Beneficial Effects of Fibroblast Growth Factor-1 on Retinal Pigment Epithelial Cells Exposed to High Glucose-Induced Damage: Alleviation of Oxidative Stress, Endoplasmic Reticulum Stress, and Enhancement of Autophagy.

Diabetic retinopathy (DR) severely affects vision in individuals with diabetes. High glucose (HG) induces oxidative stress in retinal cells, a key contributor to DR development. Previous studies suggest that fibroblast growth factor-1 (FGF-1) can mitigate hyperglycemia and protect tissues from HG-induced damage. However, the specific effects and mechanisms of FGF-1 on DR remain unclear. In our study, FGF-1-pretreated adult retinal pigment epithelial (ARPE)-19 cells were employed to investigate. Results indicate that FGF-1 significantly attenuated HG-induced oxidative stress, including reactive oxygen species, DNA damage, protein carbonyl content, and lipid peroxidation. FGF-1 also modulated the expression of oxidative and antioxidative enzymes. Mechanistic investigations showed that HG induced high endoplasmic reticulum (ER) stress and upregulated specific proteins associated with apoptosis. FGF-1 effectively alleviated ER stress, reduced apoptosis, and restored autophagy through the adenosine monophosphate-activated protein kinase/mammalian target of the rapamycin signaling pathway. We observed that the changes induced by HG were dose-dependently reversed by FGF-1. Higher concentrations of FGF-1 (5 and 10 ng/mL) exhibited increased effectiveness in mitigating HG-induced damage, reaching statistical significance (p < 0.05). In conclusion, our study underscores the promising potential of FGF-1 as a safeguard against DR. FGF-1 emerges as a formidable intervention, attenuating oxidative stress, ER stress, and apoptosis, while concurrently promoting autophagy. This multifaceted impact positions FGF-1 as a compelling candidate for alleviating retinal cell damage in the complex pathogenesis of DR.

Differential intestinal effects of water and foodborne exposures of nano-TiO2 in the mussel Mytilus coruscus under elevated temperature.

With the wide use of nanomaterials in daily life, nano-titanium dioxide (nano-TiO2) presents potential ecological risks to marine ecosystems, which can be exacerbated by ocean warming (OW). However, most previous studies have only centered around waterborne exposure, while there is a scarcity of studies concentrating on the impact of trophic transfer exposure on organisms. We investigated the differences in toxic effects of 100 µg/L nano-TiO2 on mussels via two pathways (waterborne and foodborne) under normal (24 °C) and warming (28 °C) conditions. Single nano-TiO2 exposure (waterborne and foodborne) elevated the superoxide dismutase (SOD) and catalase (CAT) activities as well as the content of glutathione (GSH), indicating activated antioxidatant response in the intestine. However, depressed antioxidant enzymes and accumulated peroxide products (LPO and protein carbonyl content, PCC) demonstrated that warming in combination with nano-TiO2 broke the prooxidant-antioxidant homeostasis of mussels. Our findings also indicated that nano-TiO2 and high temperature exhibited adverse impacts on amylase (AMS), trypsin (PS), and trehalase (THL). Additionally, activated immune function (lysozyme) comes at the cost of energy expenditure of protein (decreased protein concentration). The hydrodynamic diameter of nano-TiO2 at 24 °C (1693-2261 nm) was lower than that at 28 °C (2666-3086 nm). Bioaccumulation results (range from 0.022 to 0.432 µg/g) suggested that foodborne induced higher Ti contents in intestine than waterborne. In general, the combined effects of nano-TiO2 and warming demonstrated a more pronounced extent of interactive effects and severe damage to antioxidant, digestive, and immune parameters in mussel intestine. The toxicological impact of nano-TiO2 was intensified through trophic transfer. The toxic effects of nano-TiO2 are non-negligible and can be exerted together through both water- and foodborne exposure routes, which deserves further investigation.

Environmental factors influence cross-talk between a heat shock protein and an oxidative stress protein modification in the lizard Gallotia galloti.

Better understanding how organisms respond to their abiotic environment, especially at the biochemical level, is critical in predicting population trajectories under climate change. In this study, we measured constitutive stress biomarkers and protein post-translational modifications associated with oxidative stress in Gallotia galloti, an insular lizard species inhabiting highly heterogeneous environments on Tenerife. Tenerife is a small volcanic island in a relatively isolated archipelago off the West coast of Africa. We found that expression of GRP94, a molecular chaperone protein, and levels of protein carbonylation, a marker of cellular stress, change across different environments, depending on solar radiation-related variables and topology. Here, we report in a wild animal population, cross-talk between the baseline levels of the heat shock protein-like GRP94 and oxidative damage (protein carbonylation), which are influenced by a range of available temperatures, quantified through modelled operative temperature. This suggests a dynamic trade-off between cellular homeostasis and oxidative damage in lizards adapted to this thermally and topologically heterogeneous environment.

α-bisabolol ß-d-fucopyranoside (ABFP) ameliorates scopolamine-induced memory deficits through cholinesterase inhibition and attenuation of oxidative stress in zebrafish (Danio rerio).

Alzheimer's disease (AD) is one of the major devastating neurodegenerative disorders associated with the gradual decline of an individual's memory, cognition, and ability to carry out day-to-day activities. In the present study, the neuroprotective ability of α-bisabolol ß-d-fucopyranoside (ABFP) was assessed via measurement of antioxidant parameters like lipid peroxidation, glutathione peroxidation, glutathione, protein carbonyl content assays, and caspase-3 activity estimation. Moreover, the acute toxicity of ABFP was estimated in the zebrafish larval model. The results showed that ABFP exhibits little to no toxicity at lower concentrations in the acute toxicity test. ABFP-pretreated and scopolamine-exposed fish exhibited more exploratory behavior in the behavior assay than scopolamine-only induced groups. Additionally, the results of antioxidant enzyme assays revealed reduced oxidative stress and damage in ABFP-treated fish, while enzyme activity experiments carried out with brain homogenate from ABFP-treated fish showed decreased acetylcholinesterase enzyme activity. Overall, it can be concluded that ABFP has the potential to be a promising agent for the treatment of AD in the future.

Dietary supplementation of ark clams protects gut health and modifies gut microbiota in d-galactose-induced aging rats.

BACKGROUND: Ark clams, a seafood abundant in various nutrients, are widely consumed worldwide. This study aimed to investigate the protective benefits of two common ark clams in Korea, Scapharca subcrenata (SS) and Tegillarca granosa (TG), on gut health in d-galactose (d-gal)-induced aging rats. RESULTS: Thirty-two Wistar rats (11 weeks old) were randomly allocated into four groups: a CON group (normal diet + saline intraperitoneal (i.p.) injection), a CD group (normal diet + d-gal i.p. injection), an SS group (normal diet with 5% SS supplementation + d-gal i.p. injection), and a TG group (normal diet with 5% TG supplementation + d-gal i.p. injection). After 12 weeks of treatment, histopathological results showed that gut barrier damage was alleviated in rats of the SS and TG groups, as evidenced by increases in mucus layer thickness and goblet cell numbers. Meanwhile, the two groups supplemented with ark clams showed an evident reduction in oxidative stress biomarkers (malondialdehyde and protein carbonyl content levels in the colon) and an increase in the immune-related factor (immunoglobulin A level in the plasma) in rats. The 16S ribosomal RNA analysis revealed that SS and TG ark clams significantly increased the proliferations of Bacteroidetes at the phylum level and Parabacteroides at the genus level. Additionally, the levels of the three main short-chain fatty acids in the cecal contents were also significantly increased in the SS and TG groups. CONCLUSION: Our results indicated a potent preventive effect of SS and TG ark clams on d-gal-induced gut injury, suggesting that ark clams may be a promising dietary component for intervening in aging. © 2023 Society of Chemical Industry.

Evaluation of Bis(2-ethylhexyl) phthalate toxicity on the third instar larvae of transgenic Drosophila melanogaster (hsp70-lacZ) Bg9.

Bis(2-ethylhexyl) phthalate, generally known as DEHP is a synthetic compound mainly used as a plasticizer to make polyvinyl chloride products flexible and soft. The present work aimed to study the toxicity of Bis(2-ethylhexyl) phthalate on the third instar larvae of transgenic Drosophila melanogaster(hsp70-lacZ) Bg9. The hsp70 gene is associated with the ß-galactosidase in our present transgenic strain therefore, the more activity of ß-galactosidase will indirectly correspond to hsp70 expression. The third instar larvae were allowed to feed on the diet for 24 h having 0.001, 0.005, 0.01, and 0.02 M of Bis(2-ethylhexyl) phthalate at the final concentration. After the exposure of 24hrs, the larvae were subjected to ONPG assay, X-gal staining, trypan blue exclusion test, oxidative stress markers assays, and comet assay. A dose-dependent increase in hsp70 expression, tissue damage, Glutathione-S-transferase (GST) activity, lipid peroxidation, monoamine oxidase, caspase-9 & 3, protein carbonyl content (PCC), DNA damage and decrease in the glutathione (GSH) content, delta-aminolevulinic acid dehydrogenase (ẟ-ALD-D) and acetylcholinesterase activity were observed in the larvae exposed to 0.005, 0.01, 0.02 M of Bis-(2-ethylhexyl) phthalate. The dose of 0.001 M of Bis(2-ethylhexyl) phthalate did not showed any toxic effects and hence can be considered as No Observed Adverse Effect Level (NOAEL) for Bis(2-ethylhexyl) phthalate. The study supports the use of Drosophila for the evaluation of possible toxic effects associated with synthetic compounds.

Elevated Plasma Protein Carbonyl Concentration Is Associated with More Abnormal White Matter in People with HIV.

Structural brain abnormalities, including those in white matter (WM), remain common in people with HIV (PWH). Their pathogenesis is uncertain and may reflect multiple etiologies. Oxidative stress is associated with inflammation, HIV, and its comorbidities. The post-translational carbonylation of proteins results from oxidative stress, and circulating protein carbonyls may reflect this. In this cross-sectional analysis, we evaluated the associations between protein carbonyls and a panel of soluble biomarkers of neuronal injury and inflammation in plasma (N = 45) and cerebrospinal fluid (CSF, n = 32) with structural brain MRI. The volume of abnormal WM was normalized for the total WM volume (nAWM). In this multisite project, all regression models were adjusted for the scanner. The candidate covariates included demographics, HIV disease characteristics, and comorbidities. Participants were PWH on virally suppressive antiretroviral therapy (ART) and were mostly white (64.4%) men (88.9%), with a mean age of 56.8 years. In unadjusted analyses, more nAWM was associated with higher plasma protein carbonyls (p = 0.002) and higher CCL2 (p = 0.045). In the adjusted regression models for nAWM, the association with plasma protein carbonyls remained significant (FDR p = 0.018). Protein carbonyls in plasma may be a valuable biomarker of oxidative stress and its associated adverse health effects, including within the central nervous system. If confirmed, these findings would support the hypothesis that reducing oxidative stress could treat or prevent WM injury in PWH.

A novel two-way rebalancing strategy for identifying carbonylation sites.

BACKGROUND: As an irreversible post-translational modification, protein carbonylation is closely related to many diseases and aging. Protein carbonylation prediction for related patients is significant, which can help clinicians make appropriate therapeutic schemes. Because carbonylation sites can be used to indicate change or loss of protein function, integrating these protein carbonylation site data has been a promising method in prediction. Based on these protein carbonylation site data, some protein carbonylation prediction methods have been proposed. However, most data is highly class imbalanced, and the number of un-carbonylation sites greatly exceeds that of carbonylation sites. Unfortunately, existing methods have not addressed this issue adequately. RESULTS: In this work, we propose a novel two-way rebalancing strategy based on the attention technique and generative adversarial network (Carsite_AGan) for identifying protein carbonylation sites. Specifically, Carsite_AGan proposes a novel undersampling method based on attention technology that allows sites with high importance value to be selected from un-carbonylation sites. The attention technique can obtain the value of each sample's importance. In the meanwhile, Carsite_AGan designs a generative adversarial network-based oversampling method to generate high-feasibility carbonylation sites. The generative adversarial network can generate high-feasibility samples through its generator and discriminator. Finally, we use a classifier like a nonlinear support vector machine to identify protein carbonylation sites. CONCLUSIONS: Experimental results demonstrate that our approach significantly outperforms other resampling methods. Using our approach to resampling carbonylation data can significantly improve the effect of identifying protein carbonylation sites.

Protein Carbonylation Contributes to Prothrombotic Fibrin Clot Phenotype in Acute Ischemic Stroke: Clinical Associations.

BACKGROUND: Acute ischemic stroke (AIS) is associated with enhanced oxidative stress and unfavorably altered fibrin clot properties. We investigated determinants of plasma protein carbonylation (PC) in AIS, its impact on the prothrombotic state, and prognostic value during follow-up. METHODS: We included 98 consecutive AIS patients aged 74±12 years (male:female ratio, 50:48 [51%:49%]) at the Neurology Center in Warsaw, Poland, between January and December 2014. As many as 74 (75.5%) patients underwent thrombolysis, and 24 were unsuitable for thrombolysis. We determined plasma PC, along with thrombin generation, fibrin clot permeability, and clot lysis time on admission, at 24 hours, and 3 months. Stroke severity was assessed using the National Institutes of Health Stroke Scale and stroke outcome with the modified Rankin Scale. Hemorrhagic transformation was assessed on the computed tomography scan within 48 hours from the symptom onset, while stroke-related mortality was evaluated at 3 months. RESULTS: On admission, PC levels (median, 4.61 [3.81-5.70] nM/mg protein) were associated with the time since symptom onset (r=0.41; P<0.0001) and with the National Institutes of Health Stroke Scale score (P=0.36; P=0.0003). Higher PC levels on admission correlated with denser fibrin clot formation and prolonged clot lysis time but not with thrombin generation. In thrombolysed patients, lower PC levels were observed after 24 hours (-34%) and at 3 months (-23%; both P<0.001). PC levels at baseline and after 24 hours predicted the modified Rankin Scale score >2 at 3 months (OR, 1.90 [95% CI, 1.21-3.00]; OR, 2.19 [95% CI, 1.39-3.44], respectively). Higher PC at baseline predicted hemorrhagic transformation of stroke (OR, 1.95 [95% CI, 1.02-3.74]) and stroke-related mortality (OR, 2.02 [95% CI, 1.08-3.79]), while higher PC at 24 hours predicted solely stroke-related mortality (OR, 2.11 [95% CI, 1.28-3.46]). CONCLUSIONS: Elevated plasma PC levels in patients with AIS, related to prothrombotic fibrin clot properties, are associated with stroke severity. Thrombolysis reduces the extent of PC. The current study suggests a prognostic value of PC in AIS.

Effects of unpredictable chronic mild stress on the cellular redox state and mitochondrial energy homeostasis in rat adipose tissue: A comprehensive metabolic study.

Unpredictable chronic mild stress (UCMS) leads to variable metabolic effects. Oxidative stress (OS) of adipose tissue (AT) and mitochondrial energy homeostasis is little investigated. This work studied the effects of UCMS on OS and the antioxidant/redox status in AT and mitochondrial energy homeostasis in rats. Twenty-four male Wistar rats (180-220 g) were divided into two equal groups; the normal control (NC) group and the UCMS group which were exposed to various stresses for 28 days. An indirect calorimetry machine was used to measure volumes of respiratory gases (VO2 & VCO2 ), total energy expenditure (TEE), and food intake (FI). The AT depots were collected, weighed, and used for measuring activities and gene expression of key antioxidant enzymes (GPx1, SOD, CAT, GR, GCL, and GS), OS marker levels including superoxide anion (SA), peroxynitrite radical (PON), nitric oxide (NO), hydrogen peroxide (H2 O2 ), lipid peroxides (LPO), t-protein carbonyl content (PCC), and reduced/oxidized glutathione levels (GSH, GSSG). Additionally, AT mitochondrial fractions were used to determine the activities of the tricarboxylic acid cycle (TCA) cycle enzymes (CS, α-KGDH, ICDH, SDH, MDH), respiratory chain complexes I-III, II-III, IV, the nicotinamide coenzymes NAD+ , NADH, and ATP/ADP levels. Compared with the NC group, the UCMS group showed very significantly increased OS marker levels, lowered antioxidant enzyme activities and gene expression, as well as lowered TCA cycle and respiratory chain activity and NAD+ , NADH, and ATP levels (p < .001 for all comparisons). Besides, the UCMS group had lowered TEE and insignificant FI and weight gain. In conclusion, AT of the UCMS-subjected rats showed a state of disturbed redox balance linked to disrupted energy homeostasis producing augmentation of AT.

Protein carbonylation and structural changes in porcine myofibrillar protein exposed to metal ion-H2O2-ascorbate and linoleic acid-lipoxidase oxidizing systems.

The present study aimed to compare two oxidizing systems commonly present in meat for their influence on protein oxidation patterns, with emphasis on the specific lysine-derived markers for protein carbonylation (α-aminoadipic semialdehyde, AAS; lysinonorlucine, LNL) and their relationships with the common markers for protein oxidation. For this purpose, pork myofibrillar proteins (MFP, 5 mg/mL) were suspended in 0.6 M NaCl (pH 7.5) and incubated at 4 ℃ for 24 h with two oxidizing systems: (1) a metal-catalyzed oxidizing system (MOS: 10 µM FeCl3, 100 µM ascorbic acid, and 0-10 mmol/L H2O2), (2) a linoleic acid - lipoxidase oxidizing system (LOS: 7500 units of lipoxidase/mL, and 0-10 mM linoleic acid). Results showed that the amounts of AAS and LNL in both MOS- and LOS-oxidized MFP was proportional to the oxidant concentrations (H2O2 or linoleic acid), while the formation of total carbonyl and total thiol also exhibited similar oxidant-dose-dependent patterns. Meanwhile, the α-helix contents of MFP declined with oxidant concentrations irrespective of the oxidizing systems. The reducing SDS-PAGE revealed that the myosin heavy chain band started to diminish at high H2O2 concentration (5 and 10 mM) in MOS whereas at low level of linoleic acid (0.5 mM) in LOS. Overall, these results demonstrated both oxidizing systems could be involved in the formation of AAS and LNL, and that the generation of AAS and LNL can be used as reliable markers for protein oxidation, but also might be directly involved in protein structural changes and then contribute to the alternations of protein functionality.

Calpain inhibition decreases oxidative stress via mitochondrial regulation in a swine model of chronic myocardial ischemia.

INTRODUCTION: Calpain overexpression is implicated in mitochondrial damage leading to tissue oxidative stress and myocardial ischemic injury. The aim of this study was to determine the effects of calpain inhibition (CI) on mitochondrial impairment and oxidative stress in a swine model of chronic myocardial ischemia and metabolic syndrome. METHODS: Yorkshire swine were fed a high-fat diet for 4 weeks to induce metabolic syndrome then underwent placement of an ameroid constrictor to the left circumflex artery. Three weeks later, animals received: no drug (control, "CON"; n= 7); a low-dose calpain inhibitor (0.12 mg/kg; "LCI", n= 7); or high-dose calpain inhibitor (0.25 mg/kg; "HCI", n=7). Treatment continued for 5 weeks, followed by tissue harvest. Cardiac tissue was assayed for protein carbonyl content, as well as antioxidant and mitochondrial protein expression. Reactive oxygen species (ROS) and mitochondrial respiration was measured in H9c2 cells following exposure to normoxia or hypoxia (1%) for 24 h with or without CI. RESULTS: In ischemic myocardial tissue, CI was associated with decreased total oxidative stress compared to control. CI was also associated with increased expression of mitochondrial proteins superoxide dismutase 1, SDHA, and pyruvate dehydrogenase compared to control. 100 nM of calpain inhibitor decreased ROS levels and respiration in both normoxic and hypoxic H9c2 cardiomyoblasts. CONCLUSIONS: In the setting of metabolic syndrome, CI improves oxidative stress in chronically ischemic myocardial tissue. Decreased oxidative stress may be via modulation of mitochondrial proteins involved in free radical scavenging and production.

Effect of trehalose on miR-132 and SIRT1 in the hippocampus of aged rats.

Aging causes substantial molecular to morphological changes in the brain. The brain cells are more susceptible towards oxidative damage due to impaired antioxidant defense system. Sirtuin1 (SIRT1) is a crucial cellular survival protein, which its gene has been identified as a direct target of microRNA 132 (miR-132). Trehalose contributes to preventing neuronal damage through several mechanisms. However, little is known about the interactive effects of aging and trehalose on the expression pattern of miR-132 and SIRT1 in the hippocampus. Male Wistar rats were divided into four groups. Two groups of aged (24 months) and young (4 months) rats were administered 2% trehalose solution for 30 days. Two other groups of aged and young rats received regular tap water. At the end of treatment, the levels of Sirt1 mRNA and its protein, malondialdehyde, protein carbonyl content, total antioxidant capacity, tumor necrosis factor α (TNF-α), as well as the expression of miR-132 were measured in the hippocampus. We found that trehalose treatment upregulated the expression of SIRT1 and miR-132. Moreover, administration of trehalose enhanced the level of total antioxidant activity whereas reduced the levels of lipid peroxidation, protein carbonyl content, and TNF-α. In conclusion, our data indicated that trehalose restored antioxidant status and alleviated inflammation in the hippocampus which was probably associated with the upregulation of SIRT1 and miR-132.

Selenate triggers diverse oxidative responses in Astragalus species with diverse selenium tolerance and hyperaccumulation capacity.

Selenium (Se) hyperaccumulators are capable of uptake and tolerate high Se dosages. Excess Se-induced oxidative responses were compared in Astragalus bisulcatus and Astragalus cicer. Plants were grown on media supplemented with 0, 25 or 75 µM selenate for 14 days. Both A. bisulcatus and A. cicer accumulated >2000 µg/g dry weight Se to the shoot but the translocation factors of A. cicer were below 1 suggesting its non hyperaccumulator nature. A. cicer showed Se sensitivity indicated by reduced seedling fresh weight, root growth and root apical meristem viability, altered element homeostasis in the presence of Se. In Se-exposed A. bisulcatus, less toxic organic Se forms (mainly MetSeCys, γ-Glu-MetSeCys, and a selenosugar) dominated, while these were absent from A. cicer suggesting that the majority of the accumulated Se may be present as inorganic forms. The glutathione-dependent processes were more affected, while ascorbate levels were not notably influenced by Se in either species. Exogenous Se triggered more intense accumulation of malondialdehyde in the sensitive A. cicer compared with the tolerant A. bisulcatus. The extent of protein carbonylation in the roots of the 75 µM Se-exposed A. cicer exceeded that of A. bisulcatus indicating a correlation between selenate sensitivity and the degree of protein carbonylation. Overall, our results reveal connection between oxidative processes and Se sensitivity/tolerance/hyperaccumulation and contribute to the understanding of the molecular responses to excess Se.

Green Synthesised TiO2 Nanoparticles-Mediated Terenna asiatica: Evaluation of Their Role in Reducing Oxidative Stress, Inflammation and Human Breast Cancer Proliferation.

Oxidative stress and chronic inflammation interplay with the pathogenesis of cancer. Breast cancer in women is the burning issue of this century, despite chemotherapy and magnetic therapy. The management of secondary complications triggered by post-chemotherapy poses a great challenge. Thus, identifying target-specific drugs with anticancer potential without secondary complications is a challenging task for the scientific community. It is possible that green technology has been employed in a greater way in order to fabricate nanoparticles by amalgamating plants with medicinal potential with metal oxide nanoparticles that impart high therapeutic properties with the least toxicity. Thus, the present study describes the synthesis of Titanium dioxide nanoparticles (TiO2 NPs) using aqueous Terenna asiatica fruit extract, with its antioxidant, anti-inflammatory and anticancer properties. The characterisation of TiO2 NPs was carried out using a powdered X-ray diffractometer (XRD), Fourier transform infrared (FTIR), scanning electron microscopy (SEM), energy-dispersive X-ray diffraction (EDX), high-resolution transmission electron microscopy (HR-TEM), dynamic light scattering (DLS), and zeta-potential. TiO2 NPs showed their antioxidant property by scavenging 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radicals in a dose-dependent manner with an IC50 value of 80.21 µg/µL. To ascertain the observed antioxidant potential of TiO2 NPs, red blood cells (RBC) were used as an in vitro model system. Interestingly, TiO2 NPs significantly ameliorated all the stress parameters, such as lipid peroxidation (LPO), protein carbonyl content (PCC), total thiol (TT), superoxide dismutase (SOD), and catalase (CAT) in sodium nitrite (NaNO2)-induced oxidative stress, in RBC. Furthermore, TiO2 NPs inhibited RBC membrane lysis and the denaturation of both egg and bovine serum albumin, significantly in a dose-dependent manner, suggesting its anti-inflammatory property. Interestingly, TiO2 NPs were found to kill the MCF-7 cells as a significant decrease in cell viability of the MCF-7 cell lines was observed. The percentage of growth inhibition of the MCF-7 cells was compared to that of untreated cells at various doses (12.5, 25, 50, 100, and 200 µg/mL). The IC50 value of TiO2 NPs was found to be (120 µg/mL). Furthermore, the Annexin V/PI staining test was carried out to confirm apoptosis. The assay indicated apoptosis in cancer cells after 24 h of exposure to TiO2 NPs (120 µg/mL). The untreated cells showed no significant apoptosis in comparison with the standard drug doxorubicin. In conclusion, TiO2 NPs potentially ameliorate NaNO2-induced oxidative stress in RBC, inflammation and MCF-7 cells proliferation.

Sub­chronic administration of lead alters markers of oxidative stress, acetylcholinesterase and Na+K+­ATPase activities in rat brain.

This study investigated the effects of sub­chronic administration of lead (Pb) acetate on thiobarbituric acid reactive substances (TBA­RS), total sulfhydryl content, protein carbonyl content, antioxidant enzymes (superoxide dismutase [SOD], catalase [CAT], glutathione peroxidase [GSH­Px]), acetylcholinesterase (AChE), and Na+K+­ATPase in the cerebral structures of rats. Male Wistar rats aged 60 days were treated with saline (control group) or Pb (treatment group), at various doses, by gavage, once a day for 35 days. The animals were sacrificed twelve hours after the last administration, and the cerebellum, hippocampus and cerebral cortex were removed. The results showed that Pb did not alter the evaluated oxidative stress parameters. Furthermore, Pb (64 and/or 128 mg/kg) altered SOD in the cerebellum, cerebral cortex and hippocampus. Pb (128 mg/kg) altered CAT in the cerebellum and cerebral cortex and GSH­Px in the cerebral cortex. Also, Pb (64 mg/kg and 128 mg/kg) altered GSH­Px in the cerebellum. Moreover, Pb (128 mg/kg) increased AChE in the hippocampus and decreased Na+K+­ATPase in the cerebellum and hippocampus. In conclusion, sub­chronic exposure to Pb (occupational and environmental intoxication) altered antioxidant enzymes, AChE, and Na+K+­ATPase, contributing to cerebral dysfunction.

Increased circulating levels of MIP-1α and CD14 are associated with the presence of severe stenosis and hypoechoic plaques in patients with carotid atherosclerosis.

OBJECTIVE: Carotid atherosclerosis, a major cause of ischemic cerebrovascular events, is characterized by a pro-inflammatory and pro-oxidant vascular microenvironment. The current risk score models based on traditional risk factors for cardiovascular risk assessment have some limitations. The identification of novel blood biomarkers could be useful to improve patient management. The aim of the study was to evaluate the association of selected inflammation- and oxidative stress-related markers with the presence of severe stenosis and/or vulnerable plaques. METHODS: Circulating levels of soluble CD40 ligand, interleukin-10, macrophage inflammatory protein (MIP)-1α, endoglin, CD163, CD14, E-selectin, tumor necrosis factor-α, monocyte chemoattractant protein-1, C-Reactive protein, CD40 L + T lymphocytes, total antioxidant capacity, glutathione reductase activity, and protein carbonyl content were determined in patients with carotid atherosclerosis. RESULTS: Multiparametric analysis showed significantly higher levels of MIP-1α in patients with stenosis ≥70% than in patients with stenosis <70%, and significantly higher levels of CD14 in patients with hypoechoic (vulnerable) lesions compared to those with hyperechoic (stable) ones. The area under the curve obtained by the receiver operating characteristic curve analysis was 0.7253 for MIP-1α and 0.6908 for CD14. CONCLUSIONS: Our data suggest that circulating MIP-1α and CD14 levels are associated with the presence of advanced stenosis and of vulnerable carotid plaques.

Type 2 diabetes mellitus in obesity promotes prolongation of cardiomyocyte contractile function, impaired Ca2+ handling and protein carbonylation damage.

AIMS: To investigate whether the obesity associated to T2DM presented cardiomyocyte myocardial contractility dysfunction due to damage in Ca2+ handling, concomitantly with increased biomarkers of oxidative stress. METHODS: Male Wistar rats were randomized into two groups: control (C): fed with standard diet; and obese (Ob) that fed a saturated high-fat. After the characterization of obesity (12 weeks), the Ob animals were submitted to T2DM induction with a single dose of intraperitoneal (i.p.) injection of streptozotocin (30 mg/kg). Thus, remained Ob rats that were characterized as to the presence (T2DMOb; n = 8) and/or absence (Ob; n = 10) of T2DM. Cardiac remodeling was measured by post-mortem morphological, isolated cardiomyocyte contractile function, as well as by intracellular Ca2+-handling analysis. RESULTS: T2DMOb presented a significant reduction of all fat pads, total body fat and adiposity index. T2DMOb group presented a significant increase in protein carbonylation and superoxide dismutase (SOD) activity, respectively. T2DMOb promoted elevations in fractional shortening (15.6 %) and time to 50 % shortening (5.8 %), respectively. Time to 50 % Ca2+ decay was prolonged in T2DMOb, suggesting a possible impairment in Ca2+recapture and/or removal. CONCLUSION: Type 2 diabetes mellitus in obesity promotes prolongation of cardiomyocyte contractile function with protein carbonylation damage and impaired Ca2+ handling.

Prepubertal oral exposure to relevant doses of acrylamide impairs the testicular antioxidant system in adulthood, increasing protein carbonylation and lipid peroxidation.

The increased prevalence of human infertility due to male reproductive disorders has been linked to extensive exposure to chemical endocrine disruptors. Acrylamide (AA) is a compound formed spontaneously during the thermal processing of some foods that are mainly consumed by children and adolescents. We previously found that prepubertal exposure to AA causes reduced sperm production and functionality. Oxidative stress is recognized as the main cause of reduced sperm quality and quantity. In this sense, our objective was to evaluate the expression and activity of genes related to enzymatic antioxidant defense, nonprotein thiols, lipid peroxidation (LPO), protein carbonylation (PC) and DNA damage in the testes of rats exposed to acrylamide (2.5 or 5 mg/kg) from weaning to adult life by gavage. For the AA2.5 and AA5 groups, there were no alterations in the transcript expression of genes related to enzymatic antioxidant defense. The enzymatic activities and metabolic parameters were also not affected in the AA2.5 group. For the AA5 group, the enzymatic activities of G6PDH and GPX were reduced, SOD was increased, and protein carbonylation (PC) was increased. Data were also evaluated by Integrate Biomarker Response (IBRv2), a method to analyze and summarize the effects on biomarkers between doses. The IBRv2 index was calculated as 8.9 and 18.71 for AA2.5 and AA5, respectively. The following biomarkers were affected by AA2.5: decreased enzymatic activities of G6PDH, SOD, and GPX, increased GST and GSH, increased LPO and PC, and decreased DNA damage. For AA5, decreased enzymatic activities of G6PDH, GST, CAT and GPX, increased SOD and GSH, increased PC, and decreased LPO and DNA damage were observed. In conclusion, AA exposure during the prepubertal period causes imbalances in the testicular enzymatic antioxidant defense, contributing to the altered spermatic scenario in the testes of these rats.

Oxidative stress as regulator of neuronal impairment after exposure to hospital effluents in Danio rerio.

The variety of activities carried out within hospitals results in their final discharges being considered hotspots for the emission of emerging pollutants. Hospital effluents contain different substances capable of altering the health of ecosystems and biota, furthermore, little research has been done to elucidate the adverse effects of these anthropogenic matrices. Taking this into account, herein we aimed to establish whether exposure to different proportions (2 %, 2.5 %, 3 %, and 3.5 %) of hospital effluent treated by hospital wastewater treatment plant (HWWTP) can induce oxidative stress, behavioral alterations, neurotoxicity, and disruption of gene expression in Danio rerio brain. Our results demonstrate that the hospital effluent under-study induces an anxiety-like state and alters swimming behavior, as fish exhibited increased freezing episodes, erratic movements and traveled less distance than the control group. In addition, after exposure we observed a meaningful rise in biomarkers related to oxidative damage, such as protein carbonyl content (PCC), lipoperoxidation level (LPX), hydroperoxide content (HPC), as well as an increase in enzyme antioxidant activities of catalase (CAT), and superoxide dismutase (SOD) upon short-term exposure. Moreover, we discovered an inhibition of acetylcholinesterase (AChE) activity in a hospital effluent proportion-dependent manner. Regarding gene expression, a significant disruption of genes related to antioxidant response (cat, sod, nrf2), apoptosis (casp6, bax, casp9), and detoxification (cyp1a1) was observed. In conclusion, our outcomes suggest that hospital effluents enhance the emergence of oxidative molecules, and promote a highly oxidative environment at the neuronal level that favors the inhibition of AChE activity, which consequently explains the anxiety-like behavior observed in D. rerio adults. Lastly, our research sheds light on possible toxicodynamic mechanism by which these anthropogenic matrices may trigger damage in D. rerio brain.