Participation Of Oxidative Stress Research Articles

Participation of Oxidative Stress in the Activity of Compounds Isolated from Eleutherine plicata Herb.

From Eleutherine plicata, naphthoquinones, isoeleutherine, and eleutherol were isolated, and previous studies have reported the antioxidant activity of these metabolites. The present work evaluated the role of oxidative changes in mice infected with Plasmodium berghei and treated with E. plicata extract, fraction, and isolated compounds, as well as to verify possible oxidative changes induced by these treatments. E. plicata extracts were prepared from powder from the bulbs, which were submitted to maceration with ethanol, yielding the extract (EEEp), which was fractionated under reflux, and the dichloromethane fraction (FDMEp) was submitted for further fractionation, leading to the isolation of isoeleutherine, eleutherine, and eleutherol. The antimalarial activity was examined using the suppressive test, evaluating the following parameters of oxidative stress: trolox equivalent antioxidant capacity (TEAC), thiobarbituric acid reactive substances (TBARS), and reduced glutathione (GSH). Furthermore, the molecular docking of naphthoquinones, eleutherol, eleutherine, and isoeleutherine interactions with antioxidant defense enzymes was investigated, which was favorable for the formation of the receptor-ligand complex, according to the re-rank score values. Eleutherine and isoeleutherine are the ones with the lowest binding energy for catalase (CAT), glutathione reductase (GR), and glutathione peroxidase (GPx1), showing themselves as possible targets of these molecules in the involvement of redox balance. Data from the present study showed that treatments with E. plicata stimulated an increase in antioxidant capacity and a reduction in oxidative stress in mice infected with P. berghei, with naphthoquinones being responsible for reducing oxidative changes and disease severity.

Oxidative Stress Markers in Urine and Serum of Patients with Bladder Cancer.

Oxidative stress is defined as an imbalanced state of the production of reactive oxygen species and antioxidant capacity that causes oxidative damage to biomolecules, leading to cell injury and finally death. Oxidative stress mediates the development and progression of several cancer diseases, including bladder cancer. The aim of our study was to determine markers of levels of the oxidative stress in serum and urine in the same patients in parallel in serum and urine. Furthermore, we tried to estimate the associations between oxidative stress markers and the type of cancer, its clinical stage and grade, as the well as correlations between serum and urinary markers in patients with bladder cancer. Sixty-one bladder cancer and 50 healthy volunteers as a control group were included. We determined the serum and urine levels of advanced oxidation protein products (AOPP), Amadori products, total antioxidant capacity, total oxidant status (TOS), oxidative status index (OSI), and malondialdehyde. We confirm that almost all markers are elevated in serum and urine from patients with bladder cancer than from healthy subjects. Moreover, we did not find differences in the level of oxidative stress markers and the type of tumor, its clinical stage, and grade. We noted correlations between serum and urinary biomarkers, in particular TOS and OSI. Our results clearly indicate the participation of oxidative stress in the development of bladder cancer.

Cannabidiol attenuates hypersensitivity and oxidative stress after traumatic spinal cord injury in rats

Neuropathic pain (NP) arises as a direct consequence of traumatic spinal cord injury (SCI), which leads to devastating consequences for people suffering from this condition since no specific treatment has been defined. One relevant mechanism in generating painful stimuli involves the direct participation of reactive oxygen species (ROS) at the cellular and subcellular levels. Cannabidiol (CBD) is one of the two most crucial cannabinoid components of the cannabis plant and has been proposed as a potential treatment for NP. Its antioxidant, neuroprotective and anti-inflammatory properties have been documented. However, there is insufficient evidence regarding CBD as treatment of NP induced by SCI or the mechanisms that underlie this effect. In this study, we evaluated the antinociceptive effect of CBD as an acute treatment after the nociceptive behaviors characteristic of NP were established (hypersensitivity threshold and hypersensitivity response). Furthermore, the participation of oxidative stress was determined by lipid peroxidation (LP) and glutathione concentration (GSH) in female Wistar rats with SCI. Acute treatment with CBD (2.5–20 mg/kg, i.p.) decreased nociceptive behaviors in a dose-dependent manner, decreased LP, and increased GSH concentration in injured tissue 15 days after injury. The findings of this study suggest that the antinociceptive effect induced by CBD is regulated by reducing oxidative stress by decreasing the LP and increasing the concentration of antioxidant (GSH) defenses.

Oxidative stress activates Ryr2-Ca2+ and apoptosis to promote PM2.5-induced heart injury of hyperlipidemia mice

The increased cases of hyperlipemia in China and the crucial role of PM2.5 in inducing and promoting cardiovascular diseases have attracting more and more researchers’ attention. However, the effects and mechanisms of PM2.5 on cardiovascular system of hyperlipidemia people are still unclear. In this study, hyperlipidemia mice model was established by high-fat diet. Then we exposed these mice to PM2.5 or saline to explore the underling mechanism of cardiac injury in hyperlipidemia mice. The hyperlipemia mice are more susceptible to heart damage caused by PM2.5 exposure. The participation of oxidative stress, cell apoptosis and Ca2+ related mechanism could be observed in this model. After NAC (N-acetyl-L-cysteine) treatment, the oxidative stress level induced by PM2.5 exposure significantly decreased in hyperlipemia mice. NAC effectively alleviated cardiac injury, improved the imbalance of calcium and attenuated apoptosis induced by PM2.5 exposure in hyperlipemia mice. The strong oxidative stress in hyperlipemia mice could lead to calcium homeostasis imbalance and activation of apoptosis-related pathways. This mechanism of PM2.5-induced myocardial injury was also verified in vitro. In our present study, we demonstrated the contribution of the PM2.5-ROS-Ryr2-Ca2+ axis in PM2.5-induced heart injury of hyperlipidemia mice, offering a potential therapeutical target for related pathology.

ABSENCE OF OXIDATIVE STRESS AND SIRTUINS RECRUITMENT ON CARDIAC TISSUE POST STRESS

Stress has emerged as a factor associated with cardiovascular disease. Catecholamines released during the stress reaction by the sympathetic nerves and the adrenal medulla couple to β1-and β2-adrenoceptors in the cardiomyocytes membrane enhancing heart function in order to attend the organism demand. This might produce excessive reactive oxygen species what may culminate with oxidative stress and progression of several cardiac diseases. Sirtuins have been described as cardioprotective factors and important regulators of the cellular stress response in the heart. The aim of this work is to investigate the putative participation of oxidative stress and sirtuins in the heart of rats submitted to foot shock stress, an experimental model where there is up regulation of β2-adrenoceptors and downregulation of β1-adrenoceptors. The data have shown that in the myocardium of rats submitted to foot shock stress the H2O2 concentration, catalase and superoxide dismutase activity, NAD+/NADH ratio, as well as the protein expression of sirtuins 1 and 3 were not altered. Pharmacological blockade of the β2-adrenoceptors by ICI118,551, did not modify this scenario. It is concluded that foot shock stress does not cause disruptions in oxidative stress or redox state processes in the myocardium, and consequently, sirtuins are not recruited to stress response.

Gastroprotective action of the ethanol extract of Leonurus sibiricus L. (Lamiaceae) in mice

Ethnopharmacological relevanceLeonurus sibiricus L. (Lamiaceae) is a medicinal plant known in Brazil as “rubim” or “erva de macaé”. It is used for various purposes, including stomach disorders. Aim of the studyTo evaluate the effect of the ethanol extract of the aerial parts of L. sibiricus (EELs) in models of gastric damage in mice. Material and methodsThe effect of EELs (50, 100 and 300 mg/kg, p.o., 1 h before induction) was tested on acidified ethanol (ACEt)-induced gastric ulcers. Additionally, we tested the effect of EELs (by intraduodenal administration) in the pylorus ligation (PL) model. ResultsPretreatment with EELs, at 300 mg/kg, but not 50 and 100 mg/kg, reduced the relative area of gastric ulcers induced by ACEt (p < 0.01) and lipoperoxidation (p < 0.001), and increased the sulfhydryl content (p < 0.01) in the stomach in comparison with the vehicle group. Pretreatment with N-ethylmaleimide (a blocker of non-protein sulfhydryl groups, 10 mg/kg, i.p.) or glibenclamide (a KATP channel blocker, 10 mg/kg, i.p.) inhibited the gastroprotective response caused by EELs (300 mg/kg; p < 0.001), but there were no alterations due to pretreatments with inhibitors of the synthesis of prostaglandins (indomethacin, 10 mg/kg), nitric oxide (L-NAME, 70 mg/kg) or hydrogen sulfide (DL-propargylglycine, 10 mg/kg). Treatment with EELs (300 mg/kg) reduced mucus production (p < 0.001) and the volume of gastric secretion (p < 0.001) after PL without affecting gastric acidity or pH. ConclusionsThese results provide evidence that EELs exerts gastroprotective action in mice, with the participation of oxidative stress and mediation of NP-SH, KATP channels and mucus production.

Antiproliferative and antiangiogenic effects of ammonium tetrathiomolybdate in a model of endometriosis

AimsCopper (Cu) is involved in the endometriosis progression. Herein, an experimental endometriosis model was used to evaluate whether its chelation with ammonium tetrathiomolybdate (TM) affects the proliferation and angiogenesis in endometriotic-like lesions and the participation of oxidative stress in these processes. Main methodsFemale C57BL/6 mice were divided into three groups: sham-operated mice, endometriosis-induced mice, and TM-treated endometriosis-induced mice. Each animal in the third group received 0.3 mg of TM/day in their drinking water from the postoperative 15th day. The samples were collected after one month of induced pathology. In peritoneal fluids, Cu and estradiol levels were determined by electrothermal atomic absorption spectrometry and electrochemiluminescence, respectively. Endometriotic-like lesions were processed for the analysis of cell proliferation by PCNA immunohistochemistry, the expression of angiogenic markers by RT-qPCR, the presence of endothelial cells by immunofluorescent staining, and oxidative stress applying spectrophotometric methods. Key findingsTM treatment decreased Cu and estradiol levels, which were increased by this pathology. In lesions, TM induced: (a) a decrease in tissue weight and volume, (b) a decrease in PCNA-positive cells, (c) antiangiogenic effects by decreasing the number of blood vessels, the mRNA expression of fibroblast growth factor 2 (Fgf2) and platelet-derived growth factor subunit B (Pdgfb), and the presence of endothelial cells, (d) a decrease in antioxidant activity and an increase in lipid peroxidation. SignificanceTM is a highly effective antiproliferative and antiangiogenic agent, modulating oxidative imbalance in endometriosis. Its anti-endometriotic potential is an attractive feature of TM as a possible non-hormonal treatment.

Oxidative stress parameters as biomarkers of bladder cancer development and progression

The epidemiological studies confirm that the overproduction of free radical is an important factor of cancer induction as well as development, and loss of antioxidant systems efficiency is associated with an increased risk of carcinogenesis. While bladder cancer is the fourth most common type of cancer all over the world, there is little evidence of the advancing changes in oxidative/nitrative stress during the progression of bladder cancer. Our study aimed to investigate the plasma levels of typical markers of oxidative/nitrative stress depending on the clinical classification of bladder cancer differentiation and infiltration degree. We examined 40 patients with newly diagnosed bladder cancer and 20 healthy volunteers as a control group. We analysed the plasma levels of protein carbonyls, thiol groups, 3-nitrotyrosine, lipid peroxidation, as well as non-enzymatic plasma antioxidant capacity using DPPH· and ABTS·+ radicals. We confirmed that all analysed biomarkers are higher in enrolled BC patients than in healthy subjects. Furthermore, our findings demonstrate a positive correlation between the degree of bladder cancer progression and the level of oxidative stress, but no correlation in the case of NT-3. Based on obtained results, we might conclude that during carcinogenesis of the bladder increased oxidative damage of biomolecules is manifested. This indicates the participation of oxidative stress in the development of bladder cancer, and it is important the ensure the proper antioxidant protection.

Oxidative Stress and Vascular Damage in the Context of Obesity: The Hidden Guest.

The vascular system plays a central role in the transport of cells, oxygen and nutrients between different regions of the body, depending on the needs, as well as of metabolic waste products for their elimination. While the structure of different components of the vascular system varies, these structures, especially those of main arteries and arterioles, can be affected by the presence of different cardiovascular risk factors, including obesity. This vascular remodeling is mainly characterized by a thickening of the media layer as a consequence of changes in smooth muscle cells or excessive fibrosis accumulation. These vascular changes associated with obesity can trigger functional alterations, with endothelial dysfunction and vascular stiffness being especially common features of obese vessels. These changes can also lead to impaired tissue perfusion that may affect multiple tissues and organs. In this review, we focus on the role played by perivascular adipose tissue, the activation of the renin-angiotensin-aldosterone system and endoplasmic reticulum stress in the vascular dysfunction associated with obesity. In addition, the participation of oxidative stress in this vascular damage, which can be produced in the perivascular adipose tissue as well as in other components of the vascular wall, is updated.

Dapsone Prevents Allodynia and Hyperalgesia and Decreased Oxidative Stress After Spinal Cord Injury in Rats.

Prospective longitudinal experimental study. We evaluate the effect of dapsone on tactile allodynia and mechanical hyperalgesia and to determine its anti-oxidant effect in a spinal cord injury (SC) model in rats. Neuropathic pain (NP) as result of traumatic spinal cord injury is a deleterious medical condition with temporal or permanent time-course. Painful stimuli trigger a cascade of events that activate the N-methyl-D-aspartate (NMDA) receptor, inducing an increase in oxidative stress. Since there is no effective treatment for this condition, dapsone (4,4'diaminodiphenylsulfone) is proposed as potential treatment for NP. Its anti-oxidant, neuroprotective, and anti-inflammatory properties have been documented, however, there is no evidence regarding its use for treatment of NP induced by SCI. In this study, we evaluated the anti-allodynic and anti-hyperalgesic effect of dapsone as preventive or acute treatment after NP was already established. Furthermore, participation of oxidative stress was evaluated by measuring lipid peroxidation (LP) and glutathione concentration (GSH) in rats with SCI. Acute treatment with dapsone (3.1-25 mg/kg, i.p.) decreased nociceptive behaviors in a dose-dependent manner, decreased LP, and increased GSH in the injured tissue 15 days after the injury was produced. On the other hand, preventive treatment (3 h post-injury, once daily for 3 days) with dapsone (3.1-25 mg/kg, i.p.) yielded similar results. The findings suggest that the anti-nociceptive effect of dapsone is regulated through the decrease of oxidative stress and the excitotoxicity is associated with the activation of NMDA receptors.Level of Evidence: N/A.

THE EFFECTS OF HIGH SALT DIET AND EXERCISE ON THE WATER-SALT BALANCE AND BLOOD PRESSURE IN RATS

In the study which was prepared based on the factors that can take place in essential hypertension pathology; We aimed to investigate the interactions of intensive exercise, high salt and partial NOS inhibition applications with each other, the effects on water-salt balance and blood pressure, changes in the intrarenal dopaminergic system, which is an important natriuretic system, and the participation of oxidative stress. The rats were given intensive exercise on a treadmill at a speed of 25 m / min at 5% inclination for 30 minutes a day, LNNA at a concentration of 50 mg / L and a high salt diet of 4% for 7 days either separately or together. Blood pressures of the rats were measured on the first and last days of the experiment, and the rats were taken into metabolic cages; 24-hour water intake and urinevolume were measured. Dopamine levels were measured in 24-hour urine to detect intrarenal dopamine synthesis. In addition, oxidative stress parameters in the serums of rats; TAS, TOS and OSI levels were measured. Blood pressure was found to be high in the groups in which intensive exercise was applied together with LNNA and high salt diet. While there was no change in the water balance of this group, it was found that sodium excretion and dopamine levels increased in 24-hour urine. In addition, it was found that the total oxidant status increased in this group, and oxidative stress developed as a result of insufficient antioxidant system. It suggests that the reason of hypertension that develops with the application of intensive exercise together with LNNA and high salt diet may be due to the vascular resistance increasing effect of oxidative stress rather than water-salt retention and it points out the necessity of studies to fully detect vascular tissue oxidative stress markers and vascular oxidative damage.

Dexamethasone increased the survival rate in Plasmodium berghei-infected mice

The present study aimed to evaluate the effects of dexamethasone on the redox status, parasitemia evolution, and survival rate of Plasmodium berghei-infected mice. Two-hundred and twenty-five mice were infected with Plasmodium berghei and subjected to stimulation or inhibition of NO synthesis. The stimulation of NO synthesis was performed through the administration of L-arginine, while its inhibition was made by the administration of dexamethasone. Inducible NO synthase (iNOS) inhibition by dexamethasone promoted an increase in the survival rate of P. berghei-infected mice, and the data suggested the participation of oxidative stress in the brain as a result of plasmodial infection, as well as the inhibition of brain NO synthesis, which promoted the survival rate of almost 90% of the animals until the 15th day of infection, with possible direct interference of ischemia and reperfusion syndrome, as seen by increased levels of uric acid. Inhibition of brain iNOS by dexamethasone caused a decrease in parasitemia and increased the survival rate of infected animals, suggesting that NO synthesis may stimulate a series of compensatory redox effects that, if overstimulated, may be responsible for the onset of severe forms of malaria.

The Dependence between Urinary Levels of Angiogenesis Factors, 8-Iso-prostaglandin F2α, ɣ-Synuclein, and Interleukin-13 in Patients with Bladder Cancer: A Pilot Study.

During the last decade, a significant increase in the incidence of bladder cancer (BC) has been observed. Angiogenesis plays a key role in the process of tumor growth and metastasis. Additionally, the participation of oxidative stress and chronic inflammation in BC pathogenesis is indicated. The aim of the study was to evaluate the urinary levels of parameters of angiogenesis, stimulating angiogenin (ANG) and inhibiting angiostatin (ANGST), 8-iso-prostaglandin F2α (8-iso-PGF2α) as a marker of oxidative stress, ɣ-synuclein (SNCG) as a cancer progression parameter, and interleukin-13 (IL-13) as an anti-inflammatory immunomodulator. The levels of ANG, ANGST, 8-iso-PGF2α, SNCG, and IL-13 in the urine of BC patients and healthy controls were measured by the enzyme-linked immunosorbent assay. These parameters were examined in the whole group of BC patients and in subgroups depending on the clinical stage: nonmuscle-invasive bladder cancer (NMIBC) and muscle-invasive bladder cancer (MIBC); histopathologic malignancy: low grade (LG) and high grade (HG) and in primary and recurrent BC. Significantly, higher urinary parameters were found in BC patients in comparison to controls. Levels of all parameters increased with the development of cancer, with the exception of 8-iso-prostaglandin F2α, in which the level was higher in the early stages of the disease, but these differences were not statistically significant. Some correlations have been demonstrated between parameters in BC patients. Based on the receiver operating characteristic curves, ANG and ANGST had the best diagnostic value for BC. The obtained results indicate the important role of the examined parameters of angiogenesis, oxidative stress, and inflammation in the pathogenesis and development of BC. It is reasonable to continue research in order to thoroughly assess the impact of various associated processes on the course of BC. It is also important to carry out similar tests in patients with other urological diseases.

Postinfectious epilepsy (literature review)

Recently, a large amount of evidence has been obtained on the possible involvement of inflammatory processes in epileptogenesis. Thus, in a number of studies, an increase in the synthesis of specific inflammatory mediators in the brain of patients and, accordingly, the activation of some pro-inflammatory pathways in the foci of seizures, as well as the participation of oxidative stress, was found. There was also information that some chronic infections, such as neurocistercosis, HIV and herpes, without causing acute cerebral pathology, can provoke epileptic seizures and even the formation of refractory epilepsy in the future. This review summarizes the experimental and clinical data from studies on the relationship between epilepsy and chronic infectious diseases and neuroinflammation.

Patterns of cell death induced by metformin in human MCF-7 breast cancer cells

The ability to evade apoptosis is an important mechanism of drug resistance and tumor progression in breast cancer. The induction of different pathways of cell death could be an important strategy to limit tumor progression. Metformin, a drug used to treat type two diabetes, has demonstrated promising results in breast cancer experiments. However, little is known about the patterns of cell death induced by this drug. We analyzed the involvement of apoptosis, necroptosis and ferroptosis in the toxicity of metformin in MCF-7 cells, evaluating proliferation, viability and oxidative stress. It was used different inhibitors of cell death: Z-VAD, a pan-caspase inhibitor that blocks apoptosis; Necrostatin-1, which inhibits RIPK1 activity and blocks necroptosis; and the iron chelator, deferoxamine, that chelates iron and prevents ferroptosis. The participation of oxidative stress was analyzed through the evaluation of total thiols, reduced glutathione (GSH) and malondialdehyde (MDA). Our results showed that metformin increased cell death, reduced proliferation, thiol and GSH and increased MDA in cells. After the association between metformin and Z-VAD or Necrostatin-1, the drug toxicity was abolished. Ferroptosis did not significantly enrolled in metformin action against MCF-7 cells. The preservation of cellular antioxidants was found in all situations that cell death was blocked. Together, these results reveals that metformin induces necroptosis and apoptosis in MCF-7 cells and oxidative stress generation play a role in these two pathways of cell death. This information could help future studies to improve strategies to breast cancer treatment.

SRAGE and early signs of cardiac target organ damage in mild hypertensives

BackgroundSoluble Receptor for Advanced Glycation End Products (sRAGE) may be considered a marker inversely related to inflammation and its participation has been established in patients with advanced atherosclerotic vascular diseases. However, it is still unknown whether sRAGE reduction could be early metabolic change in the first stage of hypertension and initial hypertension-associated cardiac damage. We sought to determine the sRAGE values in otherwise healthy, untreated and recently diagnosed mild hypertensives and evaluate their association with blood pressure (BP) values, metabolic parameters, and with subclinical initial signs of cardiac target organ damage (TOD).MethodssRAGE were measured in 100 hypertensive and 100 normotensive subjects matched for age, gender and body mass index (BMI), submitted to a clinic visit and both ambulatory BP monitoring and echocardiography to determine the presence of initial cardiac TOD (presence of signs of left ventricular hypertrophy: left ventricular mass indexed for height2.7 (LVMi) > 48 g/m2.7 for men and > 44 g/m2.7 for women and/or increased left atrial volume 4-chamber indexed for body surface area (LAVi) > 34 ml/m2).ResultssRAGE levels were similar between hypertensive and normotensive subjects and were not significantly correlated with office and 24-h BPs values. However, when subgrouping the hypertensive patients in Hyp-TOD and Hyp-withoutTOD, sRAGE was found to be different among the three groups (p = 0.030), being lower in the Hyp-TOD group than the values of both Hyp-withoutTOD (p = 0.038) and normotensives (p = 0.038). In hypertensive patients sRAGE was negatively related with both LVMi (r = − 0.239, p = 0.034) and LAVi (r = − 0.315, p = 0.005) and was independently related to cardiac TOD also in multivariable analysis.ConclusionsIn this population of mild hypertensives, low circulating sRAGE may be a very early marker of initial TOD, suggesting the possible participation of oxidative stress in initial cardiac changes in human hypertension.

ATR/Chk1 Pathway is Activated by Oxidative Stress in Response to UVA Light in Human Xeroderma Pigmentosum Variant Cells.

The crucial role of DNA polymerase eta in protecting against sunlight-induced tumors is evidenced in Xeroderma Pigmentosum Variant (XP-V) patients, who carry mutations in this protein and present increased frequency of skin cancer. XP-V cellular phenotypes may be aggravated if proteins of DNA damage response (DDR) pathway are blocked, as widely demonstrated by experiments with UVC light and caffeine. However, little is known about the participation of DDR in XP-V cells exposed to UVA light, the wavelengths patients are mostly exposed. Here, we demonstrate the participation of ATR kinase in protecting XP-V cells after receiving low UVA doses using a specific inhibitor, with a remarkable increase in sensitivity and γH2AX signaling. Corroborating ATR participation in UVA-DDR, a significant increase in Chk1 protein phosphorylation, as well as S-phase cell cycle arrest, is also observed. Moreover, the participation of oxidative stress is supported by the antioxidant action of N-acetylcysteine (NAC), which significantly protects XP-V cells from UVA light, even in the presence of the ATR inhibitor. These findings indicate that the ATR/Chk1 pathway is activated to control UVA-induced oxidatively generated DNA damage and emphasizes the role of ATR kinase as a mediator of genomic stability in pol eta defective cells.

Isoflavin-β modifies muscle oxidative stress and prevents a thyrotoxicosis-induced loss of muscle mass in rats.

We sought to verify whether isoflavin-beta (Iso-β), a mixture of isoflavones with antioxidant properties, could prevent thyrotoxicosis-induced loss of muscle mass and the participation of oxidative stress (OS) in the mechanisms of this prevention. Two experimental periods of thyrotoxicosis induction were used in Wistar rats: 3 and 5 days to assess Iso-β effects before and after thyrotoxicosis-induced muscle wasting. After euthanasia, peritoneal fat and gastrocnemius muscle were collected, weighed, and muscle OS was assessed. Iso-β prevented the loss of gastrocnemius mass in thyrotoxic rats through the prevention of muscle OS generation during thyrotoxicosis, increasing muscle total antioxidant capacity and decreasing mitochondrial cytochrome c oxidase activity, lipid peroxidation, and protein carbonyl content. Iso-β decreased oxidative modification of proteins, which is known to exert a major role during proteolysis induction and is present in thyrotoxic myopathy, highlighting the potential action of Iso-β in this complication of the disease. Muscle Nerve 56: 975-981, 2017.

Cellular Response to Cu‐ and Zn‐Induced Oxidative Stress in Aspergillus fumigatus Isolated From Polluted Soils in Bulgaria

The fungal strain Aspergillus fumigatus 32 isolated from the tailings pond at the copper mine “Vlaykov vruh,” Bulgaria, showed high tolerance to Cu2+ and Zn2+. This study was designed to explore the relationship between Cu2+ and Zn2+ tolerance and cellular response to oxidative stress. The model strain was identified to species level by morphological and molecular methods. Fungal cultures were exposed to enhanced concentrations of metal ions. The effect of Cu2+ and Zn2+ was evaluated by the changes in fungal growth and morphology, the level of oxidative stress biomarkers, and the antioxidant activities of enzymes such as superoxide dismutase (SOD) and catalase (CAT). Two different cellular responses occurred: The concentrations of up to 500 μg/mL caused enhanced levels of oxidative stress biomarkers (glycogen and trehalose accumulation and oxidatively damaged protein content), as well as an increase in SOD and CAT activities. The treatment with concentrations from 500 to 2000 μg/mL led to enhanced glycogen consumption, accelerated proteolysis, and a decrease in SOD and CAT activities. The present results provide additional information about the participation of oxidative stress and antioxidant defense in enhanced tolerance of fungi isolated from metal‐polluted soils. Probably, survival at extremely high concentrations also requires the participation of other defense mechanisms. Furthermore, the enhanced understanding of these processes will provide essential tools for efficient remediation practices.

Mechanism of metformin action in MCF-7 and MDA-MB-231 human breast cancer cells involves oxidative stress generation, DNA damage, and transforming growth factor β1 induction.

The participation of oxidative stress in the mechanism of metformin action in breast cancer remains unclear. We investigated the effects of clinical (6 and 30μM) and experimental concentrations of metformin (1000 and 5000μM) in MCF-7 and in MDA-MB-231 cells, verifying cytotoxicity, oxidative stress, DNA damage, and intracellular pathways related to cell growth and survival after 24h of drug exposure. Clinical concentrations of metformin decreased metabolic activity of MCF-7 cells in the MTT assay, which showed increased oxidative stress and DNA damage, although cell death and impairment in the proliferative capacity were observed only at higher concentrations. The reduction in metabolic activity and proliferation in MDA-MB-231 cells was present only at experimental concentrations after 24h of drug exposition. Oxidative stress and DNA damage were induced in this cell line at experimental concentrations. The drug decreased cytoplasmic extracellular signal-regulated kinases 1 and 2 (ERK1/2) and AKT and increased nuclear p53 and cytoplasmic transforming growth factor β1 (TGF-β1) in both cell lines. These findings suggest that metformin reduces cell survival by increasing reactive oxygen species, which induce DNA damage and apoptosis. A relationship between the increase in TGF-β1 and p53 levels and the decrease in ERK1/2 and AKT was also observed. These findings suggest the mechanism of action of metformin in both breast cancer cell lineages, whereas cell line specific undergoes redox changes in the cells in which proliferation and survival signaling are modified. Taken together, these results highlight the potential clinical utility of metformin as an adjuvant during the treatment of luminal and triple-negative breast cancer.