell proliferation, with a marked increase in oxidative stress. SUN was associated with a significant retention of mitochondrial Fe2+. SUN-treated cells decreased expression of PDZ domain-containing protein 8 (PDZD8). Knockdown of PDZD8 in both cells induced Fe2+ retention, and siPDZD8+PTE markedly suppressed cell proliferation with suppressed oxidative phosphorylation, as did the combination of SUN+PTE. In a nude mouse tumor model, a pronounced antitumor effect was observed with SUN+PTE treatment compared to SUN alone. PDZD8 may be a newly discovered off-target for SUN, and that the combined use of PTE with SUN significantly promotes antitumor activity in gastric cancer cell lines. The combined use of SUN and PTE might be a new molecular-targeted therapy for gastric cancer.

Elevated serum malondialdehyde (MDA), insulin, follicle-stimulating hormone (FSH), luteinizing hormone (LH), and thyroid- stimulating hormone (TSH), and reduced antioxidant vitamins in polycystic ovarian syndrome patients.

Elevated oxidative stress and hormonal imbalance have been suggested to associate with polycystic ovarian syndromes (PCOS), a causal factor for unsuccessful pregnancy outcomes and other associated complications in women. The aim of this study was to compare the oxidative stress markers and different relevant hormones between pregnant women with and without PCOS. The levels of malondialdehyde (MDA), insulin, follicle- stimulating hormone (FSH), luteinizing hormone (LH), thyroid-stimulating hormone (TSH), vitamin A and vitamin C were measured in 80 pregnant women with PCOS and 80 healthy pregnancies. The mean MDA and insulin levels were significantly elevated in pregnant women with PCOS compared to healthy controls (1.98±0.07 vs. 1.06±0.02 nmol/mL and 11.15±0.25 vs. 6.67±0.25 mIU/L, respectively with p<0.001 for both). Compared to healthy controls, the mean concentrations of FSH (3.65±0.16 vs. 1.75±0.10 IU/L) and LH (15.67±0.63 vs. 3.65±0.16 IU/L) were significantly higher in pregnant women with PCOS, p<0.001 for both comparisons. Similarly, the concentration of serum TSH was also higher in PCOS cases compared to controls (2.79±0.22 vs. 2.34±0.06, p=0.048). In contrast, the levels of vitamin A and C were lower in PCOS cases compared to healthy pregnancy group, 0.45±0.01 vs. 1.05±0.01 and 0.26±0.01 vs. 0.53±0.02, respectively with p-values <0.001 for both comparations. In conclusion, in PCOS cases, serum MDA, insulin, FSH, LH and TSH levels were found to be elevated while the levels of antioxidant vitamins were lower compared to healthy pregnant women. Unusual hormonal imbalance and increase of oxidative stress markers during the pregnancy might be important to establish the PCOS diagnosis.

Targeting of Ubiquitin E3 Ligase RNF5 as a Novel Therapeutic Strategy in Neuroectodermal Tumors.

Simple SummaryNeuroblastoma and melanoma represent two common aggressive tumors of infancy and adulthood, respectively, with the same origin and poor prognosis. Despite the aggressive treatment, advanced neuroblastoma and melanoma patients are often refractory to therapy, relapse and die. Thus, novel therapeutic strategies are urgently needed. In this study, we demonstrated that RNF5, a ubiquitin ligase involved in the degradation of misfolded proteins, was expressed in neuroblastoma and melanoma patients and positively correlated with better outcome. In line with this observation, Analog-1, a pharmacological activator of RNF5, exerted a potent cytotoxic effect on in vitro and in vivo neuroblastoma and melanoma models by modulating the metabolism, reducing the growth and inducing the death of tumor cells. This study is of high translational relevance since it validates RNF5 as an innovative drug target and supports the development of novel therapies for neuroblastoma and melanoma patients in order to ameliorate their clinical outcome.RNF5, an endoplasmic reticulum (ER) E3 ubiquitin ligase, participates to the ER-associated protein degradation guaranteeing the protein homeostasis. Depending on tumor model tested, RNF5 exerts pro- or anti-tumor activity. The aim of this study was to elucidate the controversial role of RNF5 in neuroblastoma and melanoma, two neuroectodermal tumors of infancy and adulthood, respectively. RNF5 gene levels are evaluated in publicly available datasets reporting the gene expression profile of melanoma and neuroblastoma primary tumors at diagnosis. The therapeutic effect of Analog-1, an RNF5 pharmacological activator, was investigated on in vitro and in vivo neuroblastoma and melanoma models. In both neuroblastoma and melanoma patients the high expression of RNF5 correlated with a better prognostic outcome. Treatment of neuroblastoma and melanoma cell lines with Analog-1 reduced cell viability by impairing the glutamine availability and energy metabolism through inhibition of F1Fo ATP-synthase activity. This latter event led to a marked increase in oxidative stress, which, in turn, caused cell death. Similarly, neuroblastoma- and melanoma-bearing mice treated with Analog-1 showed a significant delay of tumor growth in comparison to those treated with vehicle only. These findings validate RNF5 as an innovative drug target and support the development of Analog-1 in early phase clinical trials for neuroblastoma and melanoma patients.

Drought Effects on Morpho-Physiological and Biochemical Traits in Persian Oak and Black Poplar Seedlings

In many arid and semi-arid regions, increasing water scarcity pushes woody species to their physiological limits, making strong drought resistance essential for adaptive forest management. Here, we examined morpho-physiological and biochemical drought responses of the forestry-relevant Persian oak (Quercus brantii Lindl.) and black poplar (Populus nigra L.). In a 120-day greenhouse pot experiment, seedlings were subjected to three watering regimes (FC100, FC60, and FC30, indicating percentages of field capacity). Under FC100 conditions, all biomass measures and the total and specific leaf area of oak were significantly greater compared to those of poplar. FC60-exposed poplar seedlings exhibited strong declines in relative water content (RWC; −33%) and carotenoids (−46%) and a surge in electrolyte leakage (EL; +51%), while these parameters did not change significantly in oak. Although both species showed 80% EL under FC30 conditions, poplar suffered more severe drought damage than oak as evidenced by a 65% lower survival, stronger reductions in RWC and total chlorophyll, as well as stronger increases in oxidative stress markers. Accordingly, poplar seedlings displayed a drought-related 56% decline in quality index while only statistically insignificant reductions occurred in oak seedlings. The superior drought resistance of oak seedlings implies economically more viable nursery production and better seedling establishment, suggesting a shift towards Persian oak-dominated forestry in its natural range under future climate projections.

Polystyrene nanoplastics affect seed germination, cell biology and physiology of rice seedlings in-short term treatments: Evidence of their internalization and translocation

Agroecosystems represent more and more a huge long-term sink for plastic compounds which inevitably undergo fragmentation, generating micro- and nano-plastics, with potential adverse effects on soil chemistry and living organisms. The present work was focused on the short-term effects of two different concentrations of polystyrene nanoplastics (PSNPs) (0.1 or 1 g L−1 suspensions) on rice seedlings starting from seed germination, hypothesizing that possible acute effects on seedlings could depend on oxidative damage trigged by PSNPs internalization. As shown by TEM analysis, PSNPs were absorbed by roots and translocated to the shoots, affected root cell ultrastructure, the germination process, seedling growth and root mitotic activity, inducing cytogenetic aberration. Treatments were not correlated with increase in oxidative stress markers, but rather with a different pattern of their localization both in roots and in shoots, impairing H2O2 homeostasis and membrane damage, despite the adequate antioxidant response recorded. The harmful effects of PSNPs on cell biology and physiology of rice seedlings could be caused not only by a direct action by the PSNPs but also by changes in the production/diffusion of ROS at the tissue/cellular level.

Effects of melatonin ingestion on physical performance and biochemical responses following exhaustive running exercise in soccer players.

Antioxidant supplementation has become a common practice among athletes to boost sport achievement. Likewise, melatonin (MEL) has been ingested as an ergogenic aid to improve physical performance. To date, no study has checked whether the multiple beneficial effects of MEL have an outcome during a maximum running exercise until exhaustion. Therefore, the present study aimed to evaluate the effect of MEL ingestion on physical performance and biochemical responses (i.e., oxidative stress) during exhaustive exercise. In a double blind randomized study, thirteen professional soccer players [age: 17.5 ± 0.8 years, body mass: 70.3 ± 3.9 kg, body height: 1.80 ± 0.08 m; maximal aerobic speed (MAS): 16.85 ± 0.63 km/h; mean ± standard deviation], members of a first league squad, performed a running exercise until exhaustion at 100% of MAS, after either MEL or placebo ingestion. Physical performance was assessed, and blood samples were obtained at rest and following the exercise. Compared to placebo, MEL intake prevented the increase in oxidative stress markers (i.e., malondialdehyde), alleviated the alteration of antioxidant status (i.e., glutathione peroxidase, uric acid and total bilirubin) and decreased post-exercise biomarkers of muscle damage (i.e., creatine kinase and lactate dehydrogenase) (p < 0.05). However, physical performance was not affected by MEL ingestion (p > 0.05). In conclusion, acute MEL intake before a maximal running exercise protected athletes from oxidative stress and cellular damage but without an effect on physical performance.

The activation of hypothalamic AMP-activated protein kinase by oxidative stress is related to hyperphagia in diabetic rats.

During diabetes, there are increased blood glucose levels and oxidative stress. The relationship between oxidative stress and the phosphorylation of AMP-activated protein kinase at the hypothalamic level has been little studied. The objective of this study was to analyze the relationship between oxidative stress and AMP-activated protein kinase activation in Wistar rats with hyperphagia and hyperglycemia. Rats at 7, 14, and 28 days with diabetes were used. Control rats were included. Food intake was calculated to determine hyperphagia. The hypothalamus was extracted to evaluate oxidative stress markers by spectrophotometry; phosphorylation of AMP-activated protein kinase, growth hormone receptor 1a, and neuropeptide Y expression were determined by Western blot. There was a significant increase in the consumption of food in the experimental groups. The level of malondialdehyde decreased in the 7-day group (33%) and increased significantly in the 28-day group (90%), glutathione peroxidase activity increased in the 7-day group (70%) and decreased in the 28-day group (34%), and the phosphorylation of AMP-activated protein kinase increased significantly in the 28-day group (86%). Under ex-vivo conditions in animals with 28 days of hyperglycemia, glutathione peroxidase activity increased 195%, the malondialdehyde level decreased 87%, phosphorylation of AMP-activated protein kinase decreased 53%, and growth hormone receptor 1a expression decreased 66%, when treating hyperglycemic hypothalamic tissue with an antioxidant. NPY expression increased in hyperglycemia, and antioxidant treatment did not regulate its expression. The activation of AMP-activated protein kinase is related with an increase in oxidative stress markers in hyperglycemic and hyperphagic rats.

Mitochondrial bioenergetics of astrocytes in Fragile X syndrome: new perspectives on culture conditions and sex effects.

Fragile X syndrome (FXS) is a genetic disorder that is characterized by a range of cognitive and behavioral deficits, including mild-moderate intellectual disability. The disease is characterized by an X-linked mutation of the Fmr1 gene, which causes silencing of the gene coding for fragile X mental retardation protein (FMRP), a translational regulator integral for neurodevelopment. Mitochondrial dysfunction has been recently associated with FXS, with reports of increases in oxidative stress markers, reactive oxygen species, and lipid peroxidation being present in the brain tissue. Astrocytes, a prominent glial cell within the central nervous system (CNS), play a large role in regulating oxidative homeostasis within the developing brain and dysregulation of astrocyte redox balance in FXS, which may contribute to oxidative stress. Astrocyte function and mitochondrial bioenergetics are significantly influenced by oxygen availability and circulating sex hormones; yet, these parameters are rarely considered during in vitro experimentation. Given that the brain normally develops in a range of hypoxic conditions and FXS is a sex-linked genetic disorder, we investigated how different oxygen levels (normoxic vs. hypoxic) and biological sex affected mitochondrial bioenergetics of astrocytes in FXS. Our results demonstrate that both mitochondrial respiration capacity and reactive oxygen species emission are altered with Fmr1 deletion in astrocytes and these changes were dependent upon both sexual dimorphism and oxygen availability.

Relation of biomarkers of inflammation, oxidative stress and fibrosis in patient with atrial fibrillation

Abstract Background Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia in clinical practice. The patogenesis of AF is linked to an inflammatory reaction and oxidative stress that leads to fibrosis of the atria and progression of the disease. However, the role of different biomarkers in patients with AF is poorly defined. The purpose of this study is to define the role of several biomarkers of inflammation, oxidative stress and fibrosis (myeloperoxidase (MPO), high-sensitivity C-reactive protein (hsCRP), galectin-3 (Gal-3), oxidized low-density lipoprotein (oxLDL)) in patients with AF. Methods We included 75 patients with paroxysmal/persistent AF, who were admitted for electrical cardioversion or pulmonary vein isolation. MPO, hsCRP, Gal-3 and oxLDL were measured before the procedures. We compared the results with 75 healthy age-, sex- and blood pressure-matched individuals. Results Patients with AF had higher MPO (77.1 vs 41.7 ng/ml, p&amp;lt;0.001) compared the healthy subjects. There was also significantly higher hsCRP (3.7 vs 1.6 mg/L, p&amp;lt;0.001) and Gal-3 (12.3 vs 10.4 mg/L, p=0.003). No difference in oxLDL levels (78.8 vs 75.3 U/L, p=0.414) were seen (Table 1). MPO (β=0.012, p=0.014), hsCRP (β=0.213, p=0.046), and weight (β=0.037, p=0.006), were independently associated with AF in a logistic regression analysis (Table 2). Conclusions Patients with AF have increased markers of inflammation and fibrosis, whereas no increase in oxidative stress markers was detected. MPO, hsCRP and age weight were independently predictive of AF. These findings support the role of inflammatory and fibrotic mechanisms as important factors in the electrical and structural remodelling progress in the atria of patients with AF. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Estonian Research Council