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Nickel (Ni) is a common metal with a nephrotoxic effect, damaging the kidneys. This study investigated the mechanism by which gallic acid (GA) protects mice kidneys against renal damage induced by Nickel oxide nanoparticles (NiO-NPs). Forty male Swiss albino mice were randomly assigned into four groups, each consisting of ten mice ( n  = 10/group): Group I the control group, received no treatment; Group II, the GA group, was administrated GA at a dosage of 110 mg/kg/day body weight; Group III, the NiO-NPs group, received injection of NiO-NPs at a concentration of 20 mg/kg body weight for 10 consecutive days; Group IV, the GA + NiO-NPs group, underwent treatment with both GA and NiO-NPs. The results showed a significant increase in serum biochemical markers and a reduction in antioxidant activities. Moreover, levels of 8-hydroxy-2'-deoxyguanosine (8-OH-dG), phosphorylated nuclear factor kappa B (p65), and protein carbonyl (PC) were significantly elevated in group III compared with group I. Furthermore, the western blot analysis revealed significant high NF-κB p65 expression, immunohistochemistry of the NF-κB and caspase-1 expression levels were significantly increased in group III compared to group I. Additionally, the histopathological inspection of the kidney in group III exhibited a substantial increase in extensive necrosis features compared with group I. In contrast, the concomitant coadministration of GA and NiO-NPs in group IV showed significant biochemical, antioxidant activities, immunohistochemical and histopathological improvements compared with group III. Gallic acid has a protective role against kidney dysfunction and renal damage in Ni-nanoparticle toxicity.

Nickel phytotoxicity has been attributed, among others, to oxidative stress. However, little is known about Ni-induced phospholipid modifications, including the oxidative ones. Accumulation of reactive oxygen species (ROS), antioxidative enzyme activities, malondialdehyde and the early lipid oxidation products contents, membrane permeability, phospholipid profile as well as phospholipid unsaturation degree were studied in the 1st and the 2nd leaves of hydroponically grown cucumber seedlings subjected to Ni stress. Compared to the 2nd leaf the 1st one showed stronger visual Ni toxicity symptoms, higher Ni, O 2 .- and H 2 O 2 accumulation as well as greater enhancement in membrane permeability. Enzyme activities were differently influenced by Ni stress, however most pronounced changes were generally found in the 1st leaf. Ni treatment resulted in oxidation of leaf lipids, which was evidenced by appearance of increased contents of MDA and the early produced oxylipins. Among the latter 9-hydroxyoctadecatrienoic acid (9-HOTrE) and 13-hydroxyoctadecatrienoic acid (13-HOTrE) contents showed the most pronounced increase in response to Ni treatment. Exposure to the metal led to the changes in the leaf phospholipid profile and increased degree of phospholipid unsaturation. The obtained results have been discussed in relation to the difference in Ni stress severity between the 1st and the 2nd leaves., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Although the production and use of nickel oxide nanoparticles (NiONP) are widespread, environmental and public health problems are associated with it. The kidney is the primary organ in excretion and is among the target organs in nanoparticle toxicity. This study aimed to compare the renal toxicity of nickel oxide (NiO) microparticles and nickel oxide nanoparticles by different routes of administration, such as oral, intraperitoneal (IP), and intravenous (IV). Seven groups were formed, with 42 male rats and six animals in each group. NiO oral (150 mg/kg), NiO IP (20 mg/kg), NiO IV (1 mg/kg), NiONP oral (150 mg/kg), NiONP IP (20 mg/kg), and NiONP IV (1 mg/kg) was administered for 21 days. After NiO and NiONP administration, a decrease in antioxidant activities and an increase in lipid peroxidation occurred in the kidney tissue of rats. Increased kidney urea, uric acid, and creatinine levels were observed. Inhibition of acetylcholinesterase activity and an increase in interleukin 1 beta were detected. Apoptotic markers, Bax, caspase-3, and p53 up-regulation and Bcl-2 down-regulation were observed. In addition, histopathological changes occurred in the kidney tissue. In general, it was observed that nickel oxide microparticles and nickel oxide nanoparticles cause inflammation by causing oxidative stress in the kidney tissue, and NiONP IV administration is more effective in renal toxicity., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Many studies have focused on the neurotoxic effects of single metals, while investigation on the exposure to metal mixtures, which mainly occur in real-life situations, is scarce. This study sought to assess the neurotoxic effect of Ni, Co, and Pb binary mixtures and their individual effects in hippocampal neuronal cells (HT-22). Cells were exposed to Ni, Co, and Pb separately for 48 h at 37°C and 5% CO 2 , and cell viability was assessed. Morphological assessment of the cells exposed to binary mixtures of Co, Ni, and Pb and single metals was assessed using a microscope. Furthermore, acetylcholinesterase (AChE) activity, oxidative stress biomarkers (glutathione [GSH] and malondialdehyde [MDA] levels, catalase [CAT], and glutathione-S transferase [GST] activities) and nitric oxide [NO] levels were evaluated after treatment with the binary mixtures and single metals. Binary mixtures of the metals reduced cell viability, exerting an additivity action. The combinations also exerted synergistic action, as revealed by the combination index. Furthermore, a significant reduction in AChE activity, GSH levels, CAT and GST activities, and high MDA and NO levels were observed in neuronal cells. The additive interactions and synergistic actions of the binary mixtures might contribute to the significant reduction of AChE activity, GSH levels, GST, and CAT activities, and an increase in MDA and NO levels. The findings from this study revealed significant evidence that binary mixtures of Co, Pb, and Ni may induce impaired neuronal function and, ultimately, neurodegeneration., (© 2024 The Author(s). Environmental Toxicology published by Wiley Periodicals LLC.)

Nickel (Ni) is recognized as a carcinogenic metal, and its widespread use has led to severe environmental and health problems. Although the lung is among the main organs affected by Ni, the precise mechanisms behind this effect remain poorly understood. This study aimed to elucidate the physiological mechanisms underlying Ni-induced pulmonary fibrosis (PF), using various techniques including histopathological detection, biochemical analysis, immunohistochemistry, western blotting, and quantitative real-time PCR. Mice were treated with nickel chloride (NiCl 2 ), which induced PF (detected by Masson staining), up-regulation of α-smooth muscle actin (α-SMA), and collagen-1 mRNA and protein expression. NiCl 2 was found to induce PF by: activation of the epithelial-mesenchymal transition (EMT) and the transforming growth factor-β1 (TGF-β1)/Smad signaling pathway; up-regulation of protein and mRNA expression of TGF-β1, p-Smad2, p-Smad3, vimentin, and N-cadherin; and down-regulation of protein and mRNA expression of E-cadherin. In addition, NiCl 2 treatment increased malondialdehyde content while inhibiting antioxidant activity, as indicated by decreased catalase, total antioxidant capacity, and superoxide dismutase activities, and glutathione content. Co-treatment with the effective antioxidant and free radical scavenger N-acetyl cysteine (NAC) plus NiCl 2 was used to study the effects of oxidative stress in NiCl 2 -induced PF. The addition of NAC significantly mitigated NiCl 2 -induced PF, and reversed activation of the TGF-β1/Smad signaling pathway and EMT. NiCl 2 -induced PF was therefore shown to be due to EMT activation via the TGF-β1/Smad signaling pathway, mediated by oxidative stress., (© 2024 Wiley Periodicals LLC.)

The new technological applications of nickel (Ni) raise concerns over its harmful effects on the environment and human health. Pomiferin isolated from Osage orange is evaluated in in vitro and in vivo laboratory bioassays. This study focused the effects of pomiferin on Ni-caused hepatic injury and its underlying mechanisms. With this aim, Sprague-Dawley rats received 10 mg/kg nickel chloride (NiCl 2 ) for 7 d by intraperitoneal injections. Pomiferin was given orally once a day at different doses (75, 150, and 300 mg/kg) for 20 d after exposure to NiCl 2 . Animals were anesthetized and livers were carefully collected to evaluate oxidative stress, inflammation, vascular injury, and hepatic function. Also, immunofluorescence analysis of apoptosis and DNA damage was performed on rat hepatic tissues. NiCl 2 increased MDA production while reducing SOD, CAT, and GPx activity. NiCl 2 induced the production of inflammatory cytokines and also platelet activation in hepatic tissue. Moreover, there were significant increases in AST, ALT, and LDH levels. NiCl 2 also caused significant pathological changes in hepatic. Additionally, it remarkably induced up-regulations of apoptotic marker and 8-OHdG expressions by immunofluorescence labeling in liver cells. Whereas, pomiferin significantly attenuated lipid peroxidation and increased antioxidant defense system in liver. Also, the use of pomiferin prevented deregulated inflammatory process by signaling pathways nuclear factor kappa B (NFκB)/COX-2/TNF-α/IL-1β/IL-6. In addition, pomiferin diminished histopathologic evidence of hepatic toxicity and significantly lower expressions of caspase 3 and 8-OHdG were observed in liver cells. Pomiferin seems to counteract the deleterious effects of NiCl 2 on hepatic tissue through different cellular and signaling mechanisms.

The two trace elements cobalt (Co) and nickel (Ni) are widely distributed in the environment due to the increasing industrial application, for example in lithium-ion batteries. Both metals are known to cause detrimental health impacts to humans when overexposed and both are supposed to be a risk factor for various diseases. The individual toxicity of Co and Ni has been partially investigated, however the underlying mechanisms, as well as the interactions of both remain unknown. In this study, we focused on the treatment of liver carcinoma (HepG2) and astrocytoma (CCF-STTG1) cells as a model for the target sites of these two metals. We investigated their effects in single and combined exposure on cell survival, cell death mechanisms, bioavailability, and the induction of oxidative stress. The combination of CoCl 2 and NiCl 2 resulted in higher Co levels with subsequent decreased amount of Ni compared to the individual treatment. Only CoCl 2 and the combination of both metals led to RONS induction and increased GSSG formation, while apoptosis and necrosis seem to be involved in the cell death mechanisms of both CoCl 2 and NiCl 2 . Collectively, this study demonstrates cell-type specific toxicity, with HepG2 representing the more sensitive cell line. Importantly, combined exposure to CoCl 2 and NiCl 2 is more toxic than single exposure, which may originate partly from the respective cellular Co and Ni content. Our data imply that the major mechanism of joint toxicity is associated with oxidative stress. More studies are needed to assess toxicity after combined exposure to elements such as Co and Ni to advance an improved hazard prediction for less artificial and more real-life exposure scenarios., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The co-occurrence of heavy metals and microplastics (MPs) is an emerging issue that has attracted considerable attention. However, the interaction of nickel oxide nanoparticle (nano-NiO) combined with MPs in soil was poorly researched. Here, experiments were conducted to study the influence of nano-NiO (200 mg/kg) and polyethylene (PE) MPs with different concentrations (0.1, 1, and 10%) and sizes (13, 50, and 500 µm) on earthworms for 28 days. Compared to control, the damage was induced by PE and nano-NiO, which was evaluated by biomarker Integrated Biomarker Response index: version 2 (IBRv2) based on six biomarkers including SOD, POD, CAT, MDA, AChE, Na + /K + -ATPase and cellulase. The majority of the chosen biomarkers showed significant but complicated responses with increasing contaminant concentrations after 28 days of exposure. Moreover, the joint effect was assessed as antagonism by the effect addition index (EAI). Overall, this work expands our understanding of the combined toxicity of PE and nano-NiO in soil ecosystems., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Nickel is a heavy metal that is regarded as a possible hazard to living organisms due to its toxicity and carcinogenicity. Nickel chloride (NiCl 2 ), an inorganic divalent Ni compound, has been shown to cause oxidative stress in cells by altering the redox equilibrium. We have investigated the effect of NiCl 2 on isolated human erythrocytes under in vitro condition., Methods: Isolated erythrocytes were treated with different concentrations of NiCl 2 (25-500 µM) for 24 h at 37 ºC. Hemolysates were prepared and several biochemical parameters were analyzed in them., Results: Treatment of erythrocytes with NiCl 2 enhanced the intracellular generation of reactive oxygen species (ROS). A significant increase in hydrogen peroxide levels and oxidation of proteins and lipids was also seen. This was accompanied by a reduction in levels of nitric oxide, glutathione, free amino groups and total sulfhydryl groups. NiCl 2 treatment impaired both enzymatic and non-enzymatic defense systems, resulting in lowered antioxidant capacity and diminished ability of cells to quench free radicals and reduce metal ions. NiCl 2 exposure also had an inhibitory effect on the activity of enzymes involved in pathways of glucose metabolism (glycolytic and pentose phosphate shunt pathways). Increased level of methemoglobin, which is inactive in oxygen transport, was also seen. The rate of heme breakdown increased resulting in the release of free iron. Exposure to NiCl 2 led to considerable cell lysis, indicating damage to the erythrocyte membrane. This was supported by the inhibition of membrane bound enzymes and increase in the osmotic fragility of NiCl 2 treated cells. NiCl 2 treatment caused severe morphological alterations with the conversion of normal discocytes to echinocytes. All changes were seen in a NiCl 2 concentration-dependent manner., Conclusion: NiCl 2 generates cytotoxic ROS in human erythrocytes which cause oxidative damage that can decrease the oxygen carrying capacity of blood and also lead to anemia., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. The authors declare that there is no conflict of interest., (Copyright © 2023 Elsevier GmbH. All rights reserved.)

Thioredoxin reductase 3 (Txnrd3) plays a crucial role in antioxidant and anti-cancer activities, and sperm maturation. The damage of heavy metals, including Nickel (Ni), is the most prominent harm in social development, and hampering Txnrd3 might exacerbate Ni-induced cardiac damage. In this study, a total of 160 8-week-old C57BL/N male mice with 25-30 g weight of Txnrd3+/+ wild-type and Txnrd3-/- homozygote-type were randomly divided into eight groups. The mice in the control and Ni groups were gavaged with distilled water and a freshly prepared 10 mg/kg NiCl 2 solution. Melatonin (Mel) groups were administered at a concentration of 2 mg/kg for 21 days at the mice's 0.1 ml/10 g body weight. Ni exposure up-regulated the messenger RNA (mRNA) levels of mitochondrial apoptosis (caspase-3, caspase-9, cytochrome c, p53, and BAX), autophagy (LC3, ATG 1, ATG 7, and Beclin-1), and inflammation (TNF-α, COX 2, IL-1β, IL-2, IL-6, and IL-7)-related markers, but down-regulated the mRNA levels of BCL-2, p62 and mTOR (p < .05). Ni exposure decreased the expression of BCL-2 and p62 protein but increased the expression levels of caspase-3, caspase-9, cytochrome c, p53, BAX, ATG 7, Beclin-1, TNF-α, COX 2, IL-1β and IL-2 protein (p < .05). Ni increased the contents of glutathione disulfide (GSSG) and malondialdehyde (MDA) and decreased the activities of catalase (CAT) and total superoxide dismutase (T-SOD) (p < .05). Decreased Txnrd3 expression significantly exacerbated changes compared to the Ni exposure (p < .05). Mel significantly attenuated these changes, but the effect decreased when Txnrd3 was inhibited (p < .05). In conclusion, decreased Txnrd3 expression promoted Ni-induced mitochondrial apoptosis and inflammation via oxidative stress and aggravated heart damage in mice. Decreased Txnrd3 expression significantly reduced the protective effect of Mel to Ni exposure., (© 2022 Wiley Periodicals LLC.)

Nickel nanoparticles (Ni-NPs) are widely used for multiple purposes in industries. Ni-NPs exposure is detrimental to ecosystems owing to widespread use, and so their toxicity is important to consider for real-world applications. This review mainly focuses on the notable pathophysiological activities of Ni-NPs in various research models. Ni-NPs are stated to be more toxic than bulk forms because of their larger surface area to volume ratio and are reported to provoke toxicity through reactive oxygen species generation, which leads to the upregulation of nuclear factor-κB and promotes further signaling cascades. Ni-NPs may contribute to provoking oxidative stress and apoptosis. Hypoxia-inducible factor 1α and mitogen-activated protein kinases pathways are involved in Ni-NPs associated toxicity. Ni-NPs trigger the transcription factors p-p38, p-JNK, p-ERK1/2, interleukin (IL)-3, TNF-α, IL-13, Fas, Cyt c, Bax, Bid protein, caspase-3, caspase-8, and caspase-9. Moreover, Ni-NPs have an occupational vulnerability and were reported to induce lung-related disorders owing to inhalation. Ni-NPs may cause serious effects on reproduction as Ni-NPs induced deleterious effects on reproductive cells (sperm and eggs) in animal models and provoked hormonal alteration. However, recent studies have provided limited knowledge regarding the important checkpoints of signaling pathways and less focused on the toxic limitation of Ni-NPs in humans, which therefore needs to be further investigated.

The present study focused on affective and cognitive behaviors in male Wistar rats, following direct and unique exposure to nickel chloride (NiCl 2 ), as well as the possible involvement of oxidative stress. The rats were exposed to NiCl 2 (300 μM), by intracerebral administration of 2 μL of this metal at the right hippocampus, using the stereotaxic approach. Five days after the surgery, a battery of behavioral tests was performed, including the open-field test (OFT) and elevated plus maze test (EPM) to assess the state of anxiety-like behavior and forced swimming test (FST) for depressive-like behavior. Y-maze and Morris Water Maze (MWM) were used to evaluate working memory and spatial learning. Thereafter, oxidative stress markers of the hippocampus were evaluated. The results confirm that NiCl 2 exerts anxiogenic effects in both anxiety tests and depressogenic effects in the FST. In addition, MWM and Y-maze data show that NiCl 2 causes memory and spatial learning disorders. The biochemical assay results showed that intrahippocampal injection of NiCl 2 increased the levels of nitric oxide and lipid peroxidation (p < 0.001), while the activities of catalase and superoxide dismutase were significantly decreased in the hippocampus (p < 0.01). Overall, these results suggest that NiCl 2 causes affective and cognitive disorders and oxidative stress in rats.

Introduction: This study was designed to report the biological effect of nickel oxide nanoparticles (NiO NPs) in albino mice., Material and Methods: Five weeks old albino mice of both sex were intraperitoneally injected either with 20 mg (low dose) or 50 mg/mL saline/kg body weight (high dose) of NiO NPs for 14 days. Saline-treated controls were maintained in parallel. Complete blood count, selected serum biochemical parameters and oxidative stress biomarkers from vital organs were determined in all subjects., Results: Male mice treated with NiO NPS had increased blood urea nitrogen, elevated superoxide dismutase (SOD) in liver elevated MDA in liver, kidney and heart and reduced catalase activity in heart and kidney. Female mice treated with NiO NPs had significantly reduced serum albumin and total proteins, SOD in lungs and elevated MDA in liver., Discussion: We are reporting that intraperitoneal injections of NiO NPs for 14 days drastically affect blood serum parameters and oxidative stress biomarkers from vital organs of albino mice., Conclusion: Toxic effects of NiO NPs were dose and sex dependent and they were more pronounced at higher dose and in male mice.

The employ of nanomaterials (NMs) has exponentially grown due to the large number of technological advances in industrial, pharmaceutical and medical areas. That is the case of alumina (Al) nanoparticles which are extensively employed as support in heterogeneous catalysis processes. However, these NMs can cause great toxicity because of their ubiquitous properties, such as extremely small size and high specific surface area. So, it is required to assess the potential deleterious effects of these NMs on living organisms. In the present study, we analyze the oxidative stress and genotoxic potential of a nanoceramic catalyst Ni/-Al 2 O 3 (NC) and the NMs involved in their synthesis, -Al 2 O 3 support (SPC) and NiO/-Al 2 O 3 precursor (PC) on Rhinella arenarum larvae. Biomarkers of oxidative stress and genotoxic damage were measured in tadpoles exposed to 5 and 25 mg/L of each NMs for 96 h. The results indicated an inhibition of catalase activity in tadpoles exposed to both concentrations of PC and to 25 mg/L of SPC and NC. Moreover, both exposure concentrations of PC and NC significantly inhibited superoxide dismutase activity. Exposure to the three NMs caused inhibition of glutathione S-transferase activity, but there were no significant variations in reduced glutathione levels. Oxidative stress damage (lipid peroxidation) was observed in tadpoles treated with 25 mg/L PC, while the other treatments did not produce alterations. The MNs frequency significantly increased in larvae exposed to 25 mg/L PC indicating irreversible genotoxic damage. The results show that these NMs exert genotoxic effects and antioxidant defense system disruption in R. arenarum larvae., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Anthropogenic activity has increased human exposure to metals and resulted in metal induced toxicity. Essential trace elements like cobalt (Co), nickel (Ni), and manganese (Mn) are best known for their roles as important cofactors in many enzymes involved in signalling, metabolism, and response to oxidative stress. However, deficiencies as well as long-term overexposure to these metals can result in negative health effects. Co has been associated with cardiomyopathy, lung disease, and hearing damage, while Ni is a known carcinogen, as well as a common sensitizing metal. Mn is best classified as a neurotoxicant that causes a disorder alike to idiopathic Parkinson's disease known as Manganism. Although the mechanisms of Co, Ni, and Mn toxicity are complex and have yet to be fully elucidated, research over the years has provided useful insights into understanding metal-induced detrimental effects at the cellular and molecular level. One area of research that has been explored in less detail are metal interactions with lipids and biological membranes, which are a potentially critical target as membranes are the first point of contact for cells. This review covers the current understandings of Co, Ni and Mn toxicity, in terms of human exposure, homeostasis and mechanisms of transport, potential cellular targets, and, of primary focus, metal interactions with lipid and biomembranes. A variety of effects like membrane rigidification, leakage affecting membrane potentials, lipid phase changes, alterations in lipid metabolism and changes of cellular morphology illustrate the vast potential for metal-based membrane effects contributing to their toxicity., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

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.)

Background: Nickel activates the signaling pathways through the oxygen sensing mechanism and the signaling cascades that control hypoxia-inducible transcriptional gene expressions through oxidative stress. This review emphasizes on the recent updates of nickel toxicities on oxidant and antioxidant balance, molecular interaction of nickel and its signal transduction through low oxygen microenvironment in the in-vivo physiological system., Discussion: Nickel alters intracellular chemical microenvironment by increasing ionized calcium concentration, lipid peroxidation, cyclooxygenase, constitutive nitric oxide synthase, leukotriene B4, prostaglandin E2, interleukins, tumor necrosis factor-α, caspases, complement activation, heat shock protein 70 kDa and hypoxia-inducible factor-1α. The oxidative stress induced by nickel is responsible for the progression of metastasis. It has been observed that nickel exposure induces the generation of reactive oxygen species which leads to the increased expression of p53, NF-kβ, AP-1, and MAPK. Ascorbic acid (vitamin C) prevents lipid peroxidation, oxidation of low-density lipoproteins and advanced oxidation protein products. The mechanism involves that vitamin C is capable of reducing ferric iron to ferrous iron in the duodenum, thus the availability of divalent ferrous ion increases which competes with nickel (a divalent cation itself) and reduces its intestinal absorption and nickel toxicities., Conclusion: Reports suggested the capability of ascorbic acid as a regulatory factor to influence gene expression, apoptosis and other cellular functions of the living system exposed to heavy metals, including nickel., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

The aim was to explore the biological effect of nickel (Ni) and titanium (Ti) ions released from dental alloys. NiTi alloy were exposed to 40 mL of artificial saliva (pH = 4.8, t = 37 °C). The dynamics of Ni and Ti ions release during corrosion were recorded on the 3th, 7th and 14th day. Biological effect of Ni and Ti ions released from alloy was explored on cell lines of human tongue CAL 27, liver Hep G2 and colon Caco-2. Neutral Red uptake assay for the estimation of cell viability/cytotoxicity and 2',7'-dichlorofluorescein diacetate fluorimetric assay for reactive oxygen species were used. Cells were exposed to the following concentration of corrosion products: 5.0×, 1.0×, 0.5 and 0.1× during the period of 24, 48 and 72 h. To check the effect of each metal separately, cells were exposed to nickel-chloride and titanium-dioxide of corresponding concentration. The release of Ni is higher than of Ti (15.1-30.4 μg/L for Ni and 9.0-17.3 μg/L for Ti, respectively) and 5× higher concentrations are needed to induce cytotoxic effect. Ni and Ti ions alone do not induce a major cytotoxic effect, but their combination does indicating their synergistic effect. Increase in concentration of Ni and Ti tends to increase cytotoxicity, Ti more than Ni. Cytotoxicity and induction of free radicals are in strong positive linear correlation. Ions released from NiTi alloy during 14 days do not induce significant cytotoxic effect and would not have a clinically important impact. Cytotoxic effect is largely the result of the induction of free radicals., (Copyright © 2019 Elsevier Inc. All rights reserved.)

The present study identified inverse relationships between nickel (Ni) levels and growth, photosynthesis and physio-biochemical attributes, but increasing levels of Ni stress enhanced methylglyoxal, electrolyte leakage, hydrogen peroxide, and lipid peroxidation content. Exogenous application of salicylic acid (SA) (10 -5  M) ameliorated the ill-effects of Ni by restoring growth, photosynthesis and physio-biochemical attributes and increasing the activities of enzymes associated with antioxidant systems, especially the ascorbate-glutathione (AsA-GSH) cycle and glyoxalase system. In addition, SA application to Ni-stressed plants had an additive effect on the activities of the ascorbate and glutathione pools, and the AsA-GSH cycle enzymes (ascorbate peroxidase, monodehydroascorbate reductase, dehydroascorbate reductase, glutathione reductase), superoxide dismutase, catalase, glutathione S-transferase, and osmolyte biosynthesis). This trend also follows in glyoxalase system viz. glyoxalase I and glyoxalase II enzymes. Nevertheless, exogenous SA supplementation restored mineral nutrient contents. Principal component analysis showed that growth, photosynthesis, and mineral nutrient parameters were positively correlated with each other and negatively correlated with antioxidant enzymes and oxidative stress biomarkers. Hence, SA is an alternative compound with potential application in the phytoremediation of Ni., (Copyright © 2019 Elsevier Inc. All rights reserved.)

The aim of this study was to compare the ecotoxicity of nickel (Ni) and zinc (Zn) assayed as single and as binary mixture. In addition, how were affected the population growth rates and oxidative stress biomarkers, comparing single to binary exposures. The toxicity tests were performed on Lemna gibba using a 7-day test. All calculations were made using measured total dissolved metal concentrations. IC50-7d, based on growth rate calculated on frond number and fresh weight, were 2.47/3.89 mg/L, and 76.73/76.93 mg/L, for Ni and Zn, respectively. Single metals affected plant growth following a non-linear concentration-response relationship. LOEC values for each metal were obtained at 0.92 and 20.1 mg/L for Ni and Zn, respectively. Biomarkers of the antioxidant response like Catalase (CAT; EC 1.11.1.6), ascorbate peroxidase (APOX; EC 1.11.1.11) and guaiacol peroxidase (GPOX; EC 1.11.1.7) activities in single metals assays were higher than controls, but when similar concentrations were added as mixtures, that increase was reduced and inhibition with respect to the control was observed for GPOX. APOX showed the highest activity. The concentration addition (CA) approach was evaluated and resulted in a correct predictor of Ni-Zn mixture toxicity on Lemna gibba. This was made comparing the EC50 and LOEC, measured taking the growth rate as endpoint, with those expected values according to the CA model. However, the measured biomarkers indicating a positive response to free radicals did not fit to concentration addition model when assayed in the binary mixture. Also, the main activity response of these was observed within a range of concentrations below the LOEC values for the mixture.

Despite the increasing use of nickel oxide (NiO) nanoparticles (NPs), limited information is available on their toxicological effects. Health consequences of 28 days repeated oral exposure to NiO NPs have not been explored thoroughly. Hence, toxicity investigations were performed after 28-day daily exposure in albino Wistar rats with NiO NPs following Organization for Economic Co-operation and Development test guideline 407. Histopathology, biochemical indices including oxidative stress and biodistribution patterns were evaluated to decipher the toxicological impact of NiO NPs. NiO NP characterization by transmission electron microscopy showed an average size of 12.9 (±3.4) nm. Histological studies depicted a prominent impact on the vital organs of the rats. A dose-dependent rise in both aminotransferase enzyme values was recorded in the homogenates of liver and kidney tissues. A significant decrease in superoxide dismutase activity and increase in catalase activity was noted. Further, a dose-dependent decrease in reduced glutathione content was recorded in rats, which suggested generation of reactive oxygen species and oxidative stress. Increase in the malondialdehyde levels was observed with an increase in the dose substantiating the antioxidant enzyme activity profiles. Biodistribution studies indicated maximum accumulation of Ni content in liver followed by kidney. Excretion of Ni was predominantly through feces and a little through renal clearance. Our study indicated that NiO NPs adversely alter the biochemical profile of the rats and cause histological damage. Further investigations are warranted to address the mechanism by which physiological path these NiO NPs exhibit their toxic nature in in vivo., (© 2019 John Wiley & Sons, Ltd.)

Nickel is a ubiquitous heavy-metal pollutant in lakes and severely affects aquatic organisms. Aquatic plants are often initially linked to having heavy metal contents and further are proposed as phytoremediation agent to remove heavy metal from water. Although the toxic effects of nickel on aquatic plants are thoroughly explored, the effective investigation to increase Ni tolerance is still in its infancy. The role of rare-earth elements (REEs) in plant resisting heavy-metal pollution has recently received considerable interest. To explore the physiological effects of REEs on Potamogeton crispus under Ni stress, we explored whether or not the additive exposure to low-dose yttrium (Y; 2.5 μM) promotes the polyamine metabolism, antioxidation, and photosynthesis performance of P. crispus under Ni stress values of 0, 50, 100, 150, and 200 μM. Results showed that Y exposure did not influence Ni bioaccumulation in P. crispus. Furthermore, Y exposure alleviated the adverse effects of Ni stress to convergent degrees because Y positively converts putrescine into spermidine and spermine, inhibits oxidative stress, increases the total chlorophyll content, and maximum/potential quantum efficiency of photosystem II. We concluded that low-dose Y can positively regulate polyamine transformation, inhibit oxidative stress, stimulate photosynthesis, and finally promote the resist ability of P. crispus to nickel stress. Thus, REEs have potential to be applied in regulating submerged plant tolerance to aquatic heavy-metal pollution., (Copyright © 2019. Published by Elsevier Ltd.)

In recent years, release of chemical pollutants has increased due to anthropogenic activities. Heterocystous filamentous cyanobacteria constitute dominant paddy microflora and are excellent biofertilizers augmenting rice productivity. Cyanobacteria are frequently exposed to toxic metals, nickel and arsenic are one of the major toxicants present. We exposed two species of diazotrophic cyanobacteria Anabaena sp. PCC 7120 and Anabaena doliolum, to sub-lethal concentrations (15.0 and 9.0 μM) of Ni 2+ and (17.0 and 11 mM) of arsenite (AsIII) and analyzed at different days of treatments (0, 1, 7, and 15 days) for oxidative damage and antioxidative biomarkers. Lipid peroxidation was enhanced (1.5- to 2.5-fold increase in MDA content), indicating damaging effects of Ni 2+ and As(III) on membrane. Although Ni 2+ and As(III), both induced oxidative stress in both species, Anabaena PCC 7120 experienced less stress than A. doliolum. This could be explained by a higher activity of antioxidant enzymes catalase (CAT), ascorbate peroxidase (APX), glutathione reductase (GR) in Anabaena PCC 7120 (4.6-, 2.0- and 1.4-fold [Ni 2+ ] 3.2-, 2.5-, and 2.08-fold [As]) compared to A. doliolum (4.2-, 2.5-, and 1.3-fold [Ni 2+ ] and 3.2-, 3.33-, and 1.8-fold [As]). Moreover, superoxide dismutase registered less inhibition in Anabaena sp. PCC 7120 (1.5 and 1.8) compared to A. doliolum (1.8 and 2.3) under Ni 2+ and As(III) stress. In addition to, IBR revealed that As(III) imposes severe impact on both strain, however, A. doliolum suffers most. Therefore, the study demonstrates interspecies variation in survival strategy of two Anabaena species and difference in potential of two different toxicants to produce oxidative stress., (© 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

High aspect ratio nanomaterials (NM) have a promising future in medicine and industry as a unique category of NM. Consequently, it is important to evaluate their potential biological side-effects before crediting their use. To understand the mechanisms of degradation, internalisation, and interaction with different biological targets, we used the in vivo model Drosophila melanogaster to obtain a systematic and complete study on high aspect ratio Ni nanowires (NiNW), compared with low aspect ratio Ni nanospheres (NiNS), and NiSO 4 as a model of agent releasing nickel ions. The distinguished shape of nanowires showed changes in their characteristics after oral administration until they reached the intestinal lumen, where their diameter decreased significantly. For the first time, we confirmed the internalization of needle-shaped materials via perforation of the intestinal barrier. Moreover, the results showed that D. melanogaster is a valid and effective tool in studies related to magnetic resonance imaging (MRI). Additionally, NiNM induced DNA damage and molecular changes at the gene expression level, in association with increase in oxidative stress levels. Notably, the observed negative effects were related to nickel as a metal rather than to its shape, since the effects induced by the three Ni forms were notably similar. In addition, independent of their form, Ni compounds did not induce toxic or mutagenic impacts. Our Drosophila model can be used to understand different phenomena related to high aspect ratio NM exposure, such as degradation, internalization and interaction with different targets.

Exposure to heavy metal-containing dust arising from stone quarrying may cause severe health problems. The aim of this study was to evaluate the impact of stone quarrying in Riyadh (Saudi Arabia) on the Libyan jird Meriones libycus. Soil samples and jirds were collected from four sites located at different distances from the quarrying area. Soil from the first (500 m away from the quarry) and second (1800 m away) sites showed a significant increase in cadmium (Cd), lead (Pb), nickel (Ni), and vanadium (V) when compared with the reference site (38,000 m away). Jirds at these sites exhibited significant increases in liver, kidney, lung, and fur levels of Cd, Pb, Ni, and V. Serum transaminases, creatinine, and malondialdehyde (MDA) levels were significantly increased in jirds, whereas reduced glutathione (GSH) levels decreased. Liver, kidney, and lung tissues of jirds, collected from the first and second sites, showed significantly increased MDA and decreased GSH levels. Additionally, animals at both sites showed altered hematological parameters and several histopathological changes in their liver, kidney, and lung. Soil and animals at the third site (7300 m away) showed no significant changes. Thus, our study showed the impact and hazardous effects of quarrying on the liver, kidney, lung, and hemogram of M. libycus. These findings can provide scientific evaluation for studying the impact of quarrying on the workers and communities living close to the studied area.

The present work aimed to elucidate whether the toxic effects of nickel oxide (NiO) nanoparticles (NPs) on the yeast Saccharomyces cerevisiae were associated with oxidative stress (OS) and what mechanisms may have contributed to this OS. Cells exposed to NiO NPs accumulated superoxide anions and hydrogen peroxide, which were intracellularly generated. Yeast cells coexposed to NiO NPs and antioxidants (l-ascorbic acid and N- tert-butyl-α-phenylnitrone) showed quenching of reactive oxygen species (ROS) and increased resistance to NiO NPs, indicating that the loss of cell viability was associated with ROS accumulation. Mutants lacking mitochondrial DNA (ρ 0 ) displayed reduced levels of ROS and increased resistance to NiO NPs, which suggested the involvement of the mitochondrial respiratory chain in ROS production. Yeast cells exposed to NiO NPs presented decreased levels of reduced glutathione (GSH). Mutants deficient in GSH1 ( gsh1Δ) or GSH2 ( gsh2Δ) genes displayed increased levels of ROS and increased sensitivity to NiO NPs, which underline the central role of GSH against NiO NPs-induced OS. This work suggests that the increased levels of intracellular ROS (probably due to the perturbation of the electron transfer chain in mitochondria) combined with the depletion of GSH pool constitute important mechanisms of NiO NPs-induced loss of cell viability in the yeast S. cerevisiae.

This work was designed to assess the potential role of silicon dioxide nanomaterial (nano-SiO 2 ) in enhancing barley's tolerance to nickel oxide nanomaterial (nano-NiO). For this purpose, plants were grown for 14days under nano-NiO (120mgkg -1 ) single and co-exposure with nano-SiO 2 (3mgkg -1 ). The exposure of barley to nano-NiO caused a significant decrease in growth-related parameters and induced a negative response on the photosynthetic apparatus. However, upon nano-SiO 2 co-exposure, the inhibitory effects of nano-NiO were partially reduced, with lower reductions in fresh and dry biomass, and with the recovery of the photosynthesis-related parameters. Plants growing under nano-NiO stress showed an overproduction of superoxide anion (O 2 ), which favored the occurrence of oxidative stress and the enhancement of lipid peroxidation (LP), but the co-treatment with nano-SiO .- ), which favored the occurrence of oxidative stress and the enhancement of lipid peroxidation (LP), but the co-treatment with nano-SiO 2 reverted this tendency, generally lowering or maintaining the levels of LP and stimulating the redox pathway of thiols. The evaluation of the antioxidant (AOX) system revealed that nano-NiO induced the accumulation of proline, along with a decrease in ascorbate in leaves. Furthermore, superoxide dismutase (SOD) activity was significantly enhanced and catalase (CAT) and ascorbate peroxidase (APX) seemed to have a pivotal role in H 2 O 2 detoxification in leaves and roots, respectively. The response of the AOX system was even more prominent upon nano-SiO 2 in barley plants under nano-NiO stress, possibly due to the Si-mediated protection against oxidative stress, by a more proactive performance of the plant AOX system.2 in barley plants under nano-NiO stress, possibly due to the Si-mediated protection against oxidative stress, by a more proactive performance of the plant AOX system., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Objective: To study the protective effect of Ascorbic acid (AA) on the injury of nickel-exposed mouse embryonic fibroblasts (NIH/3T3) . Methods: A model of damage induced by 50 μg/mL nickel refining dust was established to determine the relative survival rate of cells, superoxide dismutase (SOD) , lactate dehydrogenase (LDH) and glutathione peroxidase. (GSH-Px) activity, hydrogen peroxide (H(2)O(2)) and malondialdehyde (MDA) content, and p53 (wild-type) , Bcl-2 protein expression. To investigate the protective effect of different doses of ascorbic acid (25, 50, 100 mmol/L) on nickel-refined dust-induced NIH/3T3 cell injury. Results: The study showed that ascorbic acid Ⅲ group can make the NIH/3T3 cell survival rate increased significantly; Apoptosis rate was reduced; The vitality of SOD and GSH-Px increased significantly, and the difference was statistically significant ( P <0.05) . At the same time, the level of MDA and H(2)O(2) and the activity of extracellular LDH enzyme were significantly reduced, and the difference was statistically significant ( P <0.05) . The results showed that nickel refining dust induced cell damage through up-regulation of p53 protein and down-regulation of Bcl-2 protein expression; ascorbic acid interventions, the expression level of Bcl-2 protein in ascorbic acid II and III groups was higher than that of nickel refining dust group, and the difference was statistically significant ( P <0.05); The expression level of p53 protein in each dose group of ascorbic acid was lower than that of nickel refined dust group, and the difference was statistically significant ( P <0.05). Conclusion: With the increase of concentration of ascorbic acid, oxidative damage levels, antioxidant enzyme levels, reduce cell apoptosis, reduce expression of p53, increased expression of Bcl-2. It showed that ascorbic acid had protective effect on NIH/3T3 cell injury induced by nickel refining dust.

The oxidative stress that evolves under cobalt and nickel exposure is thought to exert toxicity, though the exact routes of such metal poisoning remain ambiguous. We revisited the metal toxicity in Escherichia coli to show that cobalt and nickel exposure at levels as low as 0.5 and 1 mM, respectively, visibly inhibits growth. We also observed that acidic conditions aggravated, while alkaline conditions alleviated the metal toxicity. Besides, 1 mM manganese, which is non-cytotoxic, as judged by the growth of E. coli, synergistically elevated cobalt and nickel stress. However, the metal toxicity did not lead to oxidative stress in E. coli. On the other hand, we show that cobalt and nickel, but not manganese, reduced the rate of DNA replication to 50% within 2 hours. Interestingly, the metal ions promoted DNA double-strand breaks but did not induce SOS repair pathways, indicating that the metal ions could block SOS induction. To test this, we show that cobalt and nickel, but not manganese, suppressed the nalidixic acid-induced SOS response. Finally, using an in vitro assay system, we demonstrated that cobalt and nickel inhibit RecBCD function, which is essential for SOS induction. Therefore, our data indicate that cobalt and nickel affect DNA replication, damage DNA, and inhibit the SOS repair pathway to exert toxicity.

Nickel has been found a key pollutant in farmlands of central and south China, and understanding of Ni toxicity in rice is of great significance in safety production of rice and remediation of Ni polluted paddy soils. The present study aimed to investigate the uptake and subcellular distribution of Ni, antioxidant production, and osmolyte accumulation of rice (Oryza sativa L., cv. yangliangyou 6) plants exposed to excessive Ni concentrations to gain an insight into Ni-induced phytotoxicity. Results revealed that exposure of rice seedlings to high Ni concentrations resulted a decline in root and shoot lengths and fresh weight (FW) and dry weight (DW) of rice plants, which are in connection with the depletion of the contents of photosynthetic pigments. Measurement of Ni concentrations in the roots and shoots showed that Ni was mainly accumulated in roots followed by shoots. Moreover, Ni was mainly deposited in soluble fraction and cell wall, than cell organelle, which suggests that both compartments act as crucial defensive barriers against Ni toxicity in rice plants. Ni also induced its toxicity by damaging oxidative metabolism, as indicated by increased level of hydrogen peroxide and malondialdehyde content. Furthermore, Ni stress also showed a desynchronized antioxidant system by increasing the activities of catalase, peroxidase, and the contents of ascorbic acid and glutathione, whereas decreasing the activity of superoxide dismutase in the roots and shoots of rice plants. Ni stress also triggered the rate of proline accumulation and decreasing the contents of soluble protein and soluble sugar. In crux, our results suggests that excessive Ni inhibited rice growth and induced oxidative stress through inducing ROS formation, while stimulated enzymatic and non-enzymatic antioxidants system appeared as adaptive mechanisms of rice plants against Ni-induced oxidative stress. Furthermore, majority of Ni was located in soluble fraction and modulation in osmolyte accumulation under Ni stress seemed to provide additional defense against oxidative stress.

The alleviation effect of exogenous melatonin (MT) on Ni toxicity in rice seedings was investigated. The results showed that low concentration of Ni stress (10, 50 μmol·L -1 ) had little effect on the growth of root of rice seedings, while higher concentration of Ni stress (100-1000 μmol·L -1 ) significantly inhibited the growth of rice root. Compared with the control treatment, the addition of 100 and 1000 μmol·L -1 Ni would decrease the total length and surface area of root by 63.3%-98.0% and 56.9%-96.3%, respectively. The results showed that addition of exogenous melatonin had a positive effect on the growth of rice seedings under Ni stress. This kind of positive effect was even more obvious in the root of rice seedings. The total length of rice root decreased by 58.4%-83.8% at Ni concentration of 100 μmol·L -1 , whereas it decreased by only 8.7%-29.1% when 100 μmol·L -1 Ni and 10 μmol·L -1 MT were added, compared with the control treatment. The addition of exogenous melatonin had significant alleviation effects on oxidative stress in rice seedings caused by Ni. Compared with the 100 μmol·L -1 Ni treatment, addition of 10 μmol·L -1 exogenous MT could significantly decrease the production rate of O 2 -· by 43.2%-50.2% and the relative electrolytic leakage by 25.7%-31.6%, whereas increase the activities of CAT by 21.9%-33.7% and the soluble protein content by 82.6%-84.6%. The results suggested that application of exogenous melatonin could effectively alleviate the toxic effects of Ni on rice seedings.

A freshwater microalga strain of Chlorella vulgaris was used to investigate toxic effects induced by nickel oxide nanoparticles (NiO-NPs) in suspension. Algal cells were exposed during 96 h to 0-100 mg L -1 of NiO-NPs and analyzed by flow cytometry. Physicochemical characterization of nanoparticles in tested media showed a soluble fraction (free Ni 2+ ) of only 6.42% for 100 mg L -1 of NiO-NPs, indicating the low solubility capacity of these NPs. Toxicity analysis showed cellular alterations which were related to NiO-NPs concentration, such as inhibition in cell division (relative cell size and granularity), deterioration of the photosynthetic apparatus (chlorophyll synthesis and photochemical reactions of photosynthesis), and oxidative stress (ROS production). The change in cellular viability demonstrated to be a very sensitive biomarker of NiO-NPs toxicity with EC 50 of 13.7 mg L -1 . Analysis by TEM and X-ray confirmed that NiO-NPs were able to cross biological membranes and to accumulate inside algal cells. Therefore, this study provides a characterization of both physicochemical and toxicological properties of NiO-NPs suspensions in tested media. The use of the freshwater strain of C. vulgaris demonstrated to be a sensitive bioindicator of NiO-NPs toxicity on the viability of green algae.

We investigated changes in nuclear factor kappa B (NFkB) activity, antioxidant responses and histopathological effects in the liver, gill and kidney tissues of rainbow trout exposed to nickel chloride (Ni). Two different concentrations (1 mg/L and 2 mg/L) were administrated to fish for 21 days. Tissues were taken from all fish for NFkB activity, histopathological examination and determination of superoxide dismutase (SOD), catalase (CAT) enzyme activity and of lipid peroxidation (LPO), and glutathione (GSH) levels. The findings of this study indicated that Ni exposure led to a significant increase in LPO indicating peroxidative damage and antioxidant enzymes SOD and CAT activity in tissues (p < 0.05), but 2 mg/Ni concentration caused a significant decrease in CAT activity in kidney tissues (p < 0.05). One of mechanism in the antioxidant defense system seems to be GSH, which increased in gill and kidney tissues of fish exposed to Ni (p < 0.05). NFkB immunopositivity was detected in all tissues. Ni exposure caused lamellar thickening, cellular infiltration in gill tissues, hydropic degeneration of hepatocytes in liver tissues, hyalinous accumulation within the glomeruli and tubular degeneration in kidney tissues. Our results suggested that Ni toxicity may disturb the biochemical and physiological functions of fish by causing changes in NFkB activity and oxidative and histopathological damage in the tissues of rainbow trout. This study can provide useful information for understanding of Ni-induced toxicity., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Inanga (Galaxias maculatus) are a euryhaline and amphidromous Southern hemisphere fish species inhabiting waters highly contaminated in trace elements such as nickel (Ni). Ni is known to exert its toxic effects on aquatic biota via three key mechanisms: inhibition of respiration, impaired ion regulation, and stimulation of oxidative stress. Inanga acclimated to freshwater (FW), 50% seawater (SW) or 100% SW were exposed to 0, 150 or 2000 μg Ni L(-1), and tissue Ni accumulation, metabolic rate, ion regulation (tissue ions, calcium (Ca) ion influx), and oxidative stress (catalase activity, protein carbonylation) were measured after 96 h. Ni accumulation increased with Ni exposure concentration in gill, gut and remaining body, but not in liver. Only in the gill was Ni accumulation affected by exposure salinity, with lower branchial Ni burdens in 100% and 50% SW inanga, relative to FW fish. There were no Ni-dependent effects on respiration, or Ca influx, and the only Ni-dependent effect on tissue ion content was on gill potassium. Catalase activity and protein carbonylation were affected by Ni, primarily in FW, but only at 150 μg Ni L(-1). Salinity therefore offsets the effects of Ni, despite minimal changes in Ni bioavailability. These data suggest only minor effects of Ni in inanga, even at highly elevated environmental Ni concentrations., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Nickel is an environmental pollutant that adversely affects the male reproductive system. In the present study, the effects of nickel exposure on Spodoptera litura Fabricius were investigated by feeding larvae artificial diets containing different doses of nickel for three generations. Damage to testes and effects on male reproduction were examined. The amount of nickel that accumulated in the testes of newly emerged males increased as the nickel dose in the diet increased during a single generation. Nickel exposure increased the amount of thiobarbituric acid reactive substances and decreased the amount of glutathione in treatment groups compared with the control. The activity levels of the antioxidant response indices superoxide dismutases, catalase, and glutathione peroxidase in the testes showed variable dose-dependent relationships with nickel doses and duration of exposure. Nickel doses also disrupted the development of the testes by decreasing the weight and volume of testes and the number of eupyrene and apyrene sperm bundles in treatment groups compared with the control. When the nickel-treated males mated with normal females, fecundity was inhibited by the higher nickel doses in all three generations, but fecundity significantly increased during the second generation, which received 5 mg kg(-1) nickel. Hatching rates in all treatments significantly decreased in a dose-dependent manner in the three successive generations. The effects of nickel on these parameters correlated with the duration of nickel exposure. Results indicate assays of testes may be a novel and efficient means of evaluating the effects of heavy metals on phytophagous insects in an agricultural environment., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Nickel (Ni), one of hazardous environmental chemicals, is known to cause liver injury. Accumulating evidence showed that puerarin (PU) possessed comprehensive biological effects. The purpose of the current study was to test the hypothesis that the puerarin protects against enhanced liver injury caused by Ni in mice. ICR mice received intraperitoneally nickel sulfate (20 mg/kg/body weight, daily) for 20 days, and puerarin (200 and 400 mg/kg/body weight) was applied before Ni exposure. The results indicated that puerarin markedly inhibited Ni-induced liver injury, which was characterized by decreased aminotransferase activities and inflammation. Puerarin also inhibited the oxidative stress and decreased the metallothionein (MT) levels. Puerarin decreased the level of pro-inflammatory cytokines TNF-α and IL-6 in livers. Puerarin significantly inhibited the TLR4 activation and p38 MAPK phosphorylation, which in turn inhibited NF-κB activity. Likewise, Ni-induced inflammatory responses were diminished by puerarin as observed by a remarkable reduction in the levels of phosphorylated CREB. Furthermore, puerarin also reduced inflammatory mediators such as cyclooxygenase-2 (COX-2) and prostaglandin E2 (PGE2) levels in livers. Data from this study suggested that the inhibition of Ni-induced oxidative stress and inflammatory responses by puerarin is due to its ability to modulate the TLR4/p38/CREB signaling pathway., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Nickel (Ni)-induced oxidative damage is a serious problem that leads to reproductive system failure through testicular damage. The present investigation was carried out to determine the effect of troxerutin (Txn) on testicular toxicity induced by Ni in experimental rat testes. The oral administration of Txn (100 mg/kg body weight [bw]) showed a significant (p < 0.01) increase in superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione-S-transferase (GST), glutathione reductase (GR), glucose-6-phosphate dehydrogenase (G6PD), reduced glutathione, ascorbate, total sulphydryl groups, and testis-organ weight. Subsequently, the administration of Txn also significantly reduced the accumulation of Ni, lipid peroxidation products, and protein carbonyl levels in Txn-treated animals. Testicular protection in the experimental animals by Txn is further substantiated by a remarkable reduction of Ni, which was revealed through testicular tissue histopathology. These studies suggest that Txn could prevent oxidative damage and testicular toxicity induced by Ni in experimental animals.

The aim of this study was to determine the biochemical, immunohistochemical, and histopathological effects of nickel chloride (Ni) in the rainbow trout brain. Fish were exposed to Ni concentrations (1 mg/L and 2 mg/L) for 21 days. At the end of the experimental period, brain tissues were taken from all fish for c-Fos activity and histopathological examination and determination of acetylcholinesterase (AChE), superoxide dismutase (SOD), catalase (CAT) enzyme activities, lipid peroxidation (LPO), and glutathione (GSH) levels. Our results showed that Ni treatment caused a significant increase in the brain SOD activity and in LPO and GSH levels (p < 0.05), but it significantly decreased AChE and CAT enzyme activities (p < 0.05). Strong induction in c-Fos was observed in some cerebral and cerebellar regions of fish exposed to Ni concentrations when compared with the control group. However, c-Fos activity was decreased in necrotic Purkinje cells. Brain tissues were characterized by demyelination and necrotic changes. These results suggested that Ni treatment causes oxidative stress, changes in c-Fos activity, and histopathological damage in the fish brain.

The mechanisms of nickel (Ni) toxicity in marine fish remain unclear, although evidence from freshwater (FW) fish suggests that Ni can act as a pro-oxidant. This study investigated the oxidative stress effects of Ni on the euryhaline killifish (Fundulus heteroclitus) as a function of salinity. Killifish were exposed to sublethal levels (5, 10, and 20 mg L(-1)) of waterborne Ni for 96 h in FW (0 ppt) and 100 % saltwater (SW) (35 ppt). In general, SW was protective against both Ni accumulation and indicators of oxidative stress [protein carbonyl formation and catalase (CAT) activity]. This effect was most pronounced at the highest Ni exposure level. For example, FW intestine showed increased Ni accumulation relative to SW intestine at 20 mg Ni L(-1), and this was accompanied by significantly greater protein carbonylation and CAT activity in this tissue. There were exceptions, however, in that although liver of FW killifish at the highest exposure concentration showed greater Ni accumulation relative to SW liver, levels of CAT activity were greatly decreased. This may relate to tissue- and salinity-specific differences in oxidative stress responses. The results of the present study suggest (1) that there was Ni-induced oxidative stress in killifish, (2) that the effects of salinity depend on differences in the physiology of the fish in FW versus SW, and (3) that increased levels of cations (sodium, calcium, potassium, and magnesium) and anions (SO4 and Cl) in SW are likely protective against Ni accumulation in tissues exposed to the aquatic environment.

The aim of the present study was to assess the oxidative stress, antioxidant response and histopathological changes of nickel nanoparticles (Ni NPs) exposure (14 days) in Mozambique tilapia, Oreochromis mossambicus. Ni NPs were synthesized by metal salt reduction method and characterized by X-ray diffraction (XRD) and Transmission electron microscopy (TEM). The XRD peaks at 44°, 51° and 76° were indexed to the (111), (200) and (220) Bragg's reflections of cubic structure of Nickel, respectively. The crystallite sizes were calculated using Scherrer's formula applied to the major intense peaks and found to be the size of 56nm. TEM images showed that the synthesized Ni NPs are spherical in shape. Biochemical analysis indicated that the superoxide dismutase (SOD), catalase (CAT) and peroxidase (POD) activity was significantly affected by Ni NPs treated O. mossambicus. Reduced antioxidant enzymes and the contents of antioxidants were lowered in the liver and gills of fishes treated with Ni NPs. After 14 days of exposure, a significant accumulation of Ni in the Ni NPs in experimental group was observed in the gill and skin tissues, with the highest levels found in the liver. Ni NPs exposed fish showed nuclear hypertrophy (NH), nuclear degeneration (ND), necrosis (NC) and irregular-shaped nuclei were observed in liver tissue. The hyperplasia of the gill epithelium (GE), lamellar fusion of secondary lamellae (LF), dilated marginal channel (MC), epithelial lifting (EL) and epithelial rupture were observed in gill tissue. Degeneration in muscle bundles (DM), focal area of necrosis (NC) vacuolar degeneration in muscle bundles (VD), edema between muscle bundles (ED) and splitting of muscle fibers were noticed in skin tissue. Further ecotoxicological evaluation will be made concerning the risk of Ni NPs on aquatic environment., (Copyright © 2014 Elsevier Inc. All rights reserved.)

In this experiment, we studied the transcriptional and functional (enzymatic) responses of yellow perch (Perca flavescens) to metal stress, with a focus on oxidative stress and vitamin A metabolism. Juvenile yellow perch were exposed to two environmentally relevant concentrations of waterborne cadmium (Cd) and nickel (Ni) for a period of 6 weeks. Kidney Cd and Ni bioaccumulation significantly increased with increasing metal exposure. The major retinoid metabolites analyzed in liver and muscle decreased with metal exposure except at high Cd exposure where no variation was reported in liver. A decrease in free plasma dehydroretinol was also observed with metal exposure. In the liver of Cd-exposed fish, both epidermal retinol dehydrogenase 2 transcription level and corresponding enzyme activities retinyl ester hydrolase and lecithin dehydroretinyl acyl transferase increased. In contrast, muscle epidermal retinol dehydrogenase 2 transcription level decreased with Cd exposure. Among antioxidant defences, liver transcription levels of catalase, microsomal glutathione-S-transferase-3 and glucose-6-phosphate dehydrogenase were generally enhanced in Cd-exposed fish and this up-regulation was accompanied by an increase in the activities of corresponding enzymes, except for microsomal glutathione-S-transferase. No consistent pattern in antioxidant defence responses was observed between molecular and biochemical response when fish were exposed to Ni, suggesting a non-synchronous response of antioxidant defence in fish exposed to waterborne Ni. There was a general lack of consistency between muscle transcription level and enzyme activities analyzed. The overall findings from this investigation highlight the usefulness of transcriptional and biochemical endpoints in the identification of oxidative stress and vitamin A metabolism impairment biomarkers and the potential use of multi-level biological approaches when assessing environmental risk in fish., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Welding processes that generate fumes containing toxic metals, such as hexavalent chromium (Cr(VI)), manganese (Mn), and nickel (Ni), have been implicated in lung injury, inflammation, and lung tumor promotion in animal models. While federal regulations have reduced permissible worker exposure limits to Cr(VI), this is not always practical considering that welders may work in confined spaces and exhaust ventilation may be ineffective. Thus, there has been a recent initiative to minimize the potentially hazardous components in welding materials by developing new consumables containing much less Cr(VI) and Mn. A new nickel (Ni) and copper (Cu)-based material (Ni-Cu WF) is being suggested as a safer alternative to stainless steel consumables; however, its adverse cellular effects have not been studied. This study compared the cytotoxic effects of the newly developed Ni-Cu WF with two well-characterized welding fumes, collected from gas metal arc welding using mild steel (GMA-MS) or stainless steel (GMA-SS) electrodes. RAW 264.7 mouse macrophages were exposed to the three welding fumes at two doses (50 µg/ml and 250 µg/ml) for up to 24 hours. Cell viability, reactive oxygen species (ROS) production, phagocytic function, and cytokine production were examined. The GMA-MS and GMA-SS samples were found to be more reactive in terms of ROS production compared to the Ni-Cu WF. However, the fumes from this new material were more cytotoxic, inducing cell death and mitochondrial dysfunction at a lower dose. Additionally, pre-treatment with Ni-Cu WF particles impaired the ability of cells to phagocytize E. coli, suggesting macrophage dysfunction. Thus, the toxic cellular responses to welding fumes are largely due to the metal composition. The results also suggest that reducing Cr(VI) and Mn in the generated fume by increasing the concentration of other metals (e.g., Ni, Cu) may not necessarily improve welder safety.

Objective: To investigate the cytotoxicity and oxidative damage on NIH/3T3 cells induced by nickel smelting fume., Methods: NIH/3T3 cells were treated with nickel smelting fume collected from a nickel smelting factory in China with doses of 0, 6.25, 12.50, 25.00, 50.00, and 100.00 µg/ml for 6 h. Dose-dependent cytotoxicity in cells were assessed by Cell Counting Kit-8 (CCK-8), natural red uptake assay, and lactate dehydrogenase (LDH) leakage assay, and the level of oxidative damage was assessed based on the activity of catalase (CAT), percentage inhibition of superoxide dismutase (SOD), and content of malonaldehyde (MDA)., Results: The relative survival of NIH/3T3 cells decreased with the increase in the dose of nickel smelting fume. In the CCK-8 assay, the group with 100 µg/ml nickel smelting fume showed a cell growth inhibition rate of 86%, with a significant difference compared with the control group (P < 0.05). LDH activity increased with increasing dose of nickel smelting fume: the groups of 12.50, 25, 50, and 100 µg/ml nickel smelting fume all showed increased LDH activities as compared with the control group (P < 0.05). The activities of CAT were significantly reduced in groups of 25, 50, and 100 µg/ml nickel smelting fume as compared with that of the control group (P < 0.05). As the dose of nickel smelting fume increased, the percentage inhibition of SOD and the content of MDA increased, with significant differences compared with the control group (P < 0.05)., Conclusion: Oxidative damage may be induced in NIH/3T3 cells after 6 h of exposure to nickel smelting fume, which leads to cell death.

After 96 h goldfish exposure to 10, 25 or 50 mg/L of Ni(2+) no Ni accumulation was found in the brain, but lipid peroxide concentration was by 44% elevated in the brain, whereas carbonyl protein content was by 45-45% decreased in the heart. High molecular mass thiol concentration was enhanced by 30% in the heart, while in the brain low molecular mass thiol concentration increased by 28-88%. Superoxide dismutase activity was by 27% and 35% increased in the brain and heart, respectively. Glutathione peroxidase activity was lowered to 38% and 62% of control values in both tissues, whereas catalase activity was increased in the heart by 15-45%, accompanied by 18-29% decreased glutathione reductase activity. The disturbances of free radical processes in the brain and heart might result from Ni-induced injuries to other organs with more prominent changes in the heart, because of close contact of this organ with blood, whereas the blood-brain barrier seems to protect the brain., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Nickel and nickel compounds are carcinogens that target the lungs and kidneys causing cell death or cell survival adaptation. The multidrug resistance P-glycoprotein ABCB1 protects cells against toxic metabolites and xenobiotics and is upregulated in many cancer cell types. Here, we investigated the role of ABCB1 in nickel-induced stress signaling mediated by reactive oxygen species (ROS) and ceramides. In renal proximal tubule cells, nickel chloride (0.1-0.25 mM) increased both ROS formation, detected by 5-(and-6)-carboxy-2',7'-dichlorodihydrofluorescein diacetate, and cellular ceramides, which were determined by lipid dot blot and surface immunostaining, culminating in decreased cell viability, increased DNA fragmentation, augmented PARP-1 cleavage, and increased ABCB1 mRNA and protein. Inhibitors of the de novo ceramide synthesis pathway (fumonisin B1, L-cycloserine) and an antioxidant (α-tocopherol) attenuated nickel-induced toxicity as well as induction of ABCB1. ABCB1 protects against nickel toxicity as PSC833, an ABCB1 blocker, augmented the decrease in cell viability by nickel. Moreover, nickel toxicity was attenuated in renal MDCK cells stably overexpressing ABCB1. In agreement with previous data that demonstrated extrusion of (glucosyl)ceramides by ABCB1 (Lee et al. in Toxicol Sci 121:343, 2011), PSC833 increased total cellular ceramides by >2-fold after nickel treatment. Further, glucosylceramide synthase (GCS) mRNA is upregulated by nickel at 3 h by ~1.5-fold but declined with prolonged exposures (6-24 h). Inhibition of GCS with C9DGJ or knockdown of GCS with siRNA significantly attenuated nickel toxicity. In conclusion, nickel induces a ROS-ceramide pathway to cause apoptotic cell death as well as activate adaptive survival responses, including upregulation of ABCB1, which improves cell survival by extruding proapoptotic (glucosyl)ceramides.

The present study aims to evaluate transcriptional expression levels and biochemical markers of oxidative stress responses to nickel (Ni) exposure along with heat stress gradient in a mussel (Mytilus galloprovincialis). For this purpose, we investigated the response of oxidative stress markers, metallothionein accumulation and gene expression in digestive gland of mussels exposed to a sublethal concentration of Ni (2.5μM) along with a temperature gradient (18°C, 22°C, and 26°C) for 24h and 72h. Ni digestive gland uptake was evaluated after the exposure periods. Co-exposure to Ni and higher temperature (26°C) for 72h significantly decreased the antioxidant enzyme activities termed as catalase (CAT), superoxide dismutase (SOD) and glutathione-S-transferase (GST) and caused a pronounced increase of lipofuscin and neutral lipid (NL) accumulation. Ni-uptake was different with respect to the exposure periods and temperatures in Ni-exposed mussels. Sod, cat, gst, mt-10 and mt20 gene expression levels showed a substantial increased pattern in animals exposed for one day to heat stress compared to the control condition (18°C). The same pattern but with highest level was registered in animals co-exposed to Ni and temperatures within one day. Three days exposure to 18°C, 22°C and 26°C, resulted in a significant decrease in mRNA abundance of cat, gst and sod and a significant down-regulation of mts targets (22°C and 26°C). Our data provide new insights into the importance of the early protective response of oxidative stress related-gene expression and regulation in mussels challenging heat stress and sublethal Ni concentration., (Copyright © 2013. Published by Elsevier Inc.)

Objective: This study aimed to evaluate the effects of toxic heavy metal co-exposure on DNA oxidative damage in neonates from a primitive e-waste recycling region, Guiyu town, China., Methods: Our participants included 201 pregnant women: 126 from Guiyu town and 75 from Jinping district of Shantou city, where no e-waste recycling and dismantling activities existed. Structured interview questionnaires were administered to the pregnant women and umbilical cord blood (UCB) samples were collected after delivery. The UCB concentrations of lead, cadmium, chromium, and nickel were analyzed by graphite furnace atomic absorption spectrometry (GFAAS). Levels of UCB plasma 8-hydroxydeoxyguanosine (8-OHdG, a DNA oxidative damage biomarker) were determined by enzyme-linked immunosorbent assay., Results: Our results suggested that UCB lead and cadmium concentrations in neonates of Guiyu were significantly higher than those of Jinping (lead: median 110.45 ng/mL vs. 57.31 ng/mL; cadmium: median 2.50 ng/mL vs. 0.33 ng/mL, both P<0.001). Parents' residence in Guiyu, and parents' work related to e-waste recycling were the risk factors associated with neonate's UCB lead and cadmium levels. No significant difference of UCB plasma 8-OHdG levels was found between Guiyu and the control area. After adjusting for potential confounders, cord plasma 8-OHdG concentrations (ng/mL) were positively associated with blood cadmium (β=0.126 ng/mL, 95% CI: 0.055 to 0.198 ng/mL), chromium (β=0.086 ng/mL, 95% CI: 0.014 to 0.158 ng/mL) and nickel (β=0.215 ng/mL, 95% CI: 0.113 to 0.317 ng/mL) concentrations., Conclusions: The primitive e-waste recycling and dismantling activities may contribute to the elevated umbilical cord blood toxic heavy metal levels in neonates born in Guiyu. Exposures to cadmium, chromium and nickel were associated with increased oxidative DNA damage in neonates., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Nickel (Ni) is ubiquitous in the biosphere and is a common component of natural fresh waters. When present in high concentrations, it becomes toxic to aquatic organisms. It is known that Ni toxicity may induce oxidative stress and apoptosis. However, the precise mechanism and the pathways that are activated in fish are still unclear. Thus, this study aimed to assess which apoptotic pathways are triggered by Ni in Carassius auratus liver, the main target of waterborne pollutants. Fish were exposed to 10, 25, 50 and 100mg/L of nickel sulfate for 96 h. Our data showed that Ni exposure caused fish weight loss (by 10-12%) and decreased locomotory activity (by 1-25%). Ni exposure significantly decreased the relative lymphocyte count (by 1-24%) and increased the relative count of monocytes (by 25-111%) and neutrophils (by 10-322%) as compared to controls. Ni induced oxidative stress, as evidenced by increasing of lipid peroxidation level (29-91%) and depleting of the glutathione levels (7-79%) in fish liver. Ni also suppressed the activities of superoxide dismutase (by 39-55%) and glutathione peroxidase (16-24%) and decreased ATP levels (13-51%) in livers. Moreover, liver caspase-3, one of the key executioners of apoptosis, was markedly activated by the Ni exposure. Ni exposure also increased expression levels of phosphorylated Jun N-terminal kinases (JNK) in liver, which in turn activated pro-apoptotic signaling events by breaking the balance between pro-apoptotic and anti-apoptotic Bcl-2 proteins. In conclusion, these results suggested that Ni induced oxidative stress and apoptosis, at least, via the JNK signaling pathway., (Copyright © 2014 Elsevier B.V. All rights reserved.)

The purpose of this study was to investigate the effects of dietary NiCl2 on antioxidant function, apoptosis, and the protein expression, mRNA expression and contents of the bcl-2, bax and caspase-3 in the cecal tonsil of broilers. 280 one-day-old avian broilers were divided into four groups and fed on a corn-soybean basal diet as control diet or the same basal diet supplemented with 300, 600 and 900 mg/kg of NiCl2 for 42 days. The activities of SOD, CAT and GSH-Px, and the ability to inhibit hydroxy radical, and GSH content were significantly decreased in all experimental groups. MDA content was significantly increased. The protein expression, mRNA expression and contents of bcl-2 were decreased, and bax and caspase-3 were increased in all experimental groups. The percentages of apoptotic lymphocytes were significantly increased. In conclusion, dietary NiCl2 in excess of 300 mg/kg caused oxidative stress, and then induced decreased the protein expression, mRNA expression and the contents of bcl-2, and increased protein expression, mRNA expression and the contents of bax and caspase-3 proteins in the cecal tonsil. The local intestinal mucosal immunity could finally be impaired due to the oxidative stress and apoptosis in the cecal tonsil caused by NiCl2., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Two hundred and forty avian broilers were equally divided into four groups, and raised with a corn-soybean basal diet or the same diet supplemented with 300, 600, 900 mg/kg NiCl2 for 42 days. Numbers or percentages of apoptotic splenocytes by flow cytometry (FCM) and TUNEL were higher (p < 0.05 or p < 0.01) in the 300, 600 and 900 mg/kg groups than those in the control group. Results measured by qRT-PCR and ELISA showed that mRNA expression and contents were significantly higher (p < 0.05 or p < 0.01) in Bax and Caspase-3, and were significantly lower (p < 0.05 or p < 0.01) in Bcl-2 of the 300, 600 and 900 mg/kg groups. Also, the SOD, CAT and GSH-Px activities, and the ability to inhibit hydroxyl radical, and GSH contents were significantly decreased (p < 0.05 or p < 0.01), and MDA contents were increased (p < 0.05 or p < 0.01) in all groups. In conclusion, dietary NiCl2 in excess of 300 mg/kg caused apoptosis, altered Bax, Bcl-2 and Caspase-3 mRNA expression levels and contents, and induced oxidative stress in the spleen. Also, splenocyte apoptosis was closely related to the alternations of Bax, Bcl-2 and Caspase-3 mRNA expression, and oxidative damage. The splenic immunity and blood filtration functions were impaired in broilers.