Increase In Oxidative Stress Levels Research Articles

Specific role of NAD+ biosynthesis reduction mediated mitochondrial dysfunction in vascular endothelial injury induced by chronic intermittent hypoxia.

Cardiovascular diseases (CVD) are prevalent among those with obstructive sleep apnea (OSA) and are the leading cause of death in these individuals. However, due to clinical confounders, the mechanism by which OSA induces CVD is still unclear. Previous studies have shown that chronic intermittent hypoxia (CIH) and high cholesterol diet (HCD) induce distinct characteristics of atherosclerotic plaques, highlighting the specific mechanisms involved in CIH-induced vascular endothelial injury. This study aims to investigate whether nicotinamide adenine dinucleotide (NAD+) biosynthesis reduction-mediated mitochondrial dysfunction is responsible for vascular endothelial injury induced by CIH and to elucidate its specific role in this process. Models were established to stimulate human umbilical vein endothelial cells (HUVECs) with CIH and oxidized low-density lipoprotein (ox-LDL), and the NAD+ biosynthesis-related indicators, such as NAD+ levels and nicotinamide phosphoribosyltransferase (NAMPT) enzyme activity, were measured in this model. Additionally, interventions were performed by supplementing NAD+ levels with nicotinamide mononucleotide (NMN), inhibiting NAD+ synthesis with FK866, and evaluating mitochondrial function, oxidative stress status, vascular constriction and dilation function, and endothelial adhesion function in these models. A comparative study was conducted to assess the effects of these interventions. We found that under CIH conditions, NAMPT enzyme activity was inhibited, leading to a reduction in NAD+ biosynthesis and a decrease in NAD+/NADH ratio. At the same time, CIH caused mitochondrial dysfunction in HUVECs, including a decrease in adenosine triphosphate (ATP) content and mitochondrial membrane potential, as well as the activity of respiratory chain complex I and III, induced an increase in oxidative stress levels in endothelial cells, impaired vascular constriction and dilation function, and significantly increased expression of adhesion factors. The impact of CIH on endothelial cell-related mitochondrial function and endothelial function was restored by supplementing NMN. Although ox-LDL also causes multi-level endothelial injury, it does not involve the NAD+ pathway, as there were no significant changes in the related indicators, and the impaired endothelial function under ox-LDL conditions was not restored by supplementing NMN. CIH-induced vascular endothelial injury may be associated with NAD+ biosynthesis reduction-mediated mitochondrial dysfunction. Supplementing NAD+ precursors to increase its levels may be a potential intervention to ameliorate CIH-induced vascular endothelial injury, while it does not have a significant effect on endothelial injury caused by ox-LDL.

Effect of vincristine on intraocular pressure and tear fluid oxidative stress biomarkers in canine transmissible venereal tumor.

The ocular side effects of cancer chemotherapeutic drugs are relatively uncommon. Nonetheless, the ocular system has a potentially high sensitivity to toxic substances. This study proposed a framework to assess the effect of vincristine chemotherapy on intraocular pressure, tear protein, and oxidative stress in canines with transmissible venereal tumor (TVT). The study group comprised 10 dogs with TVT, whose diagnosis was based on cytology, and all dogs were treated with vincristine for 4 weeks. Each animal was given a complete ophthalmic examination, followed by a standard Schirmer tear test. Before and 20 min after administering vincristine, intraocular pressure (IOP) was measured in the eyes with a noncontact tonometer. At any of the times mentioned, tear samples were collected using the Schirmer test procedure and were subjected to protein analysis-oxidative stress index (OSI), total antioxidant capacity (TAC), total oxidant status (TOS), nitric oxide (NO), and malondialdehyde (MDA) were determined, and standard statistical analysis was applied. No significant differences were found in protein in tears, but mean Pre and Postinjection IOP revealed a significant decrease in the eyes each week. Also, results indicated significant differences in oxidative stress markers: increased OSI, NO, and MDA, and reduced TAC. The importance of an increase in oxidative stress levels in the tears of vincristine-treated patients should be taken seriously, as it appears to play a role in the pathogenesis of eye disease. Therefore, during the treatment weeks prior to prescribing vincristine, eye diseases should be evaluated and considered.

In vivo and molecular docking studies of the pathological mechanism underlying adriamycin cardiotoxicity

Adriamycin (ADR), one of the most effective broad-spectrum antitumor chemotherapeutic agents in clinical practice, is used to treat solid tumors as well as hematological malignancies in adults and children. However, long-term ADR use causes several adverse reactions, including time- and dose-dependent cardiotoxicity, which limit its clinical application. In addition, the mechanism by which ADR induces cardiotoxicity remains unclear. Therefore, we used zebrafish as animal models to evaluate ADR toxicity during embryonic heart development owing to the similarity of this process in zebrafish to that in humans. Exposure of zebrafish embryos to 1.25, 2.5, and 5 mg/L ADR induced abnormal embryonic development, with the occurrence of cardiac malformations, pericardial edema, decreased movement speed and activity, and increased distance between the venous sinus and the arterial bulb (SV-BA). ADR exposure induced dysregulated cardiogenesis during the precardiac mesoderm formation period. We also observed irregular expression of cardiac-related genes, an upregulation of apoptotic gene expression, and a dose-dependent increase in oxidative stress levels. Furthermore, oxidative stress-induced apoptosis exerted deleterious effects on cardiac development in zebrafish embryos, and treatment with astaxanthin (ATX) alleviated these heart defects. ADR- and Wnt pathway-related genes exhibited good energy and spatial matching, and ADR upregulated the Wnt signaling pathway in zebrafish. Moreover, IWR-1 effectively alleviated ADR-induced heart defects. In conclusion, we demonstrated that the toxic effects of ADR on cardiac development in zebrafish embryos could provide a theoretical basis for explaining the pathogenesis of ADR-induced cardiotoxicity, which occurs through the upregulation of oxidative stress and Wnt signaling pathway, as well as its prevention and treatment in humans. These findings will help develop effective treatment strategies to combat ADR-induced cardiotoxicity and broaden the application of ADR for clinical practice.

Comparative analysis of sulfiredoxin and total oxidative stress levels in diabetic individuals with periodontitis: A case-control study.

The delicate balance between oxidative stress and its antioxidant system can be disrupted in diabetes mellitus (DM), making the tissue susceptible to injury. Hence, this case-control study aims to estimate and correlate the gingival tissue sulfiredoxin and crevicular total oxidative stress (TOS) levels in generalized periodontitis Stage II individuals Grade C (PSII) with and without type II DM. A total of 72 individuals were grouped based on their glycosylated hemoglobin (HbA1c) levels and clinical parameters: group I, periodontally healthy non-diabetic (HbA1c<5.7%) (n=24); group II, non-diabetic with PSII (n=24); and group III, diabetic individuals (HbA1c>6.5%) with PSII (n=24). Gingival tissues and crevicular fluid samples were collected. The samples with adequate protein concentrations (n=72) were further estimated for sulfiredoxin and TOS levels by enzyme-linked immunosorbent assay (ELISA) and calorimetric method, respectively. Tissue sulfiredoxin and crevicular TOS levels are increased significantly in the periodontitis group compared to the non-periodontitis group (p<0.001).The tissue sulfiredoxin levels did not vary significantly between the two periodontitis groups (p<0.179). The TOS levels are significantly higher in the diabetic compared to non-diabetic periodontitis group (p<0.001). Correlation statistics showed a significant positive correlation (r=0.65 and p<0.005) between sulfiredoxin and TOS levels in diabetes with PSII group, however, no such significant correlation was observed in the non-diabetic PSII group (r=0.255 and p<0.422). Diabetic individuals showed inadequate sulfiredoxin-mediated antioxidant response to an increase in oxidative stress levels in periodontitis Stage II Grade C individuals.

TRPM2 Oxidation Activates Two Distinct Potassium Channels in Melanoma Cells through Intracellular Calcium Increase.

Tumor microenvironments are often characterized by an increase in oxidative stress levels. We studied the response to oxidative stimulation in human primary (IGR39) or metastatic (IGR37) cell lines obtained from the same patient, performing patch-clamp recordings, intracellular calcium ([Ca2+]i) imaging, and RT-qPCR gene expression analysis. In IGR39 cells, chloramine-T (Chl-T) activated large K+ currents (KROS) that were partially sensitive to tetraethylammonium (TEA). A large fraction of KROS was inhibited by paxilline—a specific inhibitor of large-conductance Ca2+-activated BK channels. The TEA-insensitive component was inhibited by senicapoc—a specific inhibitor of the Ca2+-activated KCa3.1 channel. Both BK and KCa3.1 activation were mediated by an increase in [Ca2+]i induced by Chl-T. Both KROS and [Ca2+]i increase were inhibited by ACA and clotrimazole—two different inhibitors of the calcium-permeable TRPM2 channel. Surprisingly, IGR37 cells did not exhibit current increase upon the application of Chl-T. Expression analysis confirmed that the genes encoding BK, KCa3.1, and TRPM2 are much more expressed in IGR39 than in IGR37. The potassium currents and [Ca2+]i increase observed in response to the oxidizing agent strongly suggest that these three molecular entities play a major role in the progression of melanoma. Pharmacological targeting of either of these ion channels could be a new strategy to reduce the metastatic potential of melanoma cells, and could complement classical radio- or chemotherapeutic treatments.

SRC-3 Deficiency Exacerbates Neurological Deficits in a Mouse Model of Intracerebral Hemorrhage: Role of Oxidative Stress.

Intracerebral hemorrhage (ICH) causes long term neurological abnormality or death. Oxidative stress is closely involved in ICH mediated brain damage. Steroid receptor cofactor 3 (SRC-3), a p160 family member, is widely expressed in the brain and regulates transactivation of Nrf2, a key component of antioxidant response. Our study aims to test if SRC-3 is implicated in ICH mediated brain injury. We first examined levels of SRC-3 and oxidative stress in the brain of mice following ICH and analyzed their correlation. Then ICH was induced in wild type (WT) and SRC-3 knock out mice and how SRC-3 deletion affected ICH induced brain damage, oxidative stress and behavioral outcome was assessed. We found that SRC-3 mRNA and protein expression levels were reduced gradually after ICH induction in WT mice along with an increase in oxidative stress levels. Correlation analysis revealed that SRC-3 mRNA levels negatively correlated with oxidative stress. Deletion of SRC-3 further increased ICH induced brain edema, neurological deficit score and oxidative stress and exacerbated ICH induced behavioral abnormality including motor dysfunction and cognitive impairment. Our findings suggest that SRC-3 is involved in ICH induced brain injury, probably through modulation of oxidative stress.

Alamandine protects against renal ischaemia-reperfusion injury in rats via inhibiting oxidative stress.

This study was to determine whether alamandine (Ala) could reduce ischaemia and reperfusion (I/R) injury of kidney in rats. Renal I/R was induced by an occlusion of bilateral renal arteries for 70 min and a 24-h reperfusion in vivo, and rat kidney proximal tubular epithelial cells NRK52E were exposed to 24 h of hypoxia and followed by 3-h reoxygenation (H/R) in vitro. The elevated serum creatinine (Cr), blood cystatin C (CysC) and blood urea nitrogen (BUN) levels in I/R rats were inhibited by Ala treatment. Tumour necrosis factor alpha (TNF)-α, IL-1β, IL-6, cleaved caspase-3, cleaved caspase-8 and Bax were increased, and Bcl2 was reduced in the kidney of I/R rats, which were reversed by Ala administration. Ala reversed the increase of TNF-α, IL-1β, IL-6, cleaved caspase-3, cleaved caspase-8 and Bax and the decrease of Bcl2 in the H/R NRK52E cells. Ala could also inhibit the increase of oxidative stress levels in the kidney of I/R rats. NADPH oxidase 1 (Nox1) overexpression reversed the improving effects of Ala on renal function, inflammation and apoptosis of I/R rats. These results indicated that Ala could improve renal function, attenuate inflammation and apoptosis in the kidney of I/R rats via inhibiting oxidative stress.

Protective effect of melatonin against herbicides-induced hepatotoxicity in rats.

Exposure to the herbicides Paraquat and Roundup® may cause cell lesions due to an increase in oxidative stress levels in different biological systems, even in the liver. The aim of this study was to analyze the effect of melatonin on liver of rats exposed to herbicides. A total of 35 rats were randomly divided into seven equal-sized groups: control, Paraquat, Roundup®, Paraquat + Roundup®, Paraquat + melatonin, Roundup®+melatonin, and Paraquat + Roundup®+melatonin. Samples of blood and hepatic tissue were collected at the end of the seventh day of exposure and treatment with melatonin. Body weight, hematological parameters, and histopathological, biochemical analyses and determination of oxidative stress levels in liver were evaluated. Body weight was compromised (P<0.01). Alterations of hematologic parameters were significant when compared to control (P<0.001). Biochemically, serum levels of albumin decreased (P<0.001), but serum levels of alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase increased (P<0.001). Histopathology revealed necrotic hepatocytes, portal and central-lobular inflammatory infiltrate, congestion of capillaries. Serum levels of thiobarbituric acid reactive substances were found to be significantly elevated (P<0.05; P<0.001), and serum level of reduced glutathione was significantly lower (P<0.05; P<0.001). The groups treated concomitantly with melatonin revealed results similar to those of the control. However, melatonin acted as a protective agent for the liver against experimentally induced hepatic toxicity, promoting prevention of body weight, oxidative stress, and normalization of hematological and biochemical parameters.

Effects of Propranolol on Growth, Lipids and Energy Metabolism and Oxidative Stress Response of Phaeodactylum tricornutum.

Simple SummaryIn the past two decades, increasing attention has been directed to investigate the incidence and consequences of pharmaceuticals in the aquatic environment. Propranolol is a non-selective β-adrenoceptor blocker used in large quantities worldwide to treat cardiovascular conditions. Diatoms (model organism) exposed to this compound showed evident signs of oxidative stress, a significant reduction of the autotrophic O2 production and an increase in the heterotrophic mitochondrial respiration. Additionally, diatoms exposed to propranolol showed a consumption of its storage lipids. In ecological terms this will have cascading impacts in the marine trophic webs, where these organisms are key elements, through a reduction of the water column oxygenation and essential fatty acid availability to the heterotrophic organisms that depend on these primary producers. In ecotoxicological terms, diatoms photochemical and fatty acid traits showed to be potential good biomarkers for toxicity assessment of diatoms exposed to this widespread pharmaceutical compound.Present demographic trends suggest a rise in the contributions of human pharmaceuticals into coastal ecosystems, underpinning an increasing demand to evaluate the ecotoxicological effects and implications of drug residues in marine risk assessments. Propranolol, a non-selective β-adrenoceptor blocker, is used worldwide to treat high blood pressure conditions and other related cardiovascular conditions. Although diatoms lack β-adrenoceptors, this microalgal group presents receptor-like kinases and proteins with a functional analogy to the animal receptors and that can be targeted by propranolol. In the present work, the authors evaluated the effect of this non-selective β-adrenoceptor blocker in diatom cells using P. tricornutum as a model organism, to evaluate the potential effect of this compound in cell physiology (growth, lipids and energy metabolism and oxidative stress) and its potential relevance for marine ecosystems. Propranolol exposure leads to a significant reduction in diatom cell growth, more evident in the highest concentrations tested. This is likely due to the observed impairment of the main primary photochemistry processes and the enhancement of the mitochondrial respiratory activity. More specifically, propranolol decreased the energy transduction from photosystem II (PSII) to the electron transport chain, leading to an increase in oxidative stress levels. Cells exposed to propranolol also exhibited high-dissipated energy flux, indicating that this excessive energy is efficiently diverted, to some extent, from the photosystems, acting to prevent irreversible photoinhibition. As energy production is impaired at the PSII donor side, preventing energy production through the electron transport chain, diatoms appear to be consuming storage lipids as an energy backup system, to maintain essential cellular functions. This consumption will be attained by an increase in respiratory activity. Considering the primary oxygen production and consumption pathways, propranolol showed a significant reduction of the autotrophic O2 production and an increase in the heterotrophic mitochondrial respiration. Both mechanisms can have negative effects on marine trophic webs, due to a decrease in the energetic input from marine primary producers and a simultaneous oxygen production decrease for heterotrophic species. In ecotoxicological terms, bio-optical and fatty acid data appear as highly efficient tools for ecotoxicity assessment, with an overall high degree of classification when these traits are used to build a toxicological profile, instead of individually assessed.

EFEK EKSTRAK DAUN GAMBIR ( UNCARIA GAMBIR ROXB) TERHADAP TINGKAT STRESS OKSIDATIF DAN EKSPRESI SIRTUIN 3 PADA HIPOKAMPUS MENCIT BETINA MODEL PENUAAN YANG DIINDUKSI D-GALAKTOSA

The aging process must be experienced by all living things, there will be a decrease in the tissue ability to maintain its function so that pathological conditions occur. Some things can cause aging, Free radical factors are external and internal factors that can trigger aging. Induce of d-galactose continuously one of the factors that can increase oxidative stress. This study was design to evaluate the effect of gambir leaf extract on oxidative stress and expression of the sirtuin 3 gene in the hippocampus of female mice induced intraperitoneally by d-galactose 150 mg/kgbb. Researchers conducted a post test only control group study with a sample of 24 female mice aged 10 - 12 weeks with the inclusion criteria an average body weight of 25-35 grams, obtained from the same breeding place, maintained at the same place and time and never as research material. Mice were divided into 4 groups with 6 mice each , group (C) female mice induced only d-galactose 150 mg / kg and in sonde aquabidest 0,1%/body weight, mice induced by d-galactose and sonde gambir leaf extract at a dose of 100 mg / kg bw group (C1), group (C2) 200 mg/kgbw, and 400 mg/kgbw group (C3). Blood samples were collected to determine the increase in oxidative stress levels of malondealdehyde (MDA) through spectrophotometry, and hippocampal tissue collected for PCR method so that the expression of the sirtuin 3 gene can be seen. Increased levels of MDA are associated with increased oxidative stress. This study reported the results of MDA levels were not significant ( p value &lt;0.05). The results of the PCR reported an increase in expression 2 times higher than the control at a dose of gambier leaf extract 200 mg / kgbw&#x0D; Keywords:D-Galactose, Malondealdehid,Sirtuin 3,Cathechin.

Determination of oxidative stress parameters in fluoxetine users

Fluoxetine (FLU), a selective serotonin reuptake inhibitor, is the first line in depression treatment and it is involved in oxidative stress (OE). Thus, this study aimed to analyze the OE parameters in patients diagnosed with depression and treated with FLU. Were evaluated 121 volunteers divided into two groups: 58 fluoxetine users (with major depression) and 63 non-fluoxetine users (control group, without major depression). The OE was evaluated by determining the levels of malondialdehyde (MDA), total antioxidant power (FRAP) and activity of antioxidant enzymes glutathione peroxidase (GPx) and superoxide dismutase (SOD). MDA, FRAP, GPx and SOD were dosed in plasma. The influence of age, smoking, alcoholism, comorbidities, use of another drugs and antioxidants in the OE were evaluated. The results were compared between the groups. In relation to the fluoxetine daily dose, MDA presented higher levels in patients using 20 mg daily FLU when compared to the control group, as well as the activity of the GPx enzyme and the FRAP levels. In this way, the use of fluoxetine may interfere with the OE parameters, causing an increase in OE levels.

Preliminary study on the anti-apoptotic mechanism of Astragaloside IV on radiation-induced brain cells.

With multiple targets and low cytotoxicity, natural medicines can be used as potential neuroprotective agents. The increase in oxidative stress levels and inflammatory responses in the brain caused by radiation affects cognitive function and neuronal structure, and ultimately leads to abnormal changes in neurogenesis, differentiation, and apoptosis. Astragaloside Ⅳ (AS-Ⅳ), one of the main active constituents of astragalus, is known for its antioxidant, antihypertensive, antidiabetic, anti-infarction, anti-inflammatory, anti-apoptotic and wound healing, angiogenesis, and other protective effects. In this study, the mechanism of AS-IV against radiation-induced apoptosis of brain cells in vitro and in vivo was explored by radiation modeling, which provided a theoretical basis for the development of anti-radiation Chinese herbal active molecules and brain health products. In order to study the protective mechanism of AS-IV on radiation-induced brain cell apoptosis in mice, the paper constructed a radiation-induced brain cell apoptosis model, using TUNEL staining, flow cytometry, Western blotting to analyze AS-IV resistance mechanism to radiation-induced brain cell apoptosis. The results of TUNEL staining and flow cytometry showed that the apoptosis rate of radiation group was significantly increased. The results of Western blotting indicated that the expression levels of p-JNK, p-p38, p53, Caspase-9 and Caspase-3 protein, and the ratio of Bax to Bcl-2 in radiation group were significantly increased. There was no significant difference in the expression levels of JNK and p38. After AS-IV treatment, the apoptosis was reduced and the expression of apoptosis related proteins was changed. These data suggested that AS-IV can effectively reduce radiation-induced apoptosis of brain cells, and its mechanism may be related to the phosphorylation regulation of JNK-p38.

Yellow Wine Polyphenolic Compounds prevents Doxorubicin-induced cardiotoxicity through activation of the Nrf2 signalling pathway.

Doxorubicin (DOX) is considered as the major culprit in chemotherapy‐induced cardiotoxicity. Yellow wine polyphenolic compounds (YWPC), which are full of polyphenols, have beneficial effects on cardiovascular disease. However, their role in DOX‐induced cardiotoxicity is poorly understood. Due to their antioxidant property, we have been suggested that YWPC could prevent DOX‐induced cardiotoxicity. In this study, we found that YWPC treatment (30 mg/kg/day) significantly improved DOX‐induced cardiac hypertrophy and cardiac dysfunction. YWPC alleviated DOX‐induced increase in oxidative stress levels, reduction in endogenous antioxidant enzyme activities and inflammatory response. Besides, administration of YWPC could prevent DOX‐induced mitochondria‐mediated cardiac apoptosis. Mechanistically, we found that YWPC attenuated DOX‐induced reactive oxygen species (ROS) and down‐regulation of transforming growth factor beta 1 (TGF‐β1)/smad3 pathway by promoting nuclear factor (erythroid‐derived 2)‐like 2 (Nrf2) nucleus translocation in cultured H9C2 cardiomyocytes. Additionally, YWPC against DOX‐induced TGF‐β1 up‐regulation were abolished by Nrf2 knockdown. Further studies revealed that YWPC could inhibit DOX‐induced cardiac fibrosis through inhibiting TGF‐β/smad3‐mediated ECM synthesis. Collectively, our results revealed that YWPC might be effective in mitigating DOX‐induced cardiotoxicity by Nrf2‐dependent down‐regulation of the TGF‐β/smad3 pathway.

Caffeic acid phenethyl ester, a propolis polyphenolic, attenuates potentially cadmium-induced testicular dysfunction in mice

Cadmium (Cd) as environmental pollutant can induce severe damage, particularly to the testis. This study investigated the effects of Caffeic acid phenethyl ester (CAPE) on testicular dysfunction induced by Cd. Adult mice were intraperitoneally injected with cadmium chloride (CdCl2) with different doses of CAPE pretreatment. After CdCl2 injection, body/testis weight ratio decreased, Cd levels accumulated and zinc levels decreased in testis. Furthermore, Cd intoxication caused a significant increase of oxidative stress levels, antioxidant enzymes activities, and glutathione levels. Interestingly, significant improvements were observed after the administration of CAPE. Our results demonstrated the protective effect of CAPE, linking Cd testicular dysfunction to oxidative stress.

The Effect of Ginseng Treatment on Melted and Frozen Human Sperm Quality

Introduction: Today, freezing method is one of the most common approaches in the treatment of infertility. This is while oxidative stress is a major destructing factor during sperm freezing and thawing. However, antioxidant compounds can play a key role in sperm freezing techniques. Materials and Methods: In this study, 5 groups of sperms were evaluated with and without Ginseng extract and then some parameters were evaluated such as mobility, activity of mitochondrial, amount of reactive oxygen species (ROS) and DNA fragmentation. Results: Findings revealed that the mobility and mitochondrial activity in sperms significantly increased (P≤0.05) in frozen and thawed sperms, which had been treated with 1 mg/mL Ginseng extract compared to the freezing and thawing sperms without Ginseng extract. In addition, the results showed that Ginseng treatment significantly decreased the amount of ROS and DNA fragmentation compared to freezing and thawing in frozen and thawed treatment without Ginseng (P ≤ 0.05). By preventing the increase of oxidative stress levels, Ginseng prevented the reduction of mobility and mitochondria activity of the sperms after freezing and thawing. It also reduced sperm DNA defeat and reduced the production of free radicals. Conclusions: The results of the present study support the hypothesis that Ginseng has positive effects on the sperm quality in cryopreservation process.

Systematic in vivo study of NiO nanowires and nanospheres: biodegradation, uptake and biological impacts

High aspect ratio nanomaterials (NM) have a promising future in medicine and industry as a unique category of NM. Consequently, it is important to evaluate their potential biological side-effects before crediting their use. To understand the mechanisms of degradation, internalisation, and interaction with different biological targets, we used the in vivo model Drosophila melanogaster to obtain a systematic and complete study on high aspect ratio Ni nanowires (NiNW), compared with low aspect ratio Ni nanospheres (NiNS), and NiSO4 as a model of agent releasing nickel ions. The distinguished shape of nanowires showed changes in their characteristics after oral administration until they reached the intestinal lumen, where their diameter decreased significantly. For the first time, we confirmed the internalization of needle-shaped materials via perforation of the intestinal barrier. Moreover, the results showed that D. melanogaster is a valid and effective tool in studies related to magnetic resonance imaging (MRI). Additionally, NiNM induced DNA damage and molecular changes at the gene expression level, in association with increase in oxidative stress levels. Notably, the observed negative effects were related to nickel as a metal rather than to its shape, since the effects induced by the three Ni forms were notably similar. In addition, independent of their form, Ni compounds did not induce toxic or mutagenic impacts. Our Drosophila model can be used to understand different phenomena related to high aspect ratio NM exposure, such as degradation, internalization and interaction with different targets.

N-acetyl cysteine alleviates oxidative stress and protects mice from dilated cardiomyopathy caused by mutations in nuclear A-type lamins gene.

Cardiomyopathy caused by lamin A/C gene (LMNA) mutations (hereafter referred as LMNA cardiomyopathy) is an anatomic and pathologic condition associated with muscular and electrical dysfunction of the heart, often leading to heart failure-related disability. There is currently no specific therapy available for patients that target the molecular pathophysiology of LMNA cardiomyopathy. We showed here an increase in oxidative stress levels in the hearts of mice carrying LMNA mutation, associated with a decrease of the key cellular antioxidant glutathione (GHS). Oral administration of N-acetyl cysteine, a GHS precursor, led to a marked improvement of GHS content, a decrease in oxidative stress markers including protein carbonyls and an improvement of left ventricular structure and function in a model of LMNA cardiomyopathy. Collectively, our novel results provide therapeutic insights into LMNA cardiomyopathy.

Mechanisms of copper stress alleviation in Citrus trees after metal uptake by leaves or roots.

Nutritional disorders caused by copper (Cu) have affected citrus orchards. Since Cu is foliar sprayed as a pesticide to control citrus diseases, this metal accumulates in the soil. Thereby, we evaluated the effects of Cu leaf absorption after spray of different metal sources, as well as roots absorption on growth, nutritional status, and oxidative stress of young sweet orange trees. Two experiments were carried out under greenhouse conditions. The first experiment was set up with varying Cu levels to the soil (nil Cu, 0.5, 2.0, 4.0 and 8.0g of Cu per plant as CuSO4.5H2O), whereas the second experiment with Cu application via foliar sprays (0.5 and 2.0g of Cu per plant) and comparing two metal sources (CuSO4.5H2O or Cu(OH)2). Copper was mainly accumulated in roots with soil supply, but an increase of oxidative stress levels was observed in leaves. On the other hand, Cu concentrations were higher in leaves that received foliar sprays, mainly as Cu(OH)2. However, when sulfate was foliar sprayed, plants exhibited more symptoms of injuries in the canopy with decreased chlorophyll contents and increased hydrogen peroxide and lipid peroxidation levels. Copper toxicity was characterized by sap leakage from the trunk and twigs, which is the first report of this specific Cu excess symptom in woody trees. Despite plants with 8.0g of Cu soil-applied exhibiting the sap leakage, growth of new plant parts was more vigorous with lower oxidative stress levels and injuries compared to those with 4.0g of Cu soil-applied (without sap leakage). With the highest level of Cu applied via foliar as sulfate, Cu was eliminated by plant roots, increasing the rhizospheric soil metal levels. Despite citrus likely exhibiting different mechanisms to reduce the damages caused by metal toxicity, such as responsive enzymatic antioxidant system, metal accumulation in the roots, and metal exclusion by roots, excess Cu resulted in damages on plant growth and metabolism when the metal was taken up either by roots or leaves.

Effects of melatonin in rats in the initial third stage of pregnancy exposed to sub-lethal doses of herbicides

Exposure to the herbicides Paraquat (PQ) and Roundup® may cause cell lesions due to an increase in oxidative stress levels in different biological systems, even in the reproductive system. ObjectiveEvaluate the possible changes in reproductive parameters and hepatic, as well as its prevention by simultaneous application of melatonin. MethodsThirty-five female rats at the age of 3 months were divided into seven groups: three groups exposed to sub-lethal doses of the herbicides PQ (50mg/kg) and Roundup® (500mg/kg) (n=5, G2, G3 and G4); three groups exposed to herbicides and simultaneous treatment with 10mg/kg of Melatonin (n=5, G5, G6 and G7) and control group (n=5, G1) from the first to the seventh day of pregnancy. On the seventh day of pregnancy, the rats were anesthetized and euthanized, followed by laparotomy to remove their reproductive tissues and liver. Body and ovary weights were taken and the number of implantation sites, corpora lutea, preimplantation losses, implantation rates were counted and histopathology of the implantation sites, morphometry of the surface and glandular epithelia of endometrium and hepatic oxidative stress were undertaken. ResultsThe present study shows the decrease in body and ovary weight, decrease in the number of implantation sites, implantation rate, in the total number of corpora lutea and increase of preimplantation percentages were observed when compared to the G1: Fig. 1 and Table 1, (p>0.001 ANOVA/Tukey). The histopathological analysis of the implantation sites showed a disorder of the cytotrophoblast and cell degeneration within the blastocyst cavity in Fig. 4. Morphometry revealed a reduction in surface and glandular epithelia and in the diameter of the endometrial glands (Table 2; p>0.05 ANOVA/Tukey), whereas in liver, serum levels of thiobarbituric acid reactive substances (TBARS) were found to be significantly elevated (Fig. 2; p>0.001; p>0.05 ANOVA/Tukey), and serum level of reduced glutathione (GSH) was significantly lower (Fig. 3; p>0.001 ANOVA/Tukey). However, treatments with melatonin exhibited improvements in reproductive parameters, as well as reduced lesions in the implantation sites (Fig. 4.) and in serum levels TBARS (Fig. 2; p>0.001 ANOVA/Tukey), serum levels GSH (Fig. 3; p>0.001; p>0.05 ANOVA/Tukey). ConclusionsThese results reveal that melatonin is a protective agent against experimentally induced maternal/embryo toxicity with herbicides and favoring normalization of reproductive parameters and hepatic.

To find the role of DNA damage marker 8-hydroxy 2-deoxy guanosine in patients of prostate cancer, benign prostatic hyperplasia and its association to other prognostic factors of prostate cancer

Purpose: The aim of the study was to identify correlation between DNA damage marker 8-hydroxy 2-deoxy guanosine (8-OHdG) and other prognostic factors such as Gleason's score, serum prostate-specific antigen (PSA), and stage in carcinoma prostate and to assess a probability-correlation between DNA damage and benign prostatic hyperplasia (BPH) and control. Materials and Methods: A study has been carried out prospectively. Forty patients of carcinoma prostate, 34 BPH, and 14 healthy controls were included in the study between the period of July 2010 to July 2012. Serum 8-OHdG level was measured in all subjects as a marker of DNA damage. Results: Serum 8-OHdG level was significantly raised in patient with prostate cancer (313.39 ± 69.48 ng/mL) as compared with BPH patients (204.42 ± 40.97 ng/mL) and control group (198.94 ± 15.74 ng/mL) with P 20 ng/mL, Gleason's score >6 had higher mean 8-OHdG levels as compared to serum PSA ≤20 and Gleason score ≤6, as P< 0.05. There was also direct association found between prostate volume and stage of the tumor though it was not significant. Conclusions: These findings suggest that oxidative stress level was significantly raised in prostate cancer patients. It was also observed that a significant direct association exists between oxidative stress and certain clinicopathologic factors, including serum PSA, Gleason score, and metastasis which show that with progression of disease, there was increase in oxidative stress level.