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Obesity is a risk factor of many diseases, but could be beneficial to the individuals with bacterial infection. The present study was conducted to investigate the relationship between obesity and heart during nonfatal bacterial infection. Male normal (lean) and diet-induced obesity mice (DIO, fed with high-fat diet) were chosen to perform nasal instillation with E. coli to establish a nonfatal acute mouse model. The cardiac histopathology, inflammation and oxidative damage, as well as apoptosis were detected post-infection. The results revealed that the Escherichia coli (E.coli)-infected mice exhibited increased cardiac index, contents of IL-1β, IL-6, IL-8, TNF-α, leptin and resistin, levels of apoptotic proteins (caspase-3 and caspase-9, and bax/bcl-2 ratio), cardiac pathological changes and oxidative stress. Furthermore, these parameters were more serious in the lean mice than those in the DIO mice. In summary, our findings gave a new sight that E.coli infection impaired heart via histopathological lesions, inflammation and oxidative stress and excessive apoptosis of cardiomyocytes. Interestingly, obesity exerted attenuated effects on the heart of mice with non-fatal infection of E.coli through decreased inflammation, oxidative stress and apoptosis of cardiac tissue., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Copper is considered as an indispensable trace element for living organisms. However, over-exposure to Cu can lead to adverse health effects on human. In this study, CuSO 4 decreased sperm concentration and motility, increased sperm malformation rate. Concurrently, testicular damage including testicular histopathological aberrations and reduction of testis relative weight were observed. Then, the mechanism underlying Cu-induced testicular toxicity was explored. According to the results, CuSO 4 elevated ROS production while reducing antioxidant function. Additionally, CuSO 4 induced apoptosis which was featured by MMP depolarization and up-regulated levels of cleaved-caspase-3, cleaved-caspase-8, cleaved-caspase-9, caspase-12, cleaved-PARP and Bax, whereas down-regulated Bcl-2 expression. Meanwhile, CuSO 4 caused testis DNA damage (up-regulation of γ-H2AX protein expression) and suppressed DNA repair pathways including BER, NER, HR, MMR, together with the NHEJ repair pathways, yet did not affect MGMT. To investigate the role of oxidative stress in CuSO 4 -induced apoptosis and DNA damage, the antioxidant NAC was co-treated with CuSO 4 . NAC attenuated CuSO 4 -induced ROS production, inhibited apoptosis and DNA damage. Furthermore, the spermatogenesis disorder was also abolished in the co-treatment with CuSO 4 and NAC group. Altogether, abovementioned results indicated that CuSO 4 -induced spermatogenesis disorder is related to oxidative stress-mediated DNA damage and germ cell apoptosis, impairing male reproductive function., (Copyright © 2021 Elsevier B.V. All rights reserved.)

The destruction of biological activity such as senescence and apoptosis caused by oxidative stress could play a pivotal role in the poor therapeutic efficiency of bone marrow mesenchymal stem cells (BMSCs) transplantation. Mitoquinone (MitoQ) has a highly effective mitochondrial antioxidant effect, and has been widely used in many oxidative damage models. This study aimed to investigate the protective effect of MitoQ on the oxidative stress-mediated senescence of canine BMSCs and the underlying mechanism. The senescence of BMSCs was determined by senescence-associated β-galactosidase staining and quantitative real-time PCR. The expression of p-Nrf2 protein was detected by Western blotting. The results demonstrated that, as BMSCs were expanded in vitro, the senescent phenotype appeared. And the senescence of BMSCs may be caused by oxidative stress, manifested by increasing the level of ROS and decreasing the activity of antioxidant enzymes. Treatment of MitoQ down-regulated the mRNA levels of senescence-related and apoptosis-related genes, but up-regulated the mRNA levels of proliferation-related genes. Meanwhile, ROS generation and senescent activity were reduced in MitoQ-treated BMSCs. Further mechanism studies showed that MitoQ obviously promoted Nrf2 phosphorylation, and also facilitated the translocation of Nrf2 into the nucleus. Moreover, treatment of MitoQ increased the mRNA levels of downstream antioxidant genes and enhanced the activities of superoxide dismutase, catalase, and glutathione peroxidase. Thus, our study revealed that MitoQ, via the Nrf2/ARE signaling pathway, exerts an antioxidant effect as well as potentially delays OS-mediated senescence during BMSCs that were expanded in vitro, which may serve as a novel strategy to optimize the clinical application of BMSCs., (© 2021. The Society for In Vitro Biology.)

Hepatic oxidative stress, as one important mechanism of cadmium (Cd)-induced hepatic toxicity, could, as known, be ameliorated by vitamin E (VE). However, the underlying mechanism remains to be elucidated. To investigate whether the antioxidant vitamin E can protect against Cd-induced sub-chronic liver injury associated with oxidative stress and nuclear factor erythrocyte 2-related factor 2 (Nrf2) pathway, male Sprague-Dawley rats (nine-week-old) were randomly divided into four groups (eight rats/group), namely, control, VE (100 mg/kg VE), Cd (5 mg/kg CdCl 2 ) and VE+Cd (100 mg/kg VE+5 mg/kg CdCl 2 ), and received intragastric administration of Cd and/or VE for four weeks. Cd-exposure alone resulted in reduced liver weight, liver histological alteration and oxidative stress, accumulation of Cd in the liver, elevated ALT and AST concentrations in serum together with decreased mRNA and protein expressions of Nrf2 pathway related molecules (Nrf2, HO-1, NQO-1, GCLC, GCLM and GST). However, the co-treatment of Cd and VE significantly ameliorated the changes mentioned above, and promoted the expression of genes and proteins of Nrf2 pathway related molecules in comparison to the Cd-exposure alone. Our results indicate that the protective effect of VE against Cd-induced sub-chronic hepatic damage in rats is associated with the inhibition of oxidative stress and activation of Nrf2 pathway., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Copper (Cu) is an essential trace element involved in the normal physiological processes of animals. However, excessive exposure to Cu can produce numerous detrimental impacts. The aim of this study was to investigate the effects of Cu on oxidative stress and apoptosis as well as their relationship in the mouse liver. Four-week-old ICR mice ( n = 240) were randomly assigned to different Cu (Cu2+-CuSO4) treatment groups (0, 4, 8, and 16 mg/kg) for periods of 21 and 42 days. The high doses of Cu exposure could induce oxidative stress, by increasing the levels of reactive oxygen species (ROS) and protein carbonyls (PC) and decreasing the activities of antisuperoxide anion (ASA) and antihydroxyl radical (AHR) and content of glutathione (GSH), as well as activities and mRNA expression levels of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px). Moreover, high doses of Cu exposure induced hepatic apoptosis via the mitochondrial apoptotic pathway, as characterized by the depolarization of mitochondrial membrane potential (MMP); significantly increased mRNA and protein expression levels of cytosolic cytochrome (Cyt c), apoptosis-inducing factor (AIF), endonuclease G (Endo G), apoptosis protease-activating factor-1 (Apaf-1), cleaved caspase-9, cleaved caspase-3, cleaved PARP, Bcl-2 antagonist killer (Bak), Bcl-2-associated X protein (Bax), and Bcl-2-interacting mediator of cell death (Bim); and decreased mRNA and protein expression levels of B-cell lymphoma-2 (Bcl-2) and Bcl-extra-large (Bcl-xL). Furthermore, the activation of the tumor necrosis factor receptor-1 (TNF-R1) signaling pathway was involved in Cu-induced apoptosis, as characterized by the significantly increased mRNA and protein expression levels of TNF-R1, Fas-associated death domain (FADD), TNFR-associated death domain (TRADD), and cleaved caspase-8. These results indicated that exposure to excess Cu could cause oxidative stress triggered by ROS overproduction and diminished antioxidant function, which in turn promoted hepatic apoptosis via mitochondrial apoptosis and that the TNF-R1 signaling pathway was also involved in the Cu-induced apoptosis., Competing Interests: The authors declare that there are no conflicts of interest., (Copyright © 2020 Huan Liu et al.)

Deoxynivalenol (DON) is a cytotoxic mycotoxin that can cause cell damages. The main effect is to inhibit protein synthesis. Oxidative stress is one of the effects of DON. Selenium (Se) can ameliorate the cell damage caused by DON-induced oxidative stress, but it is unclear whether through selenoprotein glutathione peroxidase 1 (GPX1). We established GPX1-knockdown porcine spleen lymphocytes, and treated them with DON and Se. Untransfected porcine splenic lymphocytes (group P) and transfected cells (group M, GPX1 knockdown) were treated with or without DON (0.824, 0.412, 0.206, or 0.103 μg/mL, group D1-4), Se (Na 2 SeO 3 , 2 μM, group Se), or both (group SD1-4) for 6, 12, or 24 h. The cells were collected and the activities of SOD and CAT, levels of GSH, H 2 O 2 , malonaldehyde (MDA), total antioxidant capacity (T-AOC), and the inhibition of free hydroxyl radicals were determined. Levels of ROS were measured at 24 h. Compared with group P, the antioxidant capacity of group M was reduced. DON caused greater oxidative damage to the GPX1-knockdown porcine splenic lymphocytes than to the normal control cells. When Na 2 SeO 3 was combined with DON, it reduced the damage in the GPX1-knockdown porcine splenic lymphocytes, but less effectively than in the normal porcine splenic lymphocytes.

Deoxynivalenol (DON) and zearalenone (ZEA) are the two most common mycotoxins in animal feed. In this study, we examined oxidative injury and apoptosis of porcine splenic lymphocytes induced by DON or ZEA and their combination in vitro. Based on IC 50 values, porcine splenic lymphocytes were treated with 0.06, 0.3, 1.5, and 7.5μg/mL DON, 0.08, 0.4, 2, and 10μg/mL ZEA, or both DON and ZEA at 0.06 and 0.08μg/mL, 0.3 and 0.4μg/mL, and 1.5 and 2μg/mL, respectively. After 48h of DON and/or ZEA exposure, the cells were analyzed for antioxidant functions, apoptosis, and mRNA and protein expression of apoptosis-related genes p53, Bcl-2, Bax, caspase-3, and caspase-8 to determine their apoptosis and oxidative damage effects and mechanisms. The results showed that, compared with the control group, SOD, CAT, GPx, GSH, and Bcl-2 mRNA and protein expression levels were significantly reduced in exposed groups (P<0.05 or P<0.01). Furthermore, MDA contents, apoptosis rates, and p53, Bax, caspase-3 and caspase-8 protein and mRNA expression levels were increased significantly (P<0.01). The effects of DON and ZEA were dose dependent and synergistic in combination. These data suggest that DON and ZEA induce oxidative damage and apoptosis of porcine splenic lymphocytes., (Copyright © 2017 Elsevier GmbH. All rights reserved.)

The current study was conducted to investigate the effect of sodium fluoride (NaF) on the oxidative stress and apoptosis as well as their relationship in the mouse liver by using methods of flow cytometry, quantitative real-time polymerase chain reaction (qRT-PCR), western blot, biochemistry and experimental pathology. 240 four-week-old ICR mice were randomly divided into 4 groups and exposed to different concentration of NaF (0 mg/kg, 12 mg/kg, 24 mg/kg and 48 mg/kg) for a period of 42 days. The results showed that NaF caused oxidative stress and apoptosis. NaF-caused oxidative stress was accompanied by increasing reactive oxygen species (ROS) and malondialdehyde (MDA) levels, and decreasing mRNA expression levels and activities of superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), glutathione peroxidase (GSH-PX) and glutathione-s-transferase (GST). NaF induced apoptosis via tumor necrosis factor recpter-1 (TNF-R1) signaling pathway, which was characterized by significantly increasing mRNA and protein expression levels of TNF-R1, Fas associated death domain (FADD), TNFR-associated death domain (TRADD), cysteine aspartate specific protease-8 (caspase-8) and cysteine aspartate specific protease-3 (caspase-3) in dose- and time-dependent manner. Oxidative stress is involved in the process of apoptotic occurrence, and can be triggered by promoting ROS production and reducing antioxidant function. NaF-caused oxidative stress and apoptosis finally impaired hepatic function, which was strongly supported by the histopathological lesions and increased serum alanine amino transferase (ALT), aspartic acid transferase (AST), alkaline phosphatase (AKP) activities and TBIL contents.

The purpose of this study was to investigate the histopathological lesions, oxidative damage, changes of immunoglobulin G (IgG), immunoglobulin M (IgM), and immunoglobulin A (IgA) contents in the bursa of Fabricius and serum immunoglobulins (IgG, IgM, IgA) induced by dietary nickel chloride (NiCl2). Two hundred and eighty-one-day-old broilers were randomly divided into four groups and fed on a control diet and three experimental diets supplemented with 300, 600, and 900 mg/kg of NiCl2 for 42 days. Lesions were observed in the NiCl2-treated groups. Histopathologically, lymphocytes were decreased in lymphoid follicles with thinner cortices and wider medullae. Concurrently, the activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), and the ability to inhibit hydroxyl radical and glutathione (GSH) contents were significantly (p < 0.05 or p < 0.01) decreased, while malondialdehyde (MDA) contents were increased in the NiCl2-treated groups. The serum IgG, IgM, and bursa IgG and IgM contents were significantly (p < 0.05 or p < 0.01) lower in the NiCl2-treated groups than those in the control group. The above-mentioned results show that dietary NiCl2 in excess of 300 mg/kg can cause histopathological lesions via oxidative damage, which finally impairs the function of the bursa of Fabricius and reduces IgG and IgM contents of the serum and the bursa of Fabricius. The study is aimed to provide helpful materials for studies on Ni- or Ni compounds-induced B cell toxicity in both human and other animals in the future.

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.

The purpose of this study was to investigate the oxidative damage induced by dietary nickel chloride (NiCl2) in the intestinal mucosa of different parts of the intestine of broilers, including duodenum, jejunum and ileum. A total of 240 one-day-old 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 or 900 mg/kg NiCl2 during a 42-day experimental period. The results showed that the activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px), and the ability to inhibit hydroxy radical and glutathione (GSH) content were significantly (p < 0.05 or p < 0.01) decreased in the 300, 600 and 900 mg/kg groups in comparison with those of the control group. In contrast, malondialdehyde (MDA) content was significantly (p < 0.05 or p < 0.01) higher in the 300, 600 and 900 mg/kg groups than that in the control group. It was concluded that dietary NiCl2 in excess of 300 mg/kg could cause oxidative damage in the intestinal mucosa in broilers, which finally impaired the intestinal functions including absorptive function and mucosal immune function. The oxidative damage might be a main mechanism on the effects of NiCl2 on the intestinal health of broilers.

The purpose of this 42-day study was to investigate the effects of low selenium (Se) on histopathological changes of spleen, cell cycle and apoptosis of splenocytes, and oxidative status of the spleen. One hundred twenty 1-day-old avian broilers were randomly divided into two groups of 60 each and were fed on a low Se diet (0.0342 mg/kg Se) or a control diet (0.2 mg/kg Se), respectively. The weight and relative weight of the spleen were significantly decreased in the low Se group when compared with those of the control group. Histopathologically, splenic lesions in low-Se chicken were characterized by lymphocyte depletion and congestion of red pulp. As measured by flow cytometry, splenocytes in G(0)/G(1) phase were significantly increased, while splenocytes in S phase and G(2) + M phase were obviously decreased in the low Se group. The percentage of apoptotic splenocytes was greatly increased in the low Se group when compared with that of control group. At the same time, the occurrence frequencies of apoptotic splenocytes was markedly increased in the low Se group with the appearance of condensed nucleus ultrastructurally. Oxidative stress in the spleens of the low Se group was evidenced by decrease in glutathione peroxidase and catalase activities and increase in malondialdehyde contents. The results showed that low Se diet intake caused increased apoptosis, arrested cell cycle, and obvious oxidative stress, which provided a possible pathway for the injured structure and immune function of the spleen in chickens.

Three hundred 1-day-old avian broilers were fed on a basic diet (0.2 mg/kg selenium) or the same diet amended to contain 1, 5, 10, and 15 mg/kg selenium supplied as sodium selenite (n = 60/group). In comparison with those of 0.2 mg/kg selenium group, the percentages of annexin V-positive splenocytes were increased in 5, 10, and 15 mg/kg selenium groups. TUNEL assay revealed that apoptotic cells with brown-stained nuclei distributed within the red pulp and white pulp of the spleens with increased frequency of occurrence in 10 and 15 mg/kg selenium groups in comparison with that of 0.2 mg/kg Se group. Sodium selenite-induced oxidative stress in spleens of chickens was evidenced by decrease in glutathione peroxidase, superoxide dismutase, and catalase activities and increase in malondialdehyde contents. The results indicate that excess dietary selenium in the range of 5-15 mg/kg of feed causes oxidative stress, which may be mainly responsible for the increased apoptosis of splenocytes in chickens.

Background/Aims: Excessive fluoride intake can induce cytotoxicity, DNA damage and cell-cycle changes in many tissues and organs, including the kidney. However, the underlying molecular mechanisms of fluoride-induced renal cell-cycle changes are not well understood at present. In this study, we used a mouse model to investigate how sodium fluoride (NaF) induces cell-cycle changes in renal cells. Methods: Two hundred forty ICR mice were randomly assigned to four equal groups for intragastric administration of NaF (0, 12, 24 and 48 mg/kg body weight/day) for 42 days. Kidneys were taken to measure changes of the cell-cycle at 21 and 42 days of the experiment, using flow cytometry, quantitative real-time polymerase chain reaction (qRT-PCR) and western blot methods. Results: NaF, at more than 12 mg/kg body weight, induced G2/M phase cell-cycle arrest in the renal cells, which was supported by the finding of significantly increased percentages of renal cells in the G2/M phase. We found also that G2/M phase cell-cycle arrest was accompanied by up-regulation of p-ATM, p-Chk2, p-p53, p-Cdc25C, p-CDK1, p21, and Gadd45a protein expression levels; up-regulation of ATM, Chk2, p53, p21, and Gadd45a mRNA expression levels; down-regulation of CyclinB1, mdm2, PCNA protein expression levels; and down-regulation of CyclinB1, CDK1, Cdc25C, mdm2, and PCNA mRNA expression levels. Conclusion: In this mouse model, NaF, at more than 12 mg/ kg, induced G2/M phase cell-cycle arrest by activating the ATM-Chk2-p53/Cdc25C signaling pathway, which inhibits the proliferation of renal cells and development of the kidney. Activation of the ATM-Chk2-p53/Cdc25C signaling pathway is the mechanism of NaF-induced renal G2/M phase cell-cycle arrest in this model. [ABSTRACT FROM AUTHOR]

Fluorine or fluoride can have toxic effects on bone tissue and soft tissue at high concentrations. These negative effects include but not limited to cytotoxicity, immunotoxicity, blood toxicity, and oxidative damage. Apoptosis plays an important role in fluoride-induced toxicity of kidney, liver, spleen, thymus, bursa of Fabricius, cecal tonsil, and cultured cells. Here, apoptosis activated by high level of fluoride has been systematically reviewed, focusing on three pathways: mitochondrion-mediated, endoplasmic reticulum (ER) stress-mediated, and death receptor-mediated pathways. However, very limited reports are focused on the death receptor-mediated apoptosis pathways in the fluoride-induced apoptosis. Therefore, understanding and discovery of more pathways and molecular mechanisms of fluoride-induced apoptosis may contribute to designing measures for preventing fluoride toxicity. [ABSTRACT FROM AUTHOR]

We evaluated the effects of selenium (Se) on antioxidant enzymes of piglet splenic lymphocytes exposed to deoxynivalenol (DON). We measured cell viability, the activities of several antioxidant enzymes, and lactate dehydrogenase (LDH), as well as total antioxidant capacity (T-AOC) and the levels of malonaldehyde (MDA) and hydrogen peroxide (H 2 O 2 ). We found that DON exposure increased the concentrations of LDH, MDA, and H 2 O 2 in all experimental groups in a dose-dependent manner, while the concentrations of other antioxidant enzymes were decreased. In Se-pretreated DON-exposed cells, damage to antioxidant enzymes was reduced, especially in the lower-dose DON groups over longer exposure times. These results may indicate that in piglet splenic lymphocytes, Se can alleviate DON-induced damage to antioxidant enzymes by improving glutathione peroxidase activity. Se may function as a potential antioxidative agent to alleviate DON-induced oxidative stress. [ABSTRACT FROM AUTHOR]

The respiratory system is the primary target of nickel or nickel compound toxicity after inhalation exposure. There are no reports on the effects of nickel or nickel compounds on the lung via dietary administration at present. This study aimed to investigate pulmonary toxicity induced by dietary NiCl2 in broiler chickens by using histopathology, qRT-PCR, and ELISA. In comparison with the control group, NiCl2 intake induced oxidative damage to DNA (upregulation of 8-OHdG) and lipid peroxidation (upregulation of MDA), which was associated with the upregulation of NO and the downregulation of the expression levels and activities of pulmonary CuZn-SOD, Mn-SOD, CAT, GSH-Px, GR and GST mRNA. Also, the T-AOC activity, GSH content, ability to inhibit the generation of hydroxyl radicals, and ratio of GSH/GSSG were decreased in the groups treated with NiCl2. Concurrently, the mRNA expression levels of iNOS, TNF-α, COX-2, IL-1β, IL-6, IL-8, IL-18 and IFN-γ were increased via the activation of NF-κB, and the mRNA expression levels of anti-inflammatory mediators including IL-2, IL-4 and IL-13 were decreased in the groups treated with NiCl2. The above-mentioned results were the first to demonstrate that NiCl2 intake induced pulmonary oxidative stress and inflammatory responses via the dietary pathway, which subsequently contributed to histopathological lesions and dysfunction. [ABSTRACT FROM AUTHOR]

[Display omitted] • High doses of NiCl 2 induces liver damage in mice. • NiCl 2 induces mitochondrial damage in the liver of mice. • NiCl2 induce ferroptosis by inducing mitochondrial damage and down-regulating ferritin. Nickel (Ni) is an environmental toxicant that can cause toxic damage to humans and animals. Although the hepatotoxicity of Ni has been confirmed, its precise mechanism is still unclear. In this study, the results showed that nickel chloride (NiCl 2)-treatment could induce mice hepatotoxicity including hepatic histopathological alterations and up-regulation of serum AST and ALT. According to the results, NiCl 2 increased malondialdehyde (MDA) production while reducing total antioxidant capacity (T-AOC) activity and glutathione (GSH) content. Additionally, NiCl 2 induced mitochondrial damage which was featured by increase in mitochondrial ROS (mt-ROS) and mitochondrial membrane potential (MMP) depolarization. The mitochondrial respiratory chain complexes I-IV and ATP content were decreased in the liver of NiCl 2 -treated mice. Meanwhile, NiCl 2 caused hepatic ferroptosis accompanied by increased iron content in the liver and up-regulation of cyclooxygenase 2 (COX-2) protein and mRNA expression levels, down-regulation of glutathione eroxidase 4 (GPX4), ferritin heavy chain 1 (FTH1) and nuclear receptor coactivator 4 (NCOA4) protein and mRNA expression levels. Altogether, the above mentioned results indicate that NiCl 2 treatment may induce hepatic damage through mitochondrial damage and ferroptosis. [ABSTRACT FROM AUTHOR]

As an extensively environmental pollution, Nickel (Ni) represents a serious hazard to human health. The present study focused on exploring the mechanism of Ni-mediated nephrotoxicity, such as apoptosis, autophagy and oxidative stress. In the current work, NiCl 2 treatment could induce kidney damage. Meanwhile, NiCl 2 treatment elevated ROS production and MDA content and suppressed the antioxidant activity, which was characterized by reducing T-AOC, CAT, SOD activity and GSH content. For investigating the role of oxidative stress on NiCl 2 -mediated nephrotoxicity, N-acetyl cysteine (NAC, effective antioxidant and free radical scavenger) was co-treated with NiCl 2. The results showed that NAC significantly suppressed the NiCl 2 -mediated oxidative stress and mitigated NiCl 2 -induced the kidney damage. Then, whether oxidative stress-induced autophagy and apoptosis were involved in NiCl 2 -induced nephrotoxicity was explored. The findings demonstrated that NAC relieved NiCl 2 -induced autophagy and reversed the activation of Akt/AMPK/mTOR pathway. Concurrently, the results indicated that NAC attenuated NiCl 2 -induced apoptosis, as evidenced by reduction of apoptotic cells and cleaved-caspase-3/− 8/− 9 together with cleaved-PARP protein levels. To sum up, our findings suggested that NiCl 2 -mediated renal injury was associated with oxidative stress-induced apoptosis and autophagy. This study provides new theoretical basis for excess Ni exposure nephrotoxic researches. [Display omitted] • NiCl 2 -treatment could induce oxidative stress, autophagy and apoptosis in the kidney. • Oxidative stress is an essential inducer of NiCl 2 -induced kidney damage. • NiCl 2 induces autophagy through oxidative stress-mediated Akt/AMPK/mTOR pathway. • Oxidative stress play an important role in NiCl 2 -induced apoptosis and autophagy. [ABSTRACT FROM AUTHOR]

This study was performed to investigate the individual and combined toxic effects of deoxynivalenol (DON) and zearalenone (ZEA) on mouse kidney. A total of 360 female mice were divided into nine groups. Each group received intraperitoneal injection of solvent (control), DON, ZEA, or DON + ZEA four times for 12 d. Results showed that ZEA and/or DON increased the apoptosis rate in the kidney, as well as the levels of serum creatinine and blood urea nitrogen. DON and/or ZEA also induced renal oxidative stress as indicated by increased malondialdehyde concentration and nitric oxide level and reduced superoxide dismutase enzyme activity and hydroxyl radical inhibiting capacity. The observed changes were dose and time dependent. This study reports that DON and/or ZEA induced apoptosis, dysfunction, and oxidative stress in mouse kidney. Furthermore, the combination of DON + ZEA exhibited a sub-additive nephrotoxic effect. [ABSTRACT FROM AUTHOR]