Appearance Of Oxidative Stress Research Articles

Characterization of novel marine bacteria isolated from deep Atlantic Ocean in Morocco as a source of natural bioactive compounds to control infections in aquaculture

With the rapid expansion of aquaculture production, there has been a concomitant increase in fish diseases, generally combatted by the utilization of chemicals and antibiotics. However, their overuse leads to the emergence of drug-resistant microorganisms and the appearance of oxidative stress. Consequently, antibiotics contribute to a reduction in fish immune defense. In this work, eight marine bacteria were characterized using physiological, biochemical and microbiological tests, and were evaluated for their safety by studying their haemolytic and gelatinase activities. Then, we evaluated their ability to produce active biomolecules and tested their in vitro antibacterial activities against five bacterial pathogens that are highly prevalent in aquaculture. Moreover, we evaluated their antioxidant potential using DPPH, ABTS and ferric reducing power tests. The obtained results revealed that cell-free supernatants were effective, they exhibited good antioxidant and antibacterial activities. Their biomolecules showed good stability under different temperatures ranging from 60 to 121 °C and were found to be chemically composed of peptides, exopolysaccharides and polyphenols. Therefore, the secreted bioactive substances are of great biotechnological interest and constitute a promising eco-friendly alternative to antibiotics and chemical agents in the context of sustainable aquaculture.

The mechanisms of microcystin-LR-induced genotoxicity and neurotoxicity in fish and mammals: Bibliometric analysis and meta-analysis

Microcystin-leucine arginine (MC-LR) is a typical cyanobacterial toxin, and the threat of this toxin is increasing among organisms. Despite extensive toxicological studies on MC-LR, there is no comprehensive analysis based on previously published data. Therefore, we conducted bibliometric analysis and meta-analysis to identify research hotspots and to elucidate the key mechanism of the relationship between MC-LR and genotoxicity and neurotoxicity among fish and mammals. One of the hotspots is toxic mechanisms (indicated by the frequent appearance of oxidative stress, DNA damage, apoptosis, neurotoxicity, genotoxicity, ROS, comet assay, signalling pathway, and gene expression indicate as keywords). The density visualization shows a high frequency of “microcystin-LR” and “toxicology,” and the overlay visualization emphasizes the prominence of “neurotoxicity” in recent years. These findings confirm the importance of studying MC-LR toxicity. Meta-analysis indicated that in both fish and mammals, MC-LR exposure increased ROS levels by 294 % and increased DNA damage biomarkers by 174 % but decreased neurotoxicity biomarkers by 9 %. Intergroup comparisons revealed that the exposure concentration of MC-LR was significantly correlated with genotoxicity and neurotoxicity levels in both fish and mammals (p < 0.05). Furthermore, the random forest (RF) model revealed that exposure concentration was the primary determinant associated with the induction of ROS, genotoxicity, and neurotoxicity induced by MC-LR. This is likely the dominant mechanism by which excessive ROS production induced by MC-LR causes oxidative stress, ultimately leading to genotoxicity and neurotoxicity in both fish and mammals.

SnRK2.10 kinase differentially modulates expression of hub WRKY transcription factors genes under salinity and oxidative stress in Arabidopsis thaliana.

In nature, all living organisms must continuously sense their surroundings and react to the occurring changes. In the cell, the information about these changes is transmitted to all cellular compartments, including the nucleus, by multiple phosphorylation cascades. Sucrose Non-Fermenting 1 Related Protein Kinases (SnRK2s) are plant-specific enzymes widely distributed across the plant kingdom and key players controlling abscisic acid (ABA)-dependent and ABA-independent signaling pathways in the plant response to osmotic stress and salinity. The main deleterious effects of salinity comprise water deficiency stress, disturbances in ion balance, and the accompanying appearance of oxidative stress. The reactive oxygen species (ROS) generated at the early stages of salt stress are involved in triggering intracellular signaling required for the fast stress response and modulation of gene expression. Here we established in Arabidopsis thaliana that salt stress or induction of ROS accumulation by treatment of plants with H2O2 or methyl viologen (MV) induces the expression of several genes encoding transcription factors (TFs) from the WRKY DNA-Binding Protein (WRKY) family. Their induction by salinity was dependent on SnRK2.10, an ABA non-activated kinase, as it was strongly reduced in snrk2.10 mutants. The effect of ROS was clearly dependent on their source. Following the H2O2 treatment, SnRK2.10 was activated in wild-type (wt) plants and the induction of the WRKY TFs expression was only moderate and was enhanced in snrk2.10 lines. In contrast, MV did not activate SnRK2.10 and the WRKY induction was very strong and was similar in wt and snrk2.10 plants. A bioinformatic analysis indicated that the WRKY33, WRKY40, WRKY46, and WRKY75 transcription factors have a similar target range comprising numerous stress-responsive protein kinases. Our results indicate that the stress-related functioning of SnRK2.10 is fine-tuned by the source and intracellular distribution of ROS and the co-occurrence of other stress factors.

Characterization of cellular toxicity induced by sub-lethal inorganic mercury in the marine microalgae Chlorococcum dorsiventrale isolated from a metal-polluted coastal site

Mercury (Hg) is a global pollutant that affects numerous marine aquatic ecosystems. We isolated Chlorococcum dorsiventrale Ch-UB5 microalga from coastal areas of Tunisia suffering from metal pollution and analyzed its tolerance to Hg. This strain accumulated substantial amounts of Hg and was able to remove up to 95% of added metal after 24 and 72 h in axenic cultures. Mercury led to lesser biomass growth, higher cell aggregation, significant inhibition of photochemical activity, and appearance of oxidative stress and altered redox enzymatic activities, with proliferation of starch granules and neutral lipids vesicles. Such changes matched the biomolecular profile observed using Fourier Transformed Infrared spectroscopy, with remarkable spectral changes corresponding to lipids, proteins and carbohydrates. C. dorsiventrale accumulated the chloroplastic heat shock protein HSP70B and the autophagy-related ATG8 protein, probably to counteract the toxic effects of Hg. However, long-term treatments (72 h) usually resulted in poorer physiological and metabolic responses, associated with acute stress. C. dorsiventrale has potential use for Hg phycoremediation in marine ecosystems, with the ability to accumulating energetic reserves that could be used for biofuel production, supporting the notion of using of C. dorsiventrale for sustainable green chemistry in parallel to metal removal.

Impact of Acute Blood Loss on Clinical, Hematological, Biochemical, and Oxidative Stress Variables in Sheep.

Blood loss in sheep can have different causes and may result in anemia. We aimed to evaluate the clinical, hematological, and biochemical alterations and the oxidative stress generated by acute blood loss. Eighteen healthy sheep underwent phlebotomy to remove 40% of the blood volume and were evaluated clinically and by laboratory tests for clinical, biochemical, and blood gas variables and to assess oxidative stress before induction (T0), 30 min (T30 min), and 6 (T6 h), 12 (T12 h), and 24 h (T24 h) after blood loss. The sheep showed tachycardia from T30 min until T24 h, reduction in the hematocrit, number of erythrocytes, and hemoglobin concentration, with lower values at T24 h and increase in the number of leukocytes from T12 h on. There was a reduction in blood pH and oxygen pressure at T30 min, increased lactate concentration and reduced blood bicarbonate at this time. There was an increase in urea concentration from T6 h until the end of the study, with no change in creatinine levels. The animals did not show changes in the concentration of malonaldehyde, and in the activity of the enzymes superoxide dismutase, glutathione peroxidase, and catalase, but there was a reduction in the concentration of reduced glutathione at T24 h. The acute loss of 40% of blood volume is capable of promoting relevant clinical, hematological, blood gas, and biochemical alterations, and contributed to the appearance of oxidative stress with reduced glutathione concentration, suggesting that this process generated free radicals in sufficient quantity to diminish the action of antioxidants.

Oxidative Stress Markers in COPD Patients Admitted to Pulmonary Rehabilitation

Background: Chronic obstructive pulmonary disease (COPD) is a pathology, which leads to an irreversible and progressive reduction of the airflow, usually caused by smoking, but only present in 25% of smokers. Some mechanisms involved in the onset and progression of the disease are local and systemic factors such as inflammation, exacerbated immune response and the appearance of oxidative stress. For all these reasons, the use of oxidative stress parameters as progression markers or even as a way to monitor the response of any kind of non-pharmacological interventions, like the use of pulmonary rehabilitation (PR), is feasible. Aims: The study aims to determine markers of oxidative stress levels in plasma and erythrocytes in patients with COPD through the application of a PR protocol. Methods: The study included 25 patients diagnosed with COPD according to the GOLD criteria with a medical indication of PR and attendance at the gym in San José Hospital, Santiago, Chile. Blood samples were obtained before the start of the protocol, in the 10th session, and at the end of the protocol (20th session). These samples were stored for oxidative stress determinations: FRAP (ferric reducing ability of plasma), F2-isoprostanes, reduced (GSH)/oxidized (GSSG) ratio and antioxidant enzyme activity in the erythrocyte. In all stages, associations between events and clinical parameters in patients have been observed. The clinical parameters assessed were the six-minute walking test (6MWT), maximal inspiratory and expiratory pressure, the BODE index and Saint George’s respiratory questionnaire, which includes quality of life. Results: The intracellular and extracellular capacity (GSH/GSSG and FRAP) in patients in PR at the 10th session were 53.1 and 34% higher than basal values, respectively. Only the GSH/GSSG ratio was 38.2% lower at the 20th session, related in part with higher plasma and erythrocyte lipid peroxidation at baseline. This could be due to the high concentration of reactive oxygen species in the first sessions, which has been reported in the literature as the acute effect of controlled exercise. Blood lipid peroxidation was 43.34 and 58.34% lower at the 10th and 20th sessions, respectively, demonstrating the improvements in the oxidative parameters with long-term exercise. With respect to oxidative enzyme activity, superoxide dismutase and catalase showed higher values of activity at the 10th and 20th sessions compared to the baseline. In the clinical parameters of the PR, significant changes were found in the BODE index and Saint George’s questionnaire, with these results being associated with a less predictive mortality score and a better understanding of the disease. This may be because the patients achieved longer distances in the 6MWT and better understood the disease at the end of the PR. Conclusion: The goal of this study was to contribute to the pathophysiological basis for further research on COPD patients, a disease of high prevalence in Chile. This study could support the basis for non-pharmacological strategies such a PR.

Study of the dynamics of catalase activity in heart and muscle of rats by mechanical action on the barrier gematologichesky

The hematoophthalmic barrier is one of the mechanisms of resistance that serves to protect the body and prevents homeostasis disorder when the body is affected by factors that can disturb this balance. One of the complications of mechanical trauma of the eye and violation of the hematoophthalmic barrier is the appearance of oxidative stress on the background of the general inflammatory process in violation of cellular structures. Objective: to study the dynamics of catalase activity in the heart and muscle tissue of rats under oxidative stress caused by mechanical action on the hematoophthalmic barrier. Materials and methods. The study was carried out on white neonatal mature healthy male rats of six months of age, weighing 200–220 g and having 150 pieces. The activity of catalase in heart and muscle tissue was studied before the beginning of the experiment, as well as on the 1st, 3rd, 5th, 7th and 14th day of the experiment using the standard Korolyuk M.A. method. The dynamics of catalase activity was evaluated by different methods of treatment of mechanical eye trauma, including the use of quercetin antioxidant. The results of the study. It was found that in addition to the standard therapy of mechanical eye injury injection of quercetin, the activity of catalase in the heart and muscular tissue after falling on the background of induced oxidative stress increases to the values of physiological norm by 14 days, which indicates the effective elimination of oxidative stress. Conclusions. The activity of catalase in rat heart and muscle tissue under oxidative stress caused by mechanical influence on hematoophthalmic barrier is most effectively stabilized under standard therapy of mechanical eye injury with addition of quercetin in the form of injections.

Antioxidant properties of hidazepam and amitriptyline with pain syndrome of rats

Peroxide modification of cell biostructures and functions due to the activation of free radical oxidative processes underlies the pathogenesis of a significant number of diseases different in its etiology. The ability of pharmacological drugs which have antioxidant properties inhibit free radical peroxide oxidation and stabilize the structure and function of cell membranes and thus create optimal conditions for the preservation of homeostasis of cells and tissues. It makes pathogenetically grounded their widespread using in medical practice. Therefore, it was expedient to study the effect on the state of lipid peroxidation in the case of the development of the pain syndrome of drugs which are used during anesthesia as an adjuvant.&#x0D; For the study, drugs from the group of psychotropic drugs were selected as adjuvants. This is due to that pain syndromes of the different origin often cause psycho-emotional disorders. In addition, pain is not only a symptom of many acute and chronic diseases but also a complex psycho-physiological phenomenon which involves the mechanisms of the regulation and the formation of emotions and motor, humoral and hemodynamic reactions.&#x0D; The use of antidepressants in combination with other analgesics pharmaceuticals proved to be effective in placebo-controlled trials in the patients with the chronic pain syndrome. Among the drugs from the group of tranquilizers the greatest application in our time have been acquired derivatives of benzodiazepine. They are recommended for use on the background of analgesics in the case of the treatment of chronic pain syndrome in order to reduce effects of the excitement, anxiety, muscle tension, as effective and safe sleeping pills.&#x0D; So the purpose of the work is to study the effects of hidasepam and amitriptyline with the prophylactic and therapeutic administration on the intensity of the processes of the lipid peroxidation in serum, erythrocyte membranes, homogenate of rat spinal cord in case of the development of pain syndrome.&#x0D; The results of the research indicate that the development of pain syndrome caused by subcutaneous administration in the dorsal surface of the foot of the right posterior paw of the animal 0,1 ml 2% aqueous solution of formalin is accompanied by the appearance of oxidative stress in the experimental animals. In blood serum, erythrocyte membranes, spinal cord homogenates, the content of TBC-active products of the lipid peroxidation increases. Prophylactic-therapeutic administration of hidazepam per os in a dose 0,02 mg/kg of the body weight of animals prevents the development of oxidative stress in the investigated biological substances thus protecting them from damage and reducing the intensity of the pathological process. Pprophylactic and therapeutic administration of amitriptyline per os in a dose 16 mg/kg of the animals weight does not affect the intensity of the lipid peroxidation processes. The obtained results allow to optimize the treatment regimens due to the combined using of the non-narcotic analgesics and the non-steroidal anti-inflammatory drugs with the adjuvant anti-oxidant drugs from the group of the psychotropic medicines.

Study of Some Parameters of Recovered Sperm from Vitamin Ctreated Endometriotic Rats Model

The present study was designed to reveal the biochemical and parameters changes of the retrieval sperms uteri of surgically-induced endometriotic rats post 30 min and 1h of coupling. Seventy-five adult female rats were divided into 3 groups as follows: Group 1: 25 shame-operated female rats were orally administrated with 0.1 ml of d.w for 35 days. Group 2: 25 endometriotic female rats were orally administrated with 0.1 ml of d.w for 35 days. Groups 3: 25 endometriotic female rats were orally administrated with 200 mg/Kg of vitamin C for 35 days. At the end of administration, 10 female rats of each groups were mated with fertile males to study sperm parameters. Whereas, others 15 endometriotic female rats were left without mating to use their uteri for leukocytes counts, oxidative markers and PGF2α assay. The retrieval sperms from uteri of endometriotic rats (G2) were showed a significant (p≤0.05) lower in their functions parameters "concentration, viability, progressive motility, and the activity of LDH-C4 enzyme depending on the remaining them in the uteri compared to those values of retrieval sperms from control (G1) and unmated endometriotic rats that treated with vitamin C (G3). Also, the uterine flushing fluids of endometriotic rats (G2) exhibited that had a significant (p≤0.01) increase in the levels of leukocyte counts compared to those values of control (G1) and unmated endometriotic rats with vitamin C (G3). Whereas, there was no significant (P&gt;0.05) difference in the levels of PGF2α in the uterine tissue of all unmated endometriotic groups (G1, G2 and G3). Surgically-induced endometriotic passive influence affected uterine milieu via an appearance of oxidative stress that increased significantly (p≤0.01) as a result of leukocytes count elevation. Ditto, there passive variables in the uterine microenvironment was reflected on the sperm functions parameters leading to infertility. While, the role of vitamin C in ameliorate of all above passive variants was evident.

Edaravone presents antidepressant-like activity in corticosterone model of depression in mice with possible role of Fkbp5, Comt, Adora1 and Slc6a15 genes

Chronic exposure to environmental-like stress leads to dysregulation of hypothalamic–pituitary–adrenal (HPA) axis and to appearance of oxidative stress, which is implicated in the development of depression-like behaviour. Edaravone (3-methyl-1-phenyl-2-pyrazoline-5-one) exhibits a neuroprotective effect attributed to the potent free radical scavenging. This study was designed to assess antidepressant-like activity of edaravone based on behavioural tests in the animal model of depression. Furthermore, to elucidate its mechanisms, the expression of Fkbp5, Comt, Adora and Slc6a15 genes involved in turnover of neurotransmitters was analysed. In order to evaluate the antioxidant features of edaravone, DNA's oxidative damage was determined. The mice were injected subcutaneously (sc) with 40 mg/kg corticosterone, chronically for 21 days. Paroxetine (10 mg/kg) (a selective serotonin reuptake inhibitor) and edaravone (10 mg/kg) were administered separately (ip) 30 min prior to the corticosterone injection. After 21-days of treatment with respective drugs, the mice were decapitated and the prefrontal cortex was rapidly dissected and used for determination of DNA's oxidative damage and the real-time PCR analysis. Edaravone ameliorated behavioural impairments in sucrose preference test (SPT) and forced swim test (FST). A possible role in Fkbp5, Comt, Adora1 and Slc6a15 genes' expression in mediating this effect is postulated. Both edaravone and paroxetine have no effect on corticosterone-induced DNA's oxidative damage.

Dermal exposure to nano-TiO2 induced cardiovascular toxicity through oxidative stress, inflammation and apoptosis.

Due to its excellent properties such as ultraviolet obscuration, chemical stability and small particle size, nano-titanium dioxide (nano-TiO2) is widely used, particularly in sunblock products. The skin is therefore a chief route for exposure. Studies have found that oral or respiratory exposure to nano-TiO2 has an adverse impact on the cardiovascular system. The relationship between dermal exposure to nano-TiO2 and cardiovascular system toxicity, particularly the causative mechanisms, remain unclear. In this study, we used Balb/c mice to evaluate cardiovascular toxicity from nano-TiO2 dermal exposure, and the underlying mechanisms associated with the human umbilical vein endothelial cells (HUVECs) were explored. Our results showed that nano-TiO2 treatment resulted in an obvious increase in reactive oxygen species and 8-hydroxy-2'-deoxyguanosine, indicating the appearance of oxidative stress. Moreover, the levels of inflammatory biomarkers, such as immunoglobulin E, soluble intercellular adhesion molecule-1, interleukin-8, and hypersensitive C-reactive protein, also increased. Exposing HUVECs to nano-TiO2 led to a decline in cell vitality, and an increase in caspase-3 levels, suggesting that nano-TiO2 exposure caused cytotoxicity and even cell apoptosis. Interestingly, neutralizing oxidative stress by administering Vitamin E was shown to reduce the inflammatory response and cytotoxicity. Our findings suggest that nano-TiO2 can injure the cardiovascular system via dermal exposure, and does this via oxidative stress-induced inflammation and cytotoxicity. Vitamin E treatment may be a strategy to mitigate the damage.

CORRECTION OF PROCESSES OF LIPID PEROXIDATION AND ENDOGENIC TOXICITY WITH EXTRACT OF GERANIUM PALUSTRE HERB AS A DENTAL FILM IN CONDITIONS OF EXPERIMENTAL STOMATITIS

The development of stomatitis is characterized by the appearance of oxidative stress, which is marked by an increase in the intensity of peroxide lipid oxidation processes, resulting in metabolic disturbance in oral mucosa. As a result, toxic substances accumulate and endogenic toxicity develops. Thus, correction of pathological processes in the oral mucosa with antioxidant medication enables to optimize the intensity of inflammation, shorten the period of catabolic phase and accelerate the regeneration. Extract of Geranium palustre herb as a dental film was used to reduce the intensity of processes of lipid peroxidation and endogenous intoxication. This treatment method enables to release an active substance from the drug locally and to provide optimal therapeutic effect. The efficacy of the experimental medication was studied in the dynamics of experimental ulcerative stomatitis development in rabbits. The experimental model of ulcerative stomatitis in animals was induced with a burn method. For the experiment, the animals were divided into 2 groups: control group, where treatment was not performed, and experimental group, where animals were treated by applying a dental film with Geranium palustre extract. The monitoring was conducted on the 3rd, 5th, 7th and 10th days of the experiment, which are key stages of healing.&#x0D; During these periods, blood was taken under anesthesia from the auricular vein of each experimental animal. Dynamics of prooxidant processes was detected by the level of lipid hydroperoxides and malondialdehyde, and the level of endogenic toxicity by the content of middle molecules. Statistic processing of the obtained results of investigation was performed using personal computer with installed proper software package StatSoft Statistica 10. Reliable difference was considered р&lt;0.05.&#x0D; It has been shown that extract of Geranium palustre herb, as a dental film, has antioxidant properties, which are effectively reducing the intensity of lipid peroxidation processes. It should be mentioned that the content of lipid hydroperoxides and final product of lipid peroxidation processes – malondialdehyde – in experimental animals’ blood was statistically lower in all periods of investigation than in control group, where treatment was not performed. The obtained results show that higher inhibiting effect of experimental medication is marked during the final stage of lipid peroxide oxidation than during the initial stage.&#x0D; As the result showed, the development of endogenic toxicity was observed in both groups and the highest indices were recorded at the peak of the inflammatory process on the third day of the experiment. Dynamics of middle molecules content shows that application of Geranium palustre extract, as a dental film, decreases this index during all investigated periods and reduces intoxication level in experimental animals.&#x0D; Thus, application of dental film in stomatitis treatment enables to release medication directly into the damaged area, which significantly increases therapeutic effect of biologically active substances of Geranium palustre phytocomplex, and rapid absorption of the film in the oral cavity provides easy use. Considering efficacy, non-toxicity and availability of the investigated medication, the expediency of its application in dental practice for the treatment of stomatitis and other inflammatory diseases of the oral mucosa may be considered.

Metal-induced oxidative stress in terrestrial macrolichens

Short-term (24 h) responses of Cladonia arbuscula subsp. mitis and Cladonia furcata to copper (CuII) or chromium (CrIII) excess (10 or 100 μM) were compared. C. arbuscula accumulated more Cu and Cr at higher metal doses but both species revealed depletion of K and/or Ca amount. Not only Cu but also Cr typically elevated reactive oxygen species (ROS) formation (fluorescence microscopy detection of total ROS and hydrogen peroxide) and depleted nitric oxide (NO) signal, with Cu showing more negative impact on lipid peroxidation (BODIPY 581/591 C11 staining reagent). Metals and staining reagents also affected anatomical responses and photobiont/mycobiont visibility. Principally different impact of Cu and Cr was observed at antioxidative metabolites level, indicating various ways of metal-induced ROS removal and/or metal chelation: Cu strongly depleted glutathione (GSH) and stimulated phytochelatin 2 (PC2) content while ascorbic acid accumulation was depleted by Cu and stimulated by Cr. Subsequent experiment with GSH biosynthetic inhibitor (buthionine sulfoximine, BSO) revealed that 48 h of exposure is needed to deplete GSH and BSO-induced depletion of GSH and PC2 amounts under Cu or Cr excess elevated ROS but depleted NO. These data suggest close relations between thiols, NO and appearance of oxidative stress (ROS generation) under metallic stress also in lichens.

Involvement of Astrocytes in Alzheimer’s Disease from a Neuroinflammatory and Oxidative Stress Perspective

Alzheimer disease (AD) is a frequent and devastating neurodegenerative disease in humans, but still no curative treatment has been developed. Although many explicative theories have been proposed, precise pathophysiological mechanisms are unknown. Due to the importance of astrocytes in brain homeostasis they have become interesting targets for the study of AD. Changes in astrocyte function have been observed in brains from individuals with AD, as well as in AD in vitro and in vivo animal models. The presence of amyloid beta (Aβ) has been shown to disrupt gliotransmission, neurotransmitter uptake, and alter calcium signaling in astrocytes. Furthermore, astrocytes express apolipoprotein E and are involved in the production, degradation and removal of Aβ. As well, changes in astrocytes that precede other pathological characteristics observed in AD, point to an early contribution of astroglia in this disease. Astrocytes participate in the inflammatory/immune responses of the central nervous system. The presence of Aβ activates different cell receptors and intracellular signaling pathways, mainly the advanced glycation end products receptor/nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway, responsible for the transcription of pro-inflammatory cytokines and chemokines in astrocytes. The release of these pro-inflammatory agents may induce cellular damage or even stimulate the production of Aβ in astrocytes. Additionally, Aβ induces the appearance of oxidative stress (OS) and production of reactive oxygen species and reactive nitrogen species in astrocytes, affecting among others, intracellular calcium levels, NADPH oxidase (NOX), NF-κB signaling, glutamate uptake (increasing the risk of excitotoxicity) and mitochondrial function. Excessive neuroinflammation and OS are observed in AD, and astrocytes seem to be involved in both. The Aβ/NF-κB interaction in astrocytes may play a central role in these inflammatory and OS changes present in AD. In this paper, we also discuss therapeutic measures highlighting the importance of astrocytes in AD pathology. Several new therapeutic approaches involving phenols (curcumin), phytoestrogens (genistein), neuroesteroids and other natural phytochemicals have been explored in astrocytes, obtaining some promising results regarding cognitive improvements and attenuation of neuroinflammation. Novel strategies comprising astrocytes and aimed to reduce OS in AD have also been proposed. These include estrogen receptor agonists (pelargonidin), Bambusae concretio Salicea, Monascin, and various antioxidatives such as resveratrol, tocotrienol, anthocyanins, and epicatechin, showing beneficial effects in AD models.

TXNIP/TRX/NF-κB and MAPK/NF-κB pathways involved in the cardiotoxicity induced by Venenum Bufonis in rats.

Venenum Bufonis (VB) is a widely used traditional medicine with serious cardiotoxic effects. The inflammatory response has been studied to clarify the mechanism of the cardiotoxicity induced by VB for the first time. In the present study, Sprague Dawley (SD) rats, were administered VB (100, 200, and 400 mg/kg) intragastrically, experienced disturbed ECGs (lowered heart rate and elevated ST-segment), increased levels of serum indicators (creatine kinase (CK), creatine kinase isoenzyme-MB (CK-MB), alanine aminotransferase (ALT), aspartate aminotransferase (AST)) and serum interleukin (IL-6, IL-1β, TNF-α) at 2 h, 4 h, 6 h, 8 h, 24 h, and 48 h, which reflected that an inflammatory response, together with cardiotoxicity, were involved in VB-treated rats. In addition, the elevated serum level of MDA and the down-regulated SOD, CAT, GSH, and GPx levels indicated the appearance of oxidative stress in the VB-treated group. Furthermore, based on the enhanced expression levels of TXNIP, p-NF-κBp65, p-IκBα, p-IKKα, p-IKKβ, p-ERK, p-JNK, and p-P38 and the obvious myocardial degeneration, it is proposed that VB-induced cardiotoxicity may promote an inflammatory response through the TXNIP/TRX/NF-κB and MAPK/NF-κB pathways. The observed inflammatory mechanism induced by VB may provide a theoretical reference for the toxic effects and clinical application of VB.

Oxidative Stress in Diabetic Nephropathy with Early Chronic Kidney Disease.

The increase in the prevalence of diabetes mellitus (DM) and the secondary kidney damage produces diabetic nephropathy (DN). Early nephropathy is defined as the presence of microalbuminuria (30–300 mg/day), including normal glomerular filtration rate (GFR) or a mildly decreased GFR (60–89 mL/min/1.73 m2), with or without overt nephropathy. The earliest change caused by DN is hyperfiltration with proteinuria. The acceptable excretion rate of albumin in urine is <30 mg/day. Albuminuria represents the excretion of >300 mg/day. Chronic kidney disease (CKD) is characterized by abnormalities in renal function that persist for >3 months with health implications. Alterations in the redox state in DN are caused by the persistent state of hyperglycemia and the increase in advanced glycation end products (AGEs) with ability to affect the renin-angiotensin system and the transforming growth factor-beta (TGF-β), producing chronic inflammation and glomerular and tubular hypertrophy and favoring the appearance of oxidative stress. In DN imbalance between prooxidant/antioxidant processes exists with an increase in reactive oxygen species (ROS). The overproduction of ROS diminishes expression of the antioxidant enzymes (manganese superoxide dismutase, glutathione peroxidase, and catalase). The early detection of CKD secondary to DN and the timely identification of patients would permit decreasing its impact on health.

Measuring In Vivo Free Radical Production by the Outer Retina.

Excessive and continuously produced free radicals in the outer retina are implicated in retinal aging and the pathogenesis of sight-threatening retinopathies, yet measuring outer retinal oxidative stress in vivo remains a challenge. Here, we test the hypothesis that continuously produced paramagnetic free radicals from the outer retina can be measured in vivo using high-resolution (22-μm axial resolution) 1/T1magnetic resonance imaging (MRI) without and with a confirmatory quench (quench-assisted MRI). Low-dose sodium iodate-treated and diabetic C57Bl6/J mice (and their controls), and rod-dominated (129S6) or cone-only R91W;Nrl-/- mice were studied. In dark-adapted groups, 1/T1 was mapped transretinally in vivo without or with (1) the antioxidant combination of methylene blue (MB) and α-lipoic acid (LPA), or (2) light exposure; in subgroups, retinal superoxide production was measured ex vivo (lucigenin). In the sodium iodate model, retinal superoxide production and outer retina-specific 1/T1 values were both significantly greater than normal and corrected to baseline with MB+LPA therapy. Nondiabetic mice at two ages and 1.2-month diabetic mice (before the appearance of oxidative stress) had similar transretinal 1/T1 profiles. By 2.3 months of diabetes, only outer retinal 1/T1 values were significantly greater than normal and were corrected to baseline with MB+LPA therapy. In mice with healthy photoreceptors, a light quench caused 1/T1 of rods, but not cones, to significantly decrease from their values in the dark. Quench-assisted MRI is a feasible method for noninvasively measuring normal and pathologic production of free radicals in photoreceptors/RPE in vivo.

Nitric oxide donor modulates cadmium-induced physiological and metabolic changes in the green alga Coccomyxa subellipsoidea

The impact of two concentrations (10 and 100μM) of cadmium (Cd) and nitric oxide (NO) donor (sodium nitroprusside, SNP) alone or together on green alga Coccomyxa subellipsoidea was studied. Stimulatory impact of Cd and SNP on NO formation was synergistic in combined treatments and correlated with the increase of ascorbic acid. Exogenously applied Cd concentration (and not SNP co-application) was the main determinant of Cd uptake, phytochelatin 2, and reduced (GSH) and oxidized (GSSG) glutathione amounts. Glutathione reductase activity was depleted while ascorbate peroxidase activity enhanced by high SNP under both Cd concentrations. This may be related to the appearance of oxidative stress detected by fluorescence microscopy of oxygen radicals and lipid peroxidation in high SNP and/or Cd treatments. Among organic acids, the increase in pyruvate indicates enhancement of glycolysis under Cd excess, while quantitative changes of malic acid evoked by SNP co-application rather correlated with Cd accumulation. Relatively negligible alterations of phenolic metabolites (benzoic acids and total soluble phenols) and free amino acids were also observed. Overall, the generation of NO was not sufficient to counteract the oxidative stress in high Cd or SNP doses but our data clearly show that NO regulates accumulation of ascorbic acid while Cd uptake correlates with the amount of thiols.

The Role of Sulfur in Increasing Guinea Grass Tolerance of Copper Phytotoxicity

Soil pollution with trace elements is a growing problem with serious environmental impacts and developing strategies to reduce those impacts is a high priority. The objectives of this study were to assess the role of sulfur (S) in reducing the phytotoxic effects of copper (Cu) and the appearance of oxidative stress due to excess Cu in the growth medium and to assess the potential of guinea grass for Cu phytoremediation. The experiment was carried out in a greenhouse, where the forage grass Panicum maximum cv. Tanzânia was grown with a nutrient solution containing combinations of three S concentrations (0.1, 2, and 4 mmol L−1) and four Cu concentrations (0.3, 100, 500, and 1,000 μmol L−1) using a 3 × 4 factorial design in complete randomized blocks with four replicates. The following variables were measured: shoot and root dry mass production, leaf and tiller number, S and Cu concentrations in diagnostic leaves and roots, H2O2, lipid peroxidation, and proline levels in the diagnostic leaves. Very high Cu availability (1,000 μmol L−1) that resulted in Cu concentration higher than 60 mg kg−1 in diagnostic leaves caused more than 50 % reduction in shoot and root dry mass production about 30–40 % in the number of leaves and tillers around 20 % increase in lipid peroxidation and more than 10 times increase in proline production. Plants properly fed with S showed mitigation to Cu toxicity. Guinea grass showed promise as an agent in the phytoremediation of Cu-polluted areas.

Melatonin Prevents Postovulatory Oocyte Aging in the Mouse and Extends the Window for Optimal Fertilization In Vitro1

The quality of metaphase II oocytes deteriorates rapidly following ovulation as the result of an aging process associated with impaired fertilizing potential, disrupted developmental competence, and increased likelihood of embryonic resorption. Because oxidative stress accelerates the onset of apoptosis in oocytes and influences their capacity for fertilization, this study aimed to characterize the significance of such stress in the postovulatory aging of mouse oocytes in vitro. We investigated the ability of the potent antioxidant melatonin to arrest the aging process when used to supplement oocyte culture medium. This study demonstrated that oxidative stress may occur in oocytes after as little as 8 h in culture and coincides with the appearance of early apoptotic markers such as phosphatidylserine externalization, followed 16 h later by caspase activation (P < 0.05) and morphological evidence of oocyte senescence. Importantly, supplementation of oocyte culture medium with 1 mM melatonin was able to significantly relieve the time-dependent appearance of oxidative stress in oocytes (P < 0.05) and, as a result, significantly delay the onset of apoptosis (P < 0.05). Furthermore, melatonin supplementation extended the optimal window for fertilization of oocytes aged for 8 and 16 h in vitro (P < 0.05) and significantly improved the quality of the resulting embryos (P < 0.01). We conclude that melatonin may be a useful tool in a clinical setting to prevent the time-dependent deterioration of oocyte quality following prolonged culture in vitro.