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Background: Cobalt is an important metal cofactor of many living cells. However, excessive cobalt is toxic and can cause cell death and even several diseases in humans. Saccharomyces cerevisiae is a useful tool for studying metal homeostasis and many of the genes and pathways are highly conserved in higher eukaryotes including humans., Methods: The intracellular cobalt and reactive oxygen species (ROS) levels were measured by an atomic absorption spectrometer and DHE staining method, respectively. The expression of genes involved in scavenging oxidative stress was tested by qPCR method, while the expression of UPRE-lacZ report gene was analyzed via β-galactosidase activity assay., Results: Using a genome-scale genetic screen, 153 cobalt-sensitive and 37 cobalt-tolerant gene deletion mutants were identified from Saccharomyces cerevisiae. We showed that 101 of the cobalt-sensitive mutants accumulated higher intracellular cobalt compared to wild-type. The intracellular ROS levels in 112 of the mutants were induced by cobalt, which might be caused by the decreased expression of genes involved in scavenging oxidative stress in response to cobalt. Moreover, more than one-third of the cobalt-sensitive mutants were also sensitive to tunicamycin, and cobalt stress might induce the unfolded protein response (UPR) through serine/threonine kinase and endoribonuclease Ire1., Conclusions: This study reinforced the fact that cobalt toxicity might be due to the high intracellular cobalt and ROS levels, and the endoplasmic reticulum stress responses induced by cobalt., General Significance: Elucidating the toxicity mechanisms of cobalt stress response will help reveal new routes for the treatment of the diseases induced by cobalt., (Copyright © 2020. Published by Elsevier B.V.)

The excessive accumulation of cobalt (Co) in plant tissues severely impairs plant growth that ultimately reduces the yield. However, melatonin (MT) has been known to mediate the abiotic stress tolerance in plants. The present study aimed at investigating the protective mechanisms of exogenously applied MT (0, 50 and 100 μM) under Co (0, 100, 200 and 300 μM) stress by focusing on morpho-physiological, biochemical and cellular characterizations of Brassica napus plants. Cobalt (300 μM) alone treatment drastically inhibited the stomatal conductance, plant height (45%), leaf area (30%), free amino acid (139%), relative electrolyte leakage (109%), and total soluble sugars (71%), compared with the control. However, the exogenous supply of MT notably minimized the oxidative damage, lipid peroxidation and maintained the membrane integrity under Co-toxicity by restricting the overproduction of ROS (H2O2 and O2•), and MDA in leaves and roots. Melatonin significantly enhanced the activities of ROS-scavenging antioxidant enzymes, secondary metabolism-related phenylalanine ammonia lyase (PAL), polyphenol oxidase (PPO), stress-responsive genes (heat shock protein as HSP-90, methyl transferase as MT) and regulated the Co-transporters, especially in roots. These findings indicated that an exogenous supply of MT improve the plant morphology, photosynthetic apparatus, osmotic adjustments, and antioxidant defense systems by enhancing the Co-detoxification in B. napus plants.

The present investigation was undertaken to evaluate the toxic effects of CoCl 2 -induced hepatotoxicity and fatty acid changes in juvenile Cyprinus carpio. Fish were divided into six experimental groups in duplicate. The first group served as controls. The second group received the lowest exposure dose at 2.5 µg/L. In the third group, fish were exposed to 25 µg/L of CoCl 2 . The fourth group was exposed to 50 µg/L of CoCl 2 . The last two groups were exposed to the highest doses, 100 and 500 µg/L of CoCl 2 . Total antioxidant activities were estimated using a colorimetric method. Liver fatty acid compositions were analyzed by high-performance gas chromatography (GC). Hepatopathy was identified through microscopic analysis. Exposure of C. carpio to CoCl 2 resulted in hepatotoxicity, indicated by increased levels of malondialdehyde (MDA), hydrogen peroxide (H 2 O 2 ), protein carbonyls (PCO), and alterations in the ferric reducing antioxidant power system (FRAP). Superoxide dismutase (SOD), glutathione-S-transferase (GST), glutathione peroxidase (GPx), reduced glutathione (GSH), metallothioneins (MTs), and low thiol levels (L-SH) significantly increased, particularly under exposure to the highest CoCl 2 doses (100 and 500 µg/L). Acetylcholinesterase activity decreased significantly in C. carpio exposed to graded CoCl 2 doses. Additionally, there was a decrease in polyunsaturated fatty acids (PUFA), primarily n-3 PUFA, docosahexaenoic acid (DHA), and eicosapentaenoic acid (EPA), while an increase in monounsaturated (MUFA) and saturated fatty acids (SFA), including palmitic (C16:0), stearic (C18:0), palmitoleic (C16:1), and oleic (C18:1) acids, was observed. Histopathological examination of the liver confirmed hepatopathy revealing characteristic tissue changes such as leucocyte infiltration, hepatic cell membrane degradation, vacuolization, and lipid inclusions. The study provided ethnophysiology insights into the responses of C. carpio to CoCl 2 -induced oxidative stress and lipidomic alteration, underscoring its potential as a bioindicator for assessing environmental impacts and metal contamination., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Cobalt (Co) commonly co-exists with copper (Cu) in natural soils, but the information about their combined effects on plants is poorly available. In this study, we hydroponically investigated the combined effects of Co and Cu on two barley genotypes differing in Co toxicity tolerance to reveal the interaction pattern of these two metals. The results showed that single treatment of Co or Cu at the dose of 100 μM led to a significant decrease of growth and photosynthetic rate, and a significant increase of lipid peroxidation, ROS radicals as well as anti-oxidative enzyme (SOD, CAT and GR) activities and glutathione content, with the extent of effect being less in Yan66 than Ea52. The combined treatment of Co and Cu alleviated the toxicity of both metals in comparison with each metal treatment alone, as reflected by improved growth and photosynthesis, and much slight oxidative stress. The alleviation of metal toxicity upon combined treatment is mainly attributed to a drastic reduction of Co uptake and its translocation from roots to shoots. It may be suggested that interaction of Co and Cu on their uptake and movement in plants is antagonistic. • The interaction of Co and Cu is antagonistic. • The combined treatment of Cu and Co alleviated Co toxicity relative to Co treatment alone. • The alleviation of Co toxicity by combined treatment is attributed to the uptake and transportation of Co in plants. [ABSTRACT FROM AUTHOR]

Cobalt (Co) contamination in soils is becoming a severe issue in environment safety and crop production. Calcium (Ca) , as a macro-nutrient element, shows the antagonism with many divalent heavy metals and the capacity of alleviating oxidative stress in plants. In this study, the protective role of Ca in alleviating Co stress was hydroponically investigated using two barley genotypes differing in Co toxicity tolerance. Barley seedlings exposed to 100 µM Co showed the significant reduction in growth and photosynthetic rate, and the dramatic increase in the contents of reactive oxygen species (ROS), malondialdehyde (MDA), reduced glutathione (GSH) and oxidized glutathione (GSSG), and the activities of anti-oxidative enzymes, with Ea52 (Co-sensitive) being much more affected than Yan66 (Co-tolerant). Addition of Ca in growth medium alleviated Co toxicity by reducing Co uptake and enhancing the antioxidant capacity. The effect of Ca in alleviating Co toxicity was much greater in Yan66 than in Ea52. The results indicate that the alleviation of Co toxicity in barley plants by Ca is attributed to the reduced Co uptake and enhanced antioxidant capacity. [ABSTRACT FROM AUTHOR]

The excessive accumulation of cobalt (Co) in plant tissues severely impairs plant growth that ultimately reduces the yield. However, melatonin (MT) has been known to mediate the abiotic stress tolerance in plants. The present study aimed at investigating the protective mechanisms of exogenously applied MT (0, 50 and 100 μM) under Co (0, 100, 200 and 300 μM) stress by focusing on morpho-physiological, biochemical and cellular characterizations of Brassica napus plants. Cobalt (300 μM) alone treatment drastically inhibited the stomatal conductance, plant height (45%), leaf area (30%), free amino acid (139%), relative electrolyte leakage (109%), and total soluble sugars (71%), compared with the control. However, the exogenous supply of MT notably minimized the oxidative damage, lipid peroxidation and maintained the membrane integrity under Co-toxicity by restricting the overproduction of ROS (H 2 O 2 and O 2 • ), and MDA in leaves and roots. Melatonin significantly enhanced the activities of ROS-scavenging antioxidant enzymes, secondary metabolism-related phenylalanine ammonia lyase (PAL), polyphenol oxidase (PPO), stress-responsive genes (heat shock protein as HSP-90 , methyl transferase as MT) and regulated the Co-transporters, especially in roots. These findings indicated that an exogenous supply of MT improve the plant morphology, photosynthetic apparatus, osmotic adjustments, and antioxidant defense systems by enhancing the Co-detoxification in B. napus plants. [Display omitted] • Cobalt stress drastically inhibited the plant growth and photosynthetic efficiency. • Exogenous supply of melatonin notably minimized Co-toxicity in plants. • Melatonin significantly enhanced the activities of antioxidant enzymes. • Application of MT significantly increased secondary metabolism-related enzymes. • Co-transporters regulated in B. napus roots with exogenously MT application. [ABSTRACT FROM AUTHOR]

In Saccharomyces cerevisiae, vacuolar H + -ATPase (V-ATPase) involved in the regulation of intracellular pH homeostasis has been shown to be important for tolerances to cadmium, cobalt and nickel. However, the molecular mechanism underlying the protective role of V-ATPase against these metals remains unclear. In this study, we show that cadmium, cobalt and nickel disturbed intracellular pH balance by triggering cytosolic acidification and vacuolar alkalinization, likely via their membrane permeabilizing effects. Since V-ATPase plays a crucial role in pumping excessive cytosolic protons into the vacuole, the metal-sensitive phenotypes of the Δvma2 and Δvma3 mutants lacking V-ATPase activity were supposed to result from highly acidified cytosol. However, we found that the metal-sensitive phenotypes of these mutants were caused by increased production of reactive oxygen species, likely as a result of decreased expression and activities of manganese superoxide dismutase and catalase. In addition, the loss of V-ATPase function led to aberrant vacuolar morphology and defective endocytic trafficking. Furthermore, the sensitivities of the Δvma mutants to other chemical compounds (i.e. acetic acid, H 2 O 2 , menadione, tunicamycin and cycloheximide) were a consequence of increased endogenous oxidative stress. These findings, therefore, suggest the important role of V-ATPase in preventing endogenous oxidative stress induced by metals and other chemical compounds., (© 2020 Society for Applied Microbiology and John Wiley & Sons Ltd.)

Abstract: Background: Cobalt has a rare occurrence in nature, but may accumulate in cells to toxic levels. In the present study, we have investigated how the transcription factor Yap1 mediates tolerance to cobalt toxicity. Methods: Fluorescence microscopy was used to address how cobalt activates Yap1. Using microarray analysis, we compared the transcriptional profile of a strain lacking Yap1 to that of its parental strain. To evaluate the extent of the oxidative damage caused by cobalt, GSH was quantified by HPLC and protein carbonylation levels were assessed. Results: Cobalt activates Yap1 under aerobiosis and anaerobiosis growth conditions. This metal generates a severe oxidative damage in the absence of Yap1. However, when challenged with high concentrations of cobalt, yap1 mutant cells accumulate lower levels of this metal. Accordingly, microarray analysis revealed that the expression of the high affinity phosphate transporter, PHO84, a well-known cobalt transporter, is compromised in the yap1 mutant. Moreover, we show that Yap1 is a repressor of the low affinity iron transporter, FET4, which is also known to transport cobalt. Conclusions: Cobalt activates Yap1 that alleviates the oxidative damage caused by this metal. Yap1 partially controls cobalt cellular uptake via the regulation of PHO84. Although FET4 repression by Yap1 has no effect on cobalt uptake, it may be its first line of defense against other toxic metals. General significance: Our results emphasize the important role of Yap1 in mediating cobalt-induced oxidative damages and reveal new routes for cell protection provided by this regulator. [Copyright &y& Elsevier]

Chemical overexposure is a growing environmental risk factor for many medical issues. Cobalt toxicity from environmental, industrial, and medical exposure has previously been linked to neurological impairment. Hence, the current study looked into the neuroprotective potential of curcumin, a natural polyphenol contained in the spice turmeric, against cobalt-induced neurotoxicity. Adult rats were randomly divided into six groups as follows: control, 40 mg/kg cobalt chloride (CoCl2) only, 240 mg/kg curcumin only, 120 mg/kg or 240 mg/kg curcumin, or 100 mg/kg vitamin C co-administered with CoCl2. The administration was via oral route daily for 4 weeks. After that, neurobehavioral tests were undertaken to evaluate short-term spatial memory. Biochemical investigation was performed to determine the hippocampal levels of status via measures of SOD, CAT, GST, and LPO. Furthermore, immunohistochemical assessment of the expression of GFAP and Nrf2 in the hippocampus was carried out. In the CoCl2 group, the results showed altered behavioral responses, a decrease in antioxidant activities, increased expression of GFAP and the number of activated astrocytes, and decreased immunoexpression of Nrf2. These effects were mitigated in the curcumin- and vitamin C–treated groups. These results collectively imply that curcumin enhances memory functions in rats exposed to cobalt possibly by attenuating oxidative responses, mitigating astrocytosis, and modulating Nrf2 signaling. [ABSTRACT FROM AUTHOR]

Objective(s): Cobalt toxicity has become a health concern in recent years, due to overexposure resulting in neurological impairments. With a growing interest in the therapeutic roles of herbs, in toxicity research, it's worth looking into the curative effects of aqueous Prosopis africana seed extract, a plant rich in flavonoids on cobalt-induced neurotoxicity. Materials and Methods: We treated rats with CoCl2 or CoCl2 in combination with aqueous PA seed extract (PAE) orally for 14 days. Control rats received distilled water for the same period. Following treatments, behavioral experiments, analysis for oxidative stress, inflammation, and histological and immunohistochemical analysis were performed. Results: Results revealed that CoCl2 reduced the exploration time, recognition index in the novel object recognition test, percentage spontaneous alternation in the Y-maze tests, and reduced open arm entry and duration in elevated plus-maze. However, treatment with PAE improved these parameters to levels comparable with those of the control group. Furthermore, PAE therapy reduced CoCl2-induced surge in hydrogen peroxide, malondialdehyde, TNF-a and IL-1ß levels in brain homogenate, while also increasing superoxide dismutase and reduced reduced-glutathione activities. CoCl2 exposure resulted in obvious features of neurodegeneration like nuclear disintegration, nuclear shrinkage, and cytoplasmic vacuolations of the cells of the hippocampus and amygdala, with an increased expression of GFAP. The hippocampal and amygdala histology improved after PAE administration, while exacerbated GFAP expressions were attenuated. Conclusion: These findings imply that PAE may be anxiolytic and can help reduce cognitive impairments and hippocampal damage caused by CoCl2 neurotoxicity, via mechanisms that involve attenuation of oxidative stress and inflammation. [ABSTRACT FROM AUTHOR]

Background: With the re-popularity of metal-on-metal (MoM) bearing in recent years, the cobalt toxicity has been a cause for concern in the total hip replacement surgery by both physicians and patients. Methods: MG-63 cell line was cultured in vitro and incubated with cobalt (II) chloride (CoCl2) and/or with astaxanthin (ASX) for 24 h. MTT assay was conducted to evaluate the cell viability after cobalt exposure and ASX treatment. Fluorescence-activated cell sorting (FACS) analysis was performed to examine the reactive oxygen species (ROS) level. Quantitative real-time polymerase chain reaction (PCR) was adopted to determine the mRNA levels of related targets. And western blot analysis was used to examine the protein expressions. One-way ANOVA with posttest Newman-Keuls multiple comparisons was adopted to analysis all the obtained data. Results: In the current study, ASX exhibited significant protective effect against the Co(II)-induced cytotoxicity in MG-63 cell line. We also found that ASX protected the cells against Co-induced apoptosis by regulating the expression of Bcl-2 family proteins. Besides, heme oxygenase 1 (HO-1) could be activated by Co exposure; ASX treatment significantly inhibited HO-1 activation, suppressing the oxidative stress induced by Co exposure. Moreover, c-Jun N-terminal Kinase (JNK) phosphorylation was shown to participate in the signaling pathway of the protective effect of ASX. However, knockdown of JNK expression by siRNA transfection or JNK inhibitor SP600125 treatment did not affect the protective effect of ASX against cobalt cytotoxicity in MG-63 cells. Conclusions: ASX mitigated cobalt cytotoxicity in the MG-63 cells by modulating the oxidative stress. And ASX could be a promising therapy against cobalt toxicity in the hip articulation surgery. [ABSTRACT FROM AUTHOR]

Nitric oxide (NO) is a multifunctional signalling molecule involved in the regulation of plant ontogenesis and adaptation to different adverse environmental factors, in particular to osmotic stress. Understanding NO-induced plant protection is important for the improvement of plant stress tolerance and crop productivity under global climate changes. The root system is crucial for plant survival in a changeable environment. Damages that it experiences under water deficit conditions during the initial developmental periods seriously affect the viability of the plants. This work was devoted to the comparative analysis of the pretreatment of wheat seedlings through the root system with NO donor sodium nitroprusside (SNP) for 24 h on various parameters of redox homeostasis under exposure to osmotic stress (PEG 6000, 12%) over 0.5–24 h. The active and exhausted solutions of SNP, termed as (SNP/+NO) and (SNP/−NO), respectively, were used in this work at a concentration of 2 × 10−4 M. Using biochemistry and light microscopy methods, it has been revealed that osmotic stress caused oxidative damages and the disruption of membrane cell structures in wheat roots. PEG exposure increased the production of superoxide (O2•−), hydrogen peroxide (H2O2), malondialdehyde (MDA), and the levels of electrolyte leakage (EL) and lipid peroxidation (LPO). Stress treatment enhanced the activities of superoxide dismutase (SOD), ascorbate peroxidase (APX), catalase (CAT), the excretion of proline, and the rate of cell death and inhibited their division. Pretreatment with (SNP/+NO) decreased PEG-induced root damages by differently regulating the antioxidant enzymes under stress conditions. Thus, (SNP/+NO) pretreatment led to SOD, APX, and CAT inhibition during the first 4 h of stress and stimulated their activity after 24 h of PEG exposure when compared to SNP-untreated or (SNP/−NO)-pretreated and stress-subjected plants. Osmotic stress triggered the intense excretion of proline by roots into the external medium. Pretreatment with (SNP/+NO) in contrast with (SNP/−NO) additionally increased stress-induced proline excretion. Our results indicate that NO is able to mitigate the destructive effects of osmotic stress on the roots of wheat seedlings. However, the mechanisms of NO protective action may be different at certain periods of stress exposure. [ABSTRACT FROM AUTHOR]

Patients suffering from chronic mountain sickness (CMS) have excessive erythrocytosis. Low −level cobalt toxicity as a likely contributor has been demonstrated in some subjects. We performed a randomized, placebo controlled clinical trial in Cerro de Pasco, Peru (4380 m), where 84 participants with a hematocrit (HCT) ≥65% and CMS score > 6, were assigned to four treatment groups of placebo, acetazolamide (ACZ, which stimulates respiration), N -acetylcysteine (NAC, an antioxidant that chelates cobalt) and combination of ACZ and NAC for 6 weeks. The primary outcome was change in hematocrit and secondary outcomes were changes in PaO 2 , PaCO 2 , CMS score, and serum and urine cobalt concentrations. The mean (±SD) hematocrit, CMS score and serum cobalt concentrations were 69 ± 4%, 9.8 ± 2.4 and 0.24 ± 0.15 μg/l, respectively for the 66 participants. The ACZ arm had a relative reduction in HCT of 6.6% vs. 2.7% (p = 0.048) and the CMS score fell by 34.9% vs. 14.8% (p = 0.014) compared to placebo, while the reduction in PaCO 2 was 10.5% vs. an increase of 0.6% (p = 0.003), with a relative increase in PaO 2 of 13.6% vs. 3.0%. NAC reduced CMS score compared to placebo (relative reduction of 34.0% vs. 14.8%, p = 0.017), while changes in other parameters failed to reach statistical significance. The combination of ACZ and NAC was no better than ACZ alone. No changes in serum and urine cobalt concentrations were seen within any treatment arms. ACZ reduced polycythemia and CMS score, while NAC improved CMS score without significantly lowering hematocrit. Only a small proportion of subjects had cobalt toxicity, which may relate to the closing of contaminated water sources and several other environmental protection measures. [ABSTRACT FROM AUTHOR]

The mechanisms underlying cobalt toxicity in aquatic species in general and cnidarians in particular remain poorly understood. Herein we investigated cobalt toxicity in a Hydra model from morphological, histological, developmental, and molecular biological perspectives. Hydra, exposed to cobalt (0-60 mg/L), were altered in morphology, histology, and regeneration. Exposure to standardized sublethal doses of cobalt impaired feeding by affecting nematocytes, which in turn affected reproduction. At the cellular level, excessive ROS generation, as the principal mechanism of action, primarily occurred in the lysosomes, which was accompanied by the upregulation of expression of the antioxidant genes SOD, GST, GPx, and G6PD. The number of Hsp70 and FoxO transcripts also increased. Interestingly, the upregulations were higher in the 24-h than in the 48-h time-point group, indicating that ROS overwhelmed the cellular defense mechanisms at the latter time-point. Comet assay revealed DNA damage. Cell cycle analysis indicated the induction of apoptosis accompanied or not by cell cycle arrest. Immunoblot analyses revealed that cobalt treatment triggered mitochondria-mediated apoptosis as inferred from the modulation of the key proteins Bax, Bcl-2, and caspase-3. From this data, we suggest the use of Hydra as a model organism for the risk assessment of heavy metal pollution in aquatic ecosystems. [ABSTRACT FROM AUTHOR]

Cobalt nanoparticles (NPs) when released into the air during industrial processes, can enter the lungs through inhalation, leading to potential toxicity and respiratory issues. The mechanism of cobalt toxicity is not well understood and needs further investigation. We, therefore, studied the effects of two kinds of cobalt-based nanoparticles (NPs) on lung cells. These NPs were Co NPs (i.e. Cobalt NPs) and Co-Fe NPs (i.e. CoFe 2 O 4 NPs) that were similar in size and shape but slightly differed for the surface iron composition. The average size of Co NPs was 28 ± 18 nm, and that of Co-Fe was 26 ± 13 nm. We exposed the cells to the NPs for 24 h and measured their viability by MTT assay and CalceinAM fluorescence imaging. Potential induction of reactive oxygen species (ROS) was detected by probes DHE specific for superoxide (O 2 •–) and DCFH-DA for hydrogen peroxide (H 2 O 2). Antioxidant glutathione (GSH) quantification was followed by measuring apoptotic/necrotic potential. Using Co NPs and Co-Fe NPs, we measured the IC50 for cell growth in A549 cells after 24 h of exposure. The values were 79 μg/mL and 163 μg/mL, respectively. We also observed that both NPs induced ROS and reduced the fluorescence of CalceinAM in the cells, but Co NPs had a stronger effect than Co-Fe NPs. This was correlated with the production of O 2 – by the NPs, which was higher for Co NPs than for Co-Fe NPs. On the other hand, H 2 O 2 production was higher for Co-Fe NPs than for Co NPs. Our study suggests that the main cause of differential O 2 – production is the differential release Co2+ ion due to surface modification resulting in differential quenching of green (CalceinAM) fluorescence by both NPs. Both NPs induced apoptosis mode of cell death. Our data from the use of naïve and surface-modified cobalt-based NPs, suggest that NAC can protect cells from cobalt-based NP toxicity by not only restoring cellular GSH levels but also by chelating released Co2+ ions from the NPs surfaces. Additionally, this study for the first time to our knowledge indicates that CalceinAM alone is not sufficient to assess the toxicity of cobalt-based NPs. Other methods should be used to confirm the cytotoxicity data of cobalt-based NPs. [ABSTRACT FROM AUTHOR]

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Background: Metal-on-metal (M-M) total hip arthroplasty (THA) has shown adverse reactions to metal debris, abnormal soft-tissue reactions, and high blood metal ion levels. This study aims to: (1) assess whether the toxicity of high levels of ions is related to altered oxidative stress and (2) evaluate tribological factors related to increased blood levels of chromium (Cr) and cobalt (Co) ions. Methods: A cross-sectional analytical descriptive study was conducted on 75 patients. A total of 25 underwent M-M THA, 25 ceramic-on-metal (C-M) THA, and 25 were on the THA waiting list. Ion metallic levels in blood, oxidative stress, physical activity, and implant position were compared. Results: In the M-M group, Co and Cr levels were significantly higher than those found in the C-M group and the control group (p < 0.01). We found no differences in terms of oxidative stress between the groups. Also, we did not find a correlation between metal blood levels and oxidative stress indicators, the physical activity of the patients or the position of the implants between groups. Conclusions: The use of M-M bearing surfaces in THA raises the levels of metals in the blood without modifying oxidative stress regardless of the physical activity levels of the patients. Therefore, although patients with M-M bearings require close monitoring, it does not seem necessary to recommend the restriction of physical activity in patients with M-M or C-M arthroplasties. [ABSTRACT FROM AUTHOR]

Metal-on-metal hip arthroplasty has been performed with increasing frequency throughout the world, particularly in younger and more active patients, including women of childbearing age. The potential toxicity of cobalt exposure on fetus is concerned since cobalt ions generated by metal-on-metal bearings can traverse the placenta and be detected in fetal blood and amniotic fluid. This study examined the effects of cobalt exposure on early embryonic development and the mechanisms underlying its toxicity. Zebrafish embryos were exposed to a range of cobalt concentrations (0-100 mg/L) between 1 and 144 h postfertilization. The survival and early development of embryos were not significantly affected by cobalt at concentrations <100 μg/L. However, embryos exposed to higher concentrations (>100 μg/L) displayed reduced survival rates and abnormal development, including delayed hatching, aberrant morphology, retarded growth, and bradycardia. Furthermore, this study examined oxidative stress and apoptosis in embryos exposed to cobalt at concentrations of 0-500 μg/L. Lipid peroxidation levels were increased in cobalt-treated embryos at concentrations of 100 and 500 μg/L. The mRNA levels of catalase, superoxide dismutase 2, p53, caspase-3, and caspase-9 genes were upregulated in a dose-dependent manner. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assays also revealed abnormal apoptotic signals in the brain, trunk, and tail when treated with 500 μg/L cobalt. These data suggest that oxidative stress and apoptosis are associated with cobalt toxicity in zebrafish embryos.

Ellagic acid (EA) is a polyphenol extracted from many plants. EA modulates inflammatory mediators via antioxidant mechanisms, such as catalase (CAT) activities, superoxide dismutase (SOD), enhancement, increase in glutathione (GSH), and lipid peroxidation (LPO) suppression. EA has anti‐apoptotic properties that are thought to be mediated by regulating the expression of B‐cell lymphoma 2 (Bcl‐2), Bcl‐2‐associated X protein (Bax), and caspase‐3. In this article, we surveyed the literature dealing with the protective effects of EA against different heavy metals, drugs, and natural toxins. The findings indicated that EA has remarkable protective properties against various toxicants. Its protective effects were mostly mediated via normalizing lipid metabolism, oxidative stress, and inflammatory mediators, for example, tumor necrosis factor‐α (TNF‐α), interleukin‐6 (IL‐6), and IL‐1β. The results of this study showed that EA has significant protective effects against a varied range of compounds, either chemical or natural. These effects are mainly mediated via intensifying the antioxidant defense system. However, other mechanisms such as inhibition of inflammatory responses and suppression of apoptosis are important. [ABSTRACT FROM AUTHOR]

Cobalt can be toxic and the way cells adapt to its presence is largely unknown. Here we carried out a transcriptomic analysis of Escherichia coli exposed to cobalt. A limited number of genes were either up- or downregulated. Upregulated genes include the isc and the nfuA genes encoding Fe/S biogenesis assisting factors, and the rcnA gene encoding a cobalt efflux system. Downregulated genes are implicated in anaerobic metabolism (narK, nirB, hybO, grcA), metal transport (feoB, nikA), sulfate/thiosulfate import (cysP), and one is of unknown function (yeeE). Cobalt regulation of isc, nfuA, hybO, cysP and yeeE genes was found to involve IscR, a Fe/S transcriptional regulator. Previously, the Suf Fe/S biogenesis machinery was found to be important for cobalt stress adaptation, but suf genes did not show up in the microarray analysis. Therefore, we used qRT-PCR analysis and found that cobalt induced the suf operon expression. Moreover, kinetic analysis of the cobalt-mediated induction of the suf operon expression allowed us to propose that cobalt toxicity is caused first by impaired Fe/S biogenesis, followed by decreased iron bioavailability and eventually oxidative stress., (© 2010 Society for Applied Microbiology and Blackwell Publishing Ltd.)

Metal-on-metal hip arthroplasty has been performed with increasing frequency throughout the world, particularly in younger and more active patients, including women of childbearing age. The potential toxicity of cobalt exposure on fetus is concerned since cobalt ions generated by metal-on-metal bearings can traverse the placenta and be detected in fetal blood and amniotic fluid. This study examined the effects of cobalt exposure on early embryonic development and the mechanisms underlying its toxicity. Zebrafish embryos were exposed to a range of cobalt concentrations (0-100 mg/L) between 1 and 144 h postfertilization. The survival and early development of embryos were not significantly affected by cobalt at concentrations <100 μg/L. However, embryos exposed to higher concentrations (>100 μg/L) displayed reduced survival rates and abnormal development, including delayed hatching, aberrant morphology, retarded growth, and bradycardia. Furthermore, this study examined oxidative stress and apoptosis in embryos exposed to cobalt at concentrations of 0-500 μg/L. Lipid peroxidation levels were increased in cobalt-treated embryos at concentrations of 100 and 500 μg/L. The mRNA levels of catalase, superoxide dismutase 2, p53, caspase-3, and caspase-9 genes were upregulated in a dose-dependent manner. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assays also revealed abnormal apoptotic signals in the brain, trunk, and tail when treated with 500 μg/L cobalt. These data suggest that oxidative stress and apoptosis are associated with cobalt toxicity in zebrafish embryos. [ABSTRACT FROM AUTHOR]

Phenolic acid is a well-known allelochemical, but also a pollutant in soil and water impeding crop production. Biochar is a multifunctional material widely used to mitigate the phenolic acids allelopathic effect. However, phenolic acid absorbed by biochar can still be released. In order to improve the removal efficiency of phenolic acids by biochar, the biochar-dual oxidant (BDO) composite particles were synthesized in this study, and the underlying mechanism of the BDO particles in ameliorating p-coumaric acid (p-CA) oxidative damage to tomato seed germination was revealed. Upon p-CA treatment, the BDO composite particles application increased the radical length, radical surface area, and germination index by 95.0%, 52.8%, and 114.6%, respectively. Compared to using biochar or oxidants alone, the BDO particles addition resulted in a higher removal rate of p-CA and produced more O2•−, HO•, SO4•− and 1O2 radicals via autocatalytic action, suggesting that BDO particles removed phenolic acid by both adsorption and free radical oxidation. The addition of BDO particles maintained the levels of the antioxidant enzyme activity close to the control, and reduced the malondialdehyde and H2O2 by 49.7% and 49.5%, compared to the p-CA treatment. Integrative metabolomic and transcriptomic analyses revealed that 14 key metabolites and 62 genes were involved in phenylalanine and linoleic acid metabolism, which increased dramatically under p-CA stress but down-regulated with the addition of BDO particles. This study proved that the use of BDO composite particles could alleviate the oxidative stress of phenolic acid on tomato seeds. The findings will provide unprecedented insights into the application and mechanism of such composite particles as continuous cropping soil conditioners. [ABSTRACT FROM AUTHOR]

Ferroptosis is a new type of iron-dependent cell death induced by a failure of the lipid repair protein GPX4 or the Xc- antiporter, which is essential for glutathione production. Some heavy metals such as arsenic (As), cobalt (Co), cadmium (Cd), iron (Fe), magnesium (Mg), manganese (Mn), nickel (Ni), mercury (Hg) as well as zinc (Zn) are shown to induce ferroptotic cell death involving the generation of oxidative stress, mitochondrial dysfunctioning, lipid peroxidation, and several other cellular etiologies. However, selenium (Se) treatment has been shown to enhance adaptive transcription responses to protect cells from ferroptosis. Heavy metals like Cadmium exposure activated ALK4/5 signaling via Smad3 and Akt signaling which leads to cell death mechanism. Continuous exposure to a small dose of mercury can damage tissues, and methylmercury bind to sulfhydryl proteins and GSH, this elevates oxidative stress, free radical accumulation, glutathione depletion, mitochondrial damage, and inhibited the nuclear factor-κB pathway which leads to ferroptotic cell death. Animals exposed to nickel and cobalt may have increased lipid peroxidation which can induce ferroptosis. Glutathione depletion is caused by Zn intoxication and exposure to manganese. These metals are systemic toxins that have been shown adverse effects on humans. Ferroptosis has recently been related to several pathological disorders, including, Alzheimer's disease, Parkinson's disease, Huntington's disease, as well as cardiovascular disease, and any type of cancer. For these disorders and some heavy metal toxicity, ferroptosis suppression needs to be looked upon as a promising therapeutic choice. [ABSTRACT FROM AUTHOR]

Objective(s): Cobalt toxicity has become a health concern in recent years, due to overexposure resulting in neurological impairments. With a growing interest in the therapeutic roles of herbs, in toxicity research, it’s worth looking into the curative effects of aqueous Prosopis africana seed extract, a plant rich in flavonoids on cobalt-induced neurotoxicity. Materials and Methods: We treated rats with CoCl2 or CoCl2 in combination with aqueous PA seed extract (PAE) orally for 14 days. Control rats received distilled water for the same period. Following treatments, behavioral experiments, analysis for oxidative stress, inflammation, and histological and immunohistochemical analysis were performed. Results: Results revealed that CoCl2 reduced the exploration time, recognition index in the novel object recognition test, percentage spontaneous alternation in the Y-maze tests, and reduced open arm entry and duration in elevated plus-maze. However, treatment with PAE improved these parameters to levels comparable with those of the control group. Furthermore, PAE therapy reduced CoCl2-induced surge in hydrogen peroxide, malondialdehyde, TNF-α and IL-1β levels in brain homogenate, while also increasing superoxide dismutase and reduced reduced-glutathione activities. CoCl2 exposure resulted in obvious features of neurodegeneration like nuclear disintegration, nuclear shrinkage, and cytoplasmic vacuolations of the cells of the hippocampus and amygdala, with an increased expression of GFAP. The hippocampal and amygdala histology improved after PAE administration, while exacerbated GFAP expressions were attenuated. Conclusion: These findings imply that PAE may be anxiolytic and can help reduce cognitive impairments and hippocampal damage caused by CoCl2 neurotoxicity, via mechanisms that involve attenuation of oxidative stress and inflammation.

The effect of two concentrations of cobalt (Co 2+ ) on photosynthetic activity and antioxidative response in Lemna minor L. were assessed 24, 48 and 72 h after the start of the exposure. Higher concentration of cobalt (1 mM) induced growth inhibition while lower concentration (0.01 mM) increased photosynthetic pigments content. Analysis of chlorophyll a fluorescence transients revealed high sensitivity of photosystem II primary photochemistry to excess of Co 2+ especially at the higher concentration where decreased electron transport beyond primary quinone acceptor Q A − and impaired function of oxygen evolving complex (OEC) was observed. Due to impairment of OEC, oxygen production was decreased at higher Co 2+ concentration. Activity of superoxide dismutase was mainly inhibited while lipid peroxidation increased, at both concentrations, indicating that cobalt-induced oxidative damage after short exposure and moreover, susceptibility of the membranes in the cell to cobalt toxicity. Results obtained in this study suggest possible application of used parameters as tools in assessment of early damage caused by metals. [ABSTRACT FROM AUTHOR]

Fungal response to any stress is intricate, specific, and multilayered, though it employs only a few evolutionarily conserved regulators. This comes with the assumption that one regulator operates more than one stress-specific response. Although the assumption holds true, the current understanding of molecular mechanisms that drive response specificity and adequacy remains rudimentary. Deciphering the response of fungi to oxidative stress may help fill those knowledge gaps since it is one of the most encountered stress types in any kind of fungal niche. Data have been accumulating on the roles of the HOG pathway and Yap1- and Skn7-related pathways in mounting distinct and robust responses in fungi upon exposure to oxidative stress. Herein, we review recent and most relevant studies reporting the contribution of each of these pathways in response to oxidative stress in pathogenic and opportunistic fungi after giving a paralleled overview in two divergent models, the budding and fission yeasts. With the concept of stress-specific response and the importance of reactive oxygen species in fungal development, we first present a preface on the expanding domain of redox biology and oxidative stress. [ABSTRACT FROM AUTHOR]

The kidney is the main organ that senses changes in systemic oxygen tension, but it is also the key detoxification, transit and excretion site of transition metals (TMs). Pivotal to oxygen sensing are prolyl-hydroxylases (PHDs), which hydroxylate specific residues in hypoxia-inducible factors (HIFs), key transcription factors that orchestrate responses to hypoxia, such as induction of erythropoietin (EPO). The essential TM ion Fe is a key component and regulator of the hypoxia–PHD–HIF–EPO (HPHE) signaling axis, which governs erythropoiesis, angiogenesis, anaerobic metabolism, adaptation, survival and proliferation, and hence cell and body homeostasis. However, inadequate concentrations of essential TMs or entry of non-essential TMs in organisms cause toxicity and disrupt health. Non-essential TMs are toxic because they enter cells and displace essential TMs by ionic and molecular mimicry, e. g. in metalloproteins. Here, we review the molecular mechanisms of HPHE interactions with TMs (Fe, Co, Ni, Cd, Cr, and Pt) as well as their implications in renal physiology, pathophysiology and toxicology. Some TMs, such as Fe and Co, may activate renal HPHE signaling, which may be beneficial under some circumstances, for example, by mitigating renal injuries from other causes, but may also promote pathologies, such as renal cancer development and metastasis. Yet some other TMs appear to disrupt renal HPHE signaling, contributing to the complex picture of TM (nephro-)toxicity. Strikingly, despite a wealth of literature on the topic, current knowledge lacks a deeper molecular understanding of TM interaction with HPHE signaling, in particular in the kidney. This precludes rationale preventive and therapeutic approaches to TM nephrotoxicity, although recently activators of HPHE signaling have become available for therapy. [ABSTRACT FROM AUTHOR]

Heavy metals is a collective term describing metals and metalloids with a density higher than 5 g/cm3. Some of them are essential micronutrients; others do not play a positive role in living organisms. Increased anthropogenic emissions of heavy metal ions pose a serious threat to water and land ecosystems. The mechanism of heavy metal toxicity predominantly depends on (1) their high affinity to thiol groups, (2) spatial similarity to biochemical functional groups, (3) competition with essential metal cations, (4) and induction of oxidative stress. The antioxidant response is therefore crucial for providing tolerance to heavy metal-induced stress. This review aims to summarize the knowledge of heavy metal toxicity, oxidative stress and antioxidant response in eukaryotic algae. Types of ROS, their formation sites in photosynthetic cells, and the damage they cause to the cellular components are described at the beginning. Furthermore, heavy metals are characterized in more detail, including their chemical properties, roles they play in living cells, sources of contamination, biochemical mechanisms of toxicity, and stress symptoms. The following subchapters contain the description of low-molecular-weight antioxidants and ROS-detoxifying enzymes, their properties, cellular localization, and the occurrence in algae belonging to different clades, as well as the summary of the results of the experiments concerning antioxidant response in heavy metal-treated eukaryotic algae. Other mechanisms providing tolerance to metal ions are briefly outlined at the end. [ABSTRACT FROM AUTHOR]

Inspite of various health warnings from Government and health organizations, Calcium carbide (CaC2) is still the most commonly and widely used artificial fruit ripener, probably due to its easy availability, low cost and convenience of usage. Assessment of the hazardous effects of the CaC2 applications for fruit ripening has been a matter of interest since long. Several in vivo studies have reported the toxicological outcomes such as histopathological changes in lungs and kidneys, haematological and immunological responses, upon exposure with CaC2. However, a well-controlled study investigating the effects of CaC2 under in-vitro setup was lacking. Hence, this study has been conducted to explore the toxicity associated cellular events in L929 cells exposed with varying concentrations of CaC2 (0.00312–0.2 μg/μl) for 24 h exposure time. A 23.14% reduction in cell viability was observed at the highest dose of CaC2. A similar trend in cellular stress levels at 0.2 μg/μl dose was observed in terms of rounded cellular morphology and decreased adherence as compared to the control. Furthermore, Annexin V FITC/PI staining and subsequent confocal imaging revealed a similar trend of CaC2 induced apoptosis in a dose dependent manner. A gradual elevation of intracellular ROS has also been observed up to 0.025 μg/μl dose. Thus, the study concludes that short term CaC2 exposure may increase the cellular oxidative stress and disturb the redox balance of the cell which then undergoes apoptosis. The study concludes that the exposure of CaC2 can be associated with severe diseases and suggests to stop the uses of CaC2 as fruit ripening agent. [ABSTRACT FROM AUTHOR]

Cobalt (Co) is widely used in many industrial fields such as batteries and paints. Cobalt, a dangerous heavy metal, can be found in high concentrations in natural and human habitats. Although cobalt is an important micronutrient, it is toxic to living organisms when exposed to high amounts. Carob (Ceratonia siliqua L.) is a tree native to The Mediterranean region. Carob bean, which has high nutritional and economic value, is used against cardiovascular and gastrointestinal diseases. In addition, the antioxidant properties of carob are gaining importance in recent years. In this study, the protective effects of carob extract against the toxicity of cobalt on Allium cepa L. were investigated. For this purpose, 150 mg/L and 300 mg/L carob extract solutions and 5.5 mg/kg cobalt solutions were applied to A. cepa L. bulbs. Root emergence, weight gain, root elongation, and mitotic index (MI) decreased, while the frequency of chromosomal abnormalities (CAs) and micronucleus (MN) increased as a result of Co application. Furthermore, Co treatment triggered a noticeable rise in the activities of superoxide dismutase (SOD) and catalase (CAT) enzymes as well as the malondialdehyde (MDA) amount and the abnormalities in the meristematic cells. On the other hand, applications of carob extracts mitigated cobalt-induced damages in a dose-dependent manner in all parameters. Therefore, the current study showed that the strong preventive potential of carob extract against phytotoxicity and genotoxicity is caused by Co in a model plant. The protective effects of carob extract on Co-induced toxicity were demonstrated for the first time in terms of reducing genotoxicity and oxidative stress response. [ABSTRACT FROM AUTHOR]

Nickel and cobalt are essential elements that become toxic at high concentrations. Little is known about nickel and cobalt toxicity in aquatic animals. This study aimed to investigate acute and chronic toxicity of nickel and cobalt in Japanese flounder (Paralichthys olivaceous), with emphasis on oxidative stress reactions, histopathological changes, and differences in gene expression. The lethal concentration for 50% mortality (LC 50) in 3 and 8 cm Japanese flounder exposed to nickel for 96 h was found to be 86.2 ± 0.018 and 151.3 ± 0.039 mg/L; for cobalt exposure, LC 50 was 47.5 ± 0.015 and 180.4 ± 0.034 mg/L, respectively. Chronic nickel and cobalt exposure caused different degrees of oxidative enzyme activity changes in gill, liver, and muscle tissues. Erythrocyte deformations were detected after acute or chronic exposure to nickel and cobalt. the nickel and cobalt exposure also caused pathological changes such as spherical swelling over other gill patches, rod-like proliferations in the gill patch epithelial cell layer, and disorder in hepatocyte arrangement, cell swelling, and cytoplasm loosening. RNA-Seq indicated that there were 184 upregulated and 185 downregulated genes in the liver of Japanese flounder exposed to 15 mg/L nickel for 28 d. For cobalt, 920 upregulated and 457 downregulated genes were detected. Among these differentially expressed genes, 162 were shared by both nickel and cobalt exposure. In both nickel and cobalt, pathways including fatty acid elongation, steroid biosynthesis, unsaturated fatty acid biosynthesis, fatty acid metabolism, PPAR signaling, and ferroptosis were significantly enriched. Taken together, these results aided our understanding of the toxicity of nickel and cobalt in aquatic animals. Image 1 • Heterozygous clonal Japanese flounder with genetic similarity of 1.00 were used. • Lethal concentration for 50% mortality that exposed to nickel and cobalt were determined in Japanese flounder. • Chronic nickel and cobalt exposure changed oxidative enzyme activity in Japanese flounder. • Nickel and cobalt induced stress response signaling pathways were explored in Japanese flounder. Chronic nickel and cobalt exposure induced ferroptosis in the liver of Japanese flounder. [ABSTRACT FROM AUTHOR]

Excess cobalt may lead to metallosis, characterized by sensorineural hearing loss, visual, and cognitive impairment, and peripheral neuropathy. In the present study, we sought to address the molecular mechanisms of cobalt-induced neurotoxicity, using Caenorhabditis elegans as an experimental model. Exposure to cobalt chloride for 2 h significantly decreased the survival rate and lifespan in nematodes. Cobalt chloride exposure led to increased oxidative stress and upregulation of glutathione S-transferase 4. Consistently, its upstream regulator skn-1 , a mammalian homolog of the nuclear factor erythroid 2-related factor 2, was activated. Among the mRNAs examined by quantitative real-time polymerase chain reactions, apoptotic activator egl-1 , proapoptotic gene ced-9 , autophagic (bec-1 and lgg-1), and mitochondrial fission regulator drp-1 were significantly upregulated upon cobalt exposure, concomitant with mitochondrial fragmentation, as determined by confocal microscopy. Moreover, drp-1 inhibition suppressed the cobalt chloride-induced reactive oxygen species generation, growth defects, and reduced mitochondrial fragmentation. Our novel findings suggest that the acute toxicity of cobalt is mediated by mitochondrial fragmentation and drp-1 upregulation. [ABSTRACT FROM AUTHOR]

During bioleaching of Cobalt from waste lithium-ion batteries, the biooxidation activity of acidophilic bacteria is inhibited by a high concentration of Co ion in the liquid phase. However, the mechanism for Co2+ toxicity to acidophilic bacteria has not been fully elucidated. In this study, the effects of Co2+ concentration on the biooxidation activity for Fe2+, intracellular reactive oxygen species (ROS) level and antioxidant defense systems in a mixed-culture of acidophilic bacteria (MCAB) were investigated. The results showed that the biooxidation activity of the MCAB was inhibited by Co2+. Furthermore, it was indicated that the intracellular ROS contents of the MCAB under conditions of 0.4 M and 0.6 M Co2+ were 2.60 and 3.34 times higher than that under the condition of 0 M Co2+. The increase in intracellular malondialdehyde content indicated that the oxidative damage was induced by Co2+. Moreover, the antioxidant systems in MCAB were affected by Co2+. It was observed that the Co2+ exposure increased the catalase and glutathione peroxidase activities while reducing the superoxide dismutase activity and the intracellular glutathione (GSH) content. It was found that an exogenous GSH supplementation eliminated excess intracellular ROS and improved the biooxidation activity of the MCAB. [ABSTRACT FROM AUTHOR]

Summary: In Saccharomyces cerevisiae, vacuolar H+‐ATPase (V‐ATPase) involved in the regulation of intracellular pH homeostasis has been shown to be important for tolerances to cadmium, cobalt and nickel. However, the molecular mechanism underlying the protective role of V‐ATPase against these metals remains unclear. In this study, we show that cadmium, cobalt and nickel disturbed intracellular pH balance by triggering cytosolic acidification and vacuolar alkalinization, likely via their membrane permeabilizing effects. Since V‐ATPase plays a crucial role in pumping excessive cytosolic protons into the vacuole, the metal‐sensitive phenotypes of the Δvma2 and Δvma3 mutants lacking V‐ATPase activity were supposed to result from highly acidified cytosol. However, we found that the metal‐sensitive phenotypes of these mutants were caused by increased production of reactive oxygen species, likely as a result of decreased expression and activities of manganese superoxide dismutase and catalase. In addition, the loss of V‐ATPase function led to aberrant vacuolar morphology and defective endocytic trafficking. Furthermore, the sensitivities of the Δvma mutants to other chemical compounds (i.e. acetic acid, H2O2, menadione, tunicamycin and cycloheximide) were a consequence of increased endogenous oxidative stress. These findings, therefore, suggest the important role of V‐ATPase in preventing endogenous oxidative stress induced by metals and other chemical compounds. [ABSTRACT FROM AUTHOR]

Host defenses expose fungal pathogens to oxidants and antimicrobial chemicals. The fungal cell employs conserved eukaryotic signaling pathways and dedicated transcription factors to program its response to these stresses. The oxidant-sensitive transcription factor of yeast, YAP1, and its orthologs in filamentous fungi, are central to tolerance to oxidative stress. The C-terminal domain of YAP1 contains cysteine residues that, under oxidizing conditions, form an intramolecular disulfide bridge locking the molecule in a conformation where the nuclear export sequence is masked. YAP1 accumulates in the nucleus, promoting transcription of genes that provide the cell with the ability to counteract oxidative stress. Chemicals including xenobiotics and plant signals can also promote YAP1 nuclearization in yeast and filamentous fungi. This could happen via direct or indirect oxidative stress, or by a different biochemical pathway. Plant phenolics are known antioxidants, yet they have been shown to elicit cellular responses that would usually be triggered to counter oxidant stress. Here we will discuss the evidence that YAP1 and MAPK pathways respond to phenolic compounds. Following this and other examples, we explore here how oxidative-stress sensing networks of fungi might have evolved to detect chemical stressors. Furthermore, we draw functional parallels between fungal YAP1 and mammalian Keap1-Nrf2 signaling systems. [ABSTRACT FROM AUTHOR]

Background: Alopecia areata (AA) is a noncicatricial alopecia affecting any hair-bearing area. Although AA is considered to be an autoimmune disease, oxidative stress has been shown to be an important factor in the etiology of AA. Trace elements are highly essential for humans since they form the building blocks of large molecules, function as the cofactors of enzymes, and have some key biological functions. The aim of this study was to investigate serum levels of heavy metals like iron (Fe), zinc (Zn), manganese (Mn), copper (Cu), magnesium (Mg), cobalt (Co), cadmium (Cd), and lead (Pb) in patients with AA. Materials and Methods: The study included a patient group of 30 with AA and a control group of 31 healthy individuals. Serum levels of heavy metals were measured using atomic absorption spectrophotometry. Results: The 30 patients included 17 (56.7%) men and 13 (43.3%) women with a mean age of 33.8 (range, 19–48) years. Serum Zn and Mn levels were significantly lower and serum Cd, Fe, Mg, Pb, Co, and Cu levels were significantly higher in the patient group compared to that of the control group (P < 0.05 for all). Conclusion: The results indicated that low levels of Zn and Mn are associated with AA while other metals were normal. So Zn supplementation may have some beneficial effect in AA while Fe prescription is fruitless. [ABSTRACT FROM AUTHOR]

In this study, the potential toxicity of α-Fe2O3-NPs was investigated using a unicellular eukaryote model, Saccharomyces cerevisiae (S. cerevisiae). The results showed that cell viability and proliferation were significantly decreased (p < 0.01) following exposure to 100–600 mg L−1 for 24 h. The IC50 and LC50 values were 352 and 541 mg L−1, respectively. Toxic effects were attributed to α-Fe2O3-NPs rather than iron ions released from the NPs. α-Fe2O3-NPs were accumulated in the vacuole and cytoplasm, and the maximum accumulation (3.95 mg g−1) was reached at 12 h. About 48.6% of cells underwent late apoptosis/necrosis at 600 mg L−1, and the mitochondrial transmembrane potential was significantly decreased (p < 0.01) at 50–600 mg L−1. Biomarkers of oxidative stress [reactive oxygen species (ROS), superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx)] and the expression of apoptosis-related genes (Yca1, Nma111, Nuc1 and SOD) were significantly changed after exposure. These combined results indicated that α-Fe2O3-NPs were rapidly internalized in S. cerevisiae, and the accumulated NPs induced cell apoptosis mediated by mitochondrial impairment and oxidative stress. [ABSTRACT FROM AUTHOR]

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The influence of different concentrations of cadmium (Cd) ions (50 and 100 mg/kg soil) on growth, photosynthetic pigment content, Cd, and iron accumulation in faba bean ( Vicia faba L. cv. Aštar) was studied under laboratory conditions. No significant changes were observed in the growth parameters of shoots (length, fresh, and dry weight). Both tested Cd doses resulted in decrease in root fresh weight by 31.7% and 28.68% and in dry weight by 32.2% and 33.33%, respectively. Increased accumulation of Cd was observed in roots (125- and 173-fold higher than in control) and shoots (125- and 150-fold higher than in control) as a result of applied doses of Cd. Increased accumulation of iron was detected in roots (1.45- and 1.69-fold higher than in control). Decrease in the content of chlorophyll a (by 25.52 and 24.83%, respectively) and chlorophyll b (by 6.90%) after application of Cd 100 as well as decrease in carotenoids (by 40.39 and 38.36%, respectively) was detected. Weak translocation of Cd from roots to shoots pointed to low phytoremediation potential of the tested bean variety in contaminated soil. However, the high tolerance of this cultivar, its relative fast growth, as well as priority of Cd accumulation in roots presume this plant species for phytostabilisation and revegetation of the Cd-contaminated soils. [ABSTRACT FROM AUTHOR]

Background: Poorly soluble cobalt (II, III) oxide particles (Co3O4P) are believed to induce in vitro cytotoxic effects via a Trojan-horse mechanism. Once internalized into lysosomal and acidic intracellular compartments, Co3O4P slowly release a low amount of cobalt ions (Co2+) that impair the viability of in vitro cultures. In this study, we focused on the genotoxic potential of Co3O4P by performing a comprehensive investigation of the DNA damage exerted in BEAS-2B human bronchial epithelial cells. Results: Our results demonstrate that poorly soluble Co3O4P enhanced the formation of micronuclei in binucleated cells. Moreover, by comet assay we showed that Co3O4P induced primary and oxidative DNA damage, and by scoring the formation of γ-H2Ax foci, we demonstrated that Co3O4P also generated double DNA strand breaks. Conclusions: By comparing the effects exerted by poorly soluble Co3O4P with those obtained in the presence of soluble cobalt chloride (CoCl2), we demonstrated that the genotoxic effects of Co3O4P are not simply due to the released Co2+ but are induced by the particles themselves, as genotoxicity is observed at very low Co3O4P concentrations. [ABSTRACT FROM AUTHOR]

The aim of the study was to implicate induction of oxidative stress and antioxidative responses with the effects of cobalt excess on sugarcane plants. Sugarcane (Saccharum officinariumL.) cv. ‘CoS 99225’ grown in refined sand at excess cobalt i.e. 100, 200, 300, 400, and 500 μM. The effect of excess cobalt (>300 μM) was observed on sugarcane as interveinal chlorosis and necrotic spots in middle leaves. Later, affected leaves turned necrotic, dry, and withered. The toxicity of cobalt was also discernible on root weight, cane yield, reduced concentration of sucrose in cane juice, carotenoides, Hill reaction activity, chlorophylls, iron (Fe), relative water content, decreased activity of catalase in leaves, and increase in concentration of lipid peroxidation, phenols, sugars, starch, proline and higher activity of peroxidase, ascorbate peroxidase and superoxide didmutase and accumulation of cobalt in sugarcane leaves. [ABSTRACT FROM PUBLISHER]

While the toxicity of hexavalent chromium is well established, trivalent chromium is an essential nutrient involved in insulin and glucose homeostasis. To study the antioxidant effects of Cr(III)His, cDNA arrays were used to investigate the modulation of gene expression by trivalent chromium histidinate (Cr(III)His) in HaCaT human keratinocytes submitted to hydrogen peroxide (H2O2). Array was composed by a set of 81 expressed sequences tags (ESTs) essentially represented by antioxidant and DNA repair genes. HaCaT were preincubated for 24 h with 50 μM Cr(III)His and were treated with 50 μM H2O2. Total RNAs were isolated immediately or 6 h after the stress. In Cr(III)His preincubated cells, transcripts related to antioxidant family were upregulated (glutathione synthetase, heme oxygenase 2, peroxiredoxin 4). In Cr(III)His preincubated cells and exposed to H2O2, increased expressions of polymerase delta 2 and antioxidant transcripts were observed. Biochemical methods performed in parallel to measure oxidative stress in cells showed that Cr(III)His supplementation before H2O2 stress protected HaCaT from thiol groups decrease and thiobarbituric acid reactive substances increase. In summary, these results give evidence of antioxidant gene expression and antioxidant protection in HaCaT preincubated with Cr(III)His and help to explain the lack of toxicity reported for Cr(III)His. [ABSTRACT FROM AUTHOR]

Hexaammine cobalt (III) chloride is a trivalent complex cation of Co(III) and amine that has previously been shown to act as an inhibitor of insulin secretion, radiosensitizing agent, and an antiviral agent. We have recently reported the anticancer potential of the compound against diethylnitrosamine-induced carcinogenesis in mice. However, there is no report on the potential toxicity of the compound. The present study was conducted to evaluate the tissue distribution of the compound and its potential toxicity following acute administration of the compound through intraperitoneal route in Balb/c mice. Our results showed that cobalt accumulated maximally in kidney, followed by liver, spleen, blood, and lung in a decreasing order and in a dose-dependent manner. Evaluation of liver and kidney function tests revealed that the compound exerted a relatively higher toxicity in kidney, as compared to liver, as evidenced by the sharp enhancement in the serum levels of urea and creatinine in a dose-dependent manner. Examination of levels of lipid peroxidation and selected oxidative stress–related parameters in kidney, liver, and lung suggest that higher accumulation of cobalt in kidney may promote higher oxidative stress in the organ, as compared to liver and lung, which may eventually impair kidney function. [ABSTRACT FROM AUTHOR]

The involvement of nitric oxide (NO) and hydrogen sulfide (H2S) in countermanding heat-inhibited photosynthetic features were studied in wheat (Triticum aestivum L.). Heat stress (HS) was employed at 40 °C after establishment for 6 h daily, and then plants were allowed to recover at 25 °C and grown for 30 days. Glucose (Glc) content increased under HS and repressed plant photosynthetic ability, but the application of sodium nitroprusside (SNP, as NO donor) either alone or with sodium hydrosulfide (NaHS, as H2S donor) reduced Glc-mediated photosynthetic suppression by enhancing ascorbate-glutathione (AsA-GSH) metabolism and antioxidant system, which reduced oxidative stress with decreased H2O2 and TBARS content. Oxidative stress reduction or inhibiting Glc repression was maximum with combined SNP and NaHS treatment, which was substantiated by 2-4-carboxyphenyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (cPTIO) and hypotaurine (HT), scavengers for NO and H2S, respectively. The scavenge of H2S reduced NO-mediated alleviation of HS suggesting of its downstream action in NO-mediated heat-tolerance. However, a simultaneous decrease of both (NO and H2S) led to higher Glc-mediated repression of photosynthesis and oxidative stress in terms of increased H2O2 content that was comparable to HS plants. Thus, NO and H2S cooperate to enhance photosynthesis under HS by reducing H2O2-induced oxidative stress and excess Glc-mediated photosynthetic suppression. [ABSTRACT FROM AUTHOR]

The aim of the present study was to evaluate the basal concentrations of malondialdehyde (MDA) nonenzymatic antioxidants, such as ascorbic acid, α-tocopherol, and retinol in plasma or erythrocytes, and the plasma concentrations of 16 trace minerals in endurance athletes from Extremadura (Spain). In addition, we aimed to assess the possible relationships between some parameters related to cellular oxidative stress with plasma concentrations of some trace minerals. Sixty-two national long-distance men athletes participated in this study. The parameters related to oxidative stress and antioxidant activity were analyzed through high pressure liquid chromatography (HPLC), and trace minerals analysis was performed by inductively coupled plasma mass spectrometry (ICP-MS). We found that plasma MDA was positively correlated with selenium and rubidium. Plasma ascorbic acid was positively correlated with manganese and negatively correlated with cobalt and cadmium. Erythrocyte ascorbic acid was related to arsenic and cesium. Plasma α-tocopherol correlated with copper and manganese negatively and positively with arsenic. Erythrocyte α-tocopherol was positively related to copper, rubidium, and lithium. The findings show that athletes with a high degree of training should monitor their intake and concentrations of α-tocopherol for its fundamental role of neutralizing the excess of reactive oxygen species produced by exercise and the prooxidant effects of several minerals such as arsenic, copper, and lithium. [ABSTRACT FROM AUTHOR]