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Cadmium (Cd), a heavy metal element, cumulates in the testis and can cause male reproductive toxicity. Although vitamin E (VE) as one of potential antioxidants protects the testis against toxicity of Cd, the underlying mechanism remained uncompleted clear. The aim of this study was to investigate whether the Nrf-2 pathway is involved with the protective effect of VE on testicular damages caused by sub-chronic Cd exposure. Thirty-two SD rats were divided into four groups and orally administrated with VE and/or Cd for 28 consecutive days: control group, VE group (100 mg VE/kg), Cd group (5 mg CdCl2/kg), and VE + Cd group (100 mg VE/kg + 5 mg CdCl2/kg). The results showed that 28-day exposure of Cd caused accumulation of Cd, histopathological lesions, and alternations of sperm parameters (elevated rate of abnormal sperm, decreased count of sperm, declined motility, and viability of sperm). Moreover, the rats exposed to Cd showed significant oxidative stress (increased contents of MDA and decreased levels or activities of T-AOC, GSH, CAT, SOD and GSH-Px) and inhibition of Nrf-2 signaling pathway (downregulation of Nrf-2, HO-1, NQO-1, GCLC, GCLM and GST) of the testes. In contrast, VE treatment significantly reduced the Cd accumulation, alleviated histopathological lesions and dysfunctions, activated Nrf-2 pathway, and attenuated the oxidative stress caused by Cd in the testes of rats. In conclusion, VE, through upregulating Nrf-2 pathway, could protect testis against oxidative damages induced by sub-chronic Cd exposure.

Cadmium (Cd), a widely distributed heavy metal, is extremely toxic to the kidney. Vitamin E (VE) is an important antioxidant in the body. It is known that VE exerts a protective effect on renal oxidative damage caused by Cd, but the effect and mechanism of VE on apoptosis are not fully understood. Thus, we conducted this study to explore the protective effect of VE on Cd-induced renal apoptosis and to elucidate its potential mechanism. Thirty-two 9-week-old male Sprague-Dawley rats were randomly divided into four groups, namely control, VE (100 mg/kg VE), Cd (5 mg/kg CdCl2), and VE + Cd (100 mg/kg VE + 5 mg/kg CdCl2), and received intragastric administration of Cd and/or VE for 4 weeks. The results showed that Cd exposure significantly reduced the weight of the body and kidney, elevated the accumulation of Cd in the kidney as well as the levels of BUN and Scr in serum, caused renal histological alterations, decreased the GSH and T-AOC contents and antioxidant enzyme (SOD, CAT, GSH-PX) activities, and increased renal MDA content. And the increased number of TUNEL-positive cells by Cd was accompanied by upregulated mRNA and protein expressions of apoptotic regulatory molecules (Bax, Caspase-3, GRP94, GRP78, Caspase-8) and downregulated Bcl-2 expressions. However, the combined treatment of Cd and VE could restore the above parameters to be close to those in the control rats. In conclusion, VE supplement could alleviate Cd-induced rat renal damage and oxidative stress through enhancing the antioxidant defense system and inhibiting apoptosis of renal cells.

Early-life exposure to environmental cadmium (Cd) is known to cause developmental disorders, yet the effect and mechanism of gestational exposure to Cd on the offspring's cognitive function remains unclear. Placenta as a well-established target organ for Cd-impaired fetal development, its role in estrogen regulation and offspring cognitive function is unknown. Our in vivo experiments found that gestational Cd exposure impaired cognitive function in adult male offspring, accompanied with lowered 17β-estradiol (E2) level in the male fetal brain upon Cd exposure. Correspondingly, the expression of synapse-associated proteins including brain-derived neurotrophic factor (BDNF), post-synaptic density protein 95 (PSD95) and synapsin-1 were downregulated, which were reversed when supplemented with E2 hormone during gestation. Further observation showed placental estrogen synthesis inhibition and general control non-derepressible 2 (GCN2) signaling activation upon Cd exposure, whereas placental estrogen synthesis could be restored through inhibiting GCN2 activity. Based on ovariectomy (OVX) of pregnant mice, we confirmed that Cd exposure reduced E2 level in fetal brain via inhibiting placenta-derived estrogen synthesis. The aforementioned Cd-induced fetal brain injury and cognitive impairment in adult offspring were significantly alleviated when pregnant dams were supplemented with anti-stress agent N-Acetyl-l-cysteine. In summary, Cd disrupted placenta-derived estrogen synthesis via activating GCN2 signaling, and thereby caused cognitive impairment in adult offspring mice. Our findings suggest that placenta-derived estrogen may be an effect marker of environmental toxicants-evoked cognitive dysfunction in adult offspring and suggest that environmental toxicants may affect the fetal brain development via placenta-fetal-brain axis.

Enhanced electrokinetic remediation (EKR) allows the rapid remediation of heavy metal-contaminated clay, but the impacts of this process on soil micro-ecology have rarely been evaluated. In this study, nitric acid, acetic acid, and EDTA were applied for enhancement of EKR and the effects on Cd removal, soil enzyme activity, and soil bacterial communities (SBCs) were determined. Nitric acid and acetic acid allowed 93.2% and 91.8% Cd removal, respectively, and EDTA treatment resulted in 40.4% removal due to the formation of negatively charged EDTA-Cd complexes, resulting in opposing directions of Cd electromigration and electroosmosis flow and slow electromigration rate caused by low voltage drop. Activities of soil beta-glucosidase, acid phosphatase, and urease, were all reduced by enhanced EKR treatment, especially nitric acid treatment, by 46.2%, 58.8% and 57.7%, respectively. The SBCs were analyzed by high-throughput sequencing and revealed significantly increased diversity for acetic acid treatment, no effect for EDTA treatment, and reduced diversity for nitric acid treatment. Compared with nitric acid and EDTA, acetic acid treatment enhanced EKR for higher Cd removal and improved biodiversity.

Background: Environmental cadmium, with a high average dietary intake, is a severe public health risk. However, the long-term health implications of environmental exposure to cadmium in different life stages remain unclear. Objectives: We investigated the effects of early exposure to cadmium, at an environmentally relevant dosage, on adult metabolism and the mechanism of action. Methods: We established mouse models with low-dose cadmium (LDC) exposure in early life to examine the long-term metabolic consequences. Intestinal flora measurement by 16S rDNA sequencing, microbial ecological analyses, and fecal microbiota transplant was conducted to explore the potential underlying mechanisms. Results: Early LDC exposure (100 nM) led to fat accumulation in adult male mice. Hepatic genes profiling revealed that fatty acid and lipid metabolic processes were elevated. Gut microbiota were perturbed by LDC to cause diversity reduction and compositional alteration. Time-series studies indicated that the gut flora at early-life stages, especially at 8 weeks, were vulnerable to LDC and that an alteration during this period could contribute to the adult adiposity, even if the microbiota recovered later. The importance of intestinal bacteria in LDC-induced fat accumulation was further confirmed through microbiota transplantation and removal experiments. Moreover, the metabolic effects of LDC were observed only in male, but not female, mice. Conclusions: An environmental dose of cadmium at early stages of life causes gut microbiota alterations, accelerates hepatic lipid metabolism, and leads to life-long metabolic consequences in a sex-dependent manner. These findings provide a better understanding of the health risk of cadmium in the environment. Citation: Ba Q, Li M, Chen P, Huang C, Duan X, Lu L, Li J, Chu R, Xie D, Song H, Wu Y, Ying H, Jia X, Wang H. 2017. Sex-dependent effects of cadmium exposure in early life on gut microbiota and fat accumulation in mice. Environ Health Perspect 125:437–446; http://dx.doi.org/10.1289/EHP360

We studied the effects of three organic acids (citric acid, tartaric acid and malic acid) on the biomass, photosynthetic pigment content and photosynthetic parameters of Salix variegata under Cd stress and observed the ultrastructure of mesophyll cells in each treatment. Cd stress significantly reduced photosynthesis by reducing the content of pigments and disrupting chloroplast structure, which consequently decreased the biomass. However, respective addition of three organic acids greatly increased the biomass of S. variegata under Cd stress. Among them, the effect of malic acid or tartaric acid on shoot and total biomass accumulation was greater than that of citric acid. The alleviation of biomass probably related with the photosynthetic process. Results revealed that treatment with each organic acid enhanced the net photosynthesis rate under Cd stress. Malic acid promoted plant growth and biomass by increasing the chlorophyll content and mitigating damage to the photosynthetic apparatus resulting from Cd stress. Tartaric acid had little impact on the photosynthetic pigment content, but it was important in mitigating the ultrastructural damage of plants caused by Cd. Addition of citric acid significantly increased the carotenoid as well as the number and volume of chloroplasts in mesophyll cells, while the mitigation of structural damage in the photosynthetic apparatus was weaker than that in tartaric acid or malic acid treatment. It is concluded that application of tartaric acid or malic acid is effective in increasing the growth potential of S. variegata under Cd stress and thus can be a promising approach for the phytoremediation of Cd-contaminated soil.

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 CdCl2) and VE+Cd (100 mg/kg VE+5 mg/kg CdCl2), 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.

Four complexes, [Cu4L2(OCH3)2(CH3OH)2]&middot, 2H2O (1), [Zn2L2Cl4]&middot, 2H2O&middot, 2CH3OH (2), [Hg2L2Br4]&middot, 4CH3OH (3), and {[CdL2Cl2]&middot, 4H2O&middot, 4CH3OH}n (4), have been synthesized and characterized from a bis(pyridylhydrazone) ligand (L) with copper(II), zinc(II), mercury(II) or cadmium(II), respectively. Complex 1 exists as a centrosymmetric tetranuclear dimer with L as deprotonated tridentate ligand. Complexes 2 and 3 exist as centrosymmetric metallamacrocycles with L as bidentate ligand. Complex 4 exists as a 1D looped-chain coordination polymer. The thermal stabilities and vapor adsorption properties of the four complexes were investigated as well.

Exposure of Phanerochaete chrysosporium ( P. chrysosporium ) to heavy metals is a common phenomenon due to their environmental applications. In the present study, P. chrysosporium accumulated high intracellular contents of Cd when cultured in metal-enriched culture medium, and then built up of distinct inhibition of growth rate. Concomitantly, rapid accumulation of H 2 O 2 occurred and then triggered an induced signal transduction in activation of non-enzymatic antioxidants (glutathione (GSH), ascorbate (Asc) and phenolics) (below 30 μmol g −1 , R 2 > 0.6). Promoted yield of antioxidants (GSH, Asc and phenolics) was observed in Cd-exposed P. chrysosporium , and a tight network of cooperation of those tested antioxidants was innovatively affirmed via Pearson correlation analysis ( p

Heavy metal contamination in environment and food has attracted intensive attention from the public since it poses serious threats to ecological system and human health. Traditional detection methods for heavy metals such as atomic absorption spectrometry have a fairly low detection limit, but the methods have many limitations and disadvantages. Therefore, it is of significance to develop a rapid technology for real-time and online detection of heavy metals. The electrochemical aptasensor-based technology is promising in the detection of heavy metals with advantages of high sensitivity, specificity, and accuracy. Although its development is rapid, more researches should be carried out before this technology can be used for on-site detection. In this review, the origin, basic principles and development of electrochemical aptasensors are introduced. The applications of nanomaterials and electrochemical aptasensors for the detection of heavy metals (mainly mercury, lead, cadmium, and arsenic) are summarized. The research and application tendency of electrochemical aptasensors for detection of heavy metals are prospected.

Phosphate (P) compounds are usually used as chemical amendment for in situ remediation of heavy metal polluted sediment. However, the low deliverability, weak utilization and potential risk of eutrophication inhibit the application of most P materials. Therefore, rhamnolipid (Rha), a kind of anionic biosurfactant which has algicidal activity, was employed in this study to synthesize a new kind of nano-chlorapatite (nClAP) for Pb and Cd immobilization. Characterization results showed that the Rha stablized nClAP (Rha-nClAP) was uniformly distributed in suspensions within about 5nm. Experimental data demonstrated that the combination of Rha and nClAP could greatly enhance the Pb- and Cd-immobilization efficiencies, promoting their transformation from labile fractions to stable fractions through precipitation or adsorption processes, especially when the Rha approached to its critical micelle concentration. And Rha-nClAP could also decrease both the TCLP-leachable Pb and Cd with maximum reduction efficiencies of 98.12% and 96.24%, respectively, which also presented concentration dependence of Rha. Changes of available phosphorus implied the dissolution of nClAP during the treatment and the detection of organic matter demonstrated that the microorganisms may involve in the remediation.

This study examines the role of oxalic acid in the uptake of Cd and participation in detoxification process in Phanerochaete chrysosporium. Cd-induced oxalic acid secretion was observed with growth inhibition and enzyme inactivation (LiP and MnP) of P. chrysosporium. The peak value of oxalic acid concentration was 16.6 mM at initial Cd concentration of 100 mg L−1. During the short-term uptake experiments, the uptake of Cd was enhanced and accelerated in the presence of oxalic acid and resulted in alleviated growth and enzyme inhibition ratios. The formation of a metal-oxalate complex therefore may provide a detoxification mechanism via effect on metal bioavailability, whereby many fungi can survive and grow in environments containing high concentrations of toxic metals. The present findings will advance the understanding of fungal resistance to metal stress, which could show promise for a more useful application of microbial technology in the treatment of metal-polluted waste.

The accumulation of cadmium and lead in rice (Oryza sativa L.) grains is a potential threat to human health. In this study, the effect of selenium fertilization on the uptake and translocation of cadmium and lead in rice plants was investigated. Rice plants were cultivated using cadmium and lead contaminated soils with selenium addition at three concentrations (0, 0.5 and 1 mg kg−1). At maturity, plants were harvested, and element concentrations in rice tissues were analyzed by using ICP-MS. Selenium application significantly increased selenium accumulation in rice grain, and markedly decreased cadmium and lead concentrations in rice tissues. In brown rice grains, selenium application reduced cadmium concentrations by 44.4 %, but had no significant effect on lead accumulation. Selenium application significantly decreased metal mobility in soils, at 0.5 mg kg−1 treatment, the translocation factor of cadmium and lead from soil to iron plaque decreased by 71 and 33 % respectively. The mechanism of selenium mitigating of heavy metal accumulation in rice could be decreasing metal bioavailability in soil. Selenium fertilization could be an effective and feasible method to enrich selenium and reduce cadmium levels in brown rice.

The present study was performed to determine the effects of single and combined exposure of copper (Cu) and cadmium (Cd) on lipogenic metabolism and metal element composition of javelin goby Synechogobius hasta. Two hundred and forty uniform-sized S. hasta (initial mean weight 20.3 ± 0.3 g [mean ± SEM throughout]; initial body length 15.2 ± 0.2 cm) were randomly assigned to 12 fiberglass tanks (water volume 300 l) with 20 fish/tank. The fish were exposed to four treatments with different Cu and Cd concentration for 30 days, respectively: (1) control (without extra Cu and Cd addition), (2) Cu (nominal concentrations of 77 μg/l), (3) Cd (79 μg/l), and (4) Cu + Cd (Cu/Cd coexposure). Growth decreased, but hepatosomatic index, viscerosomatic index, and lipid content increased after metal exposure. Staining with Oil Red O and haematoxylin and eosin showed extensive alterations in liver of metals-exposed fish. Metal exposure influenced the accumulation of metal elements (Cu, Cd, iron, zinc, and manganese) in several tissues (muscle, gill, intestine, liver, and spleen) and increased hepatic 6-phosphogluconate dehydrogenase, glucose-6-phosphate dehydrogenase, malic enzyme, isocitrate dehydrogenase, and fatty acid synthase activities. The results of the present study indicated that the changes in lipogenic metabolism and metal element compositions of fish under Cu and Cd coexposure could not be explained by synergism of the addition of the effects observed in singly Cu- or Cd-exposed fish. To our knowledge the present study, for the first time, investigated the effects of Cu and Cd coexposure on hepatic lipogenic metabolism and metal element compositions in a wide range of tissues and organs in fish, which provided new evidence for Cu and Cd interactions in fish.

This paper investigated how sodium alginate (SA)-modified nanoscale zero-valent iron (NZVI), play a constructive role in the remediation of cadmium (Cd) contaminated river sediments. The changes of the fraction of Cd, enzyme activities (urease, catalase, dehydrogenase) and bacterial community structures with the treatment by SNZVI were observed. The sequential extraction experiments demonstrated that most mobile fractions of Cd were transformed into residues (the maximum residual percentage of Cd increases from 15.49% to 57.28% after 30 days of incubation at 0.1 wt% SA), with the decrease of bioavailability of Cd. Exclusive of dehydrogenase, the activities of the other two enzymes tested were enhanced with the increase of incubation time, which indicated that dehydrogenase might be inhibited by ferric ions formed from SNZVI whereas no obvious inhibition was found for other enzymes. Polymerase chain reaction denaturing gradient gel electrophoresis (PCR-DGGE) analyses were used for the detection of microbial community changes, and the results showed that SNZVI and NZVI could increase bacterial taxa and improve bacterial abundance. All the experimental findings of this study provide new insights into the potential consequences of SNZVI treatments on the metal Cd immobilization in contaminated river sediments.

Cadmium has been defined as type I carcinogen for humans, but the underlying mechanisms of its carcinogenic activity and its influence on protein-protein interactions in cells are not fully elucidated. The aim of the current study was to evaluate, systematically, the carcinogenic activity of cadmium with systems biology approaches. From a literature search of 209 studies that performed with cellular models, 208 proteins influenced by cadmium exposure were identified. All of these were assessed by Western blotting and were recognized as key nodes in network analyses. The protein-protein functional interaction networks were constructed with NetBox software and visualized with Cytoscape software. These cadmium-rewired genes were used to construct a scale-free, highly connected biological protein interaction network with 850 nodes and 8770 edges. Of the network, nine key modules were identified and 60 key signaling pathways, including the estrogen, RAS, PI3K-Akt, NF-κB, HIF-1α, Jak-STAT, and TGF-β signaling pathways, were significantly enriched. With breast cancer, colorectal and prostate cancer cellular models, we validated the key node genes in the network that had been previously reported or inferred form the network by Western blotting methods, including STAT3, JNK, p38, SMAD2/3, P65, AKT1, and HIF-1α. These results suggested the established network was robust and provided a systematic view of the carcinogenic activities of cadmium in human.

Phanerochaete chrysosporium are known to be vital hyperaccumulation species for heavy metal removal with admirable intracellular bioaccumulation capacity. This study analyzes the heavy metal-induced glutathione (GSH) accumulation and the regulation at the intracellular heavy metal level in P. chrysosporium. P. chrysosporium accumulated high levels of GSH, accompanied with high intracellular concentrations of Pb and Cd. Pb bioaccumulation lead to a narrow range of fluctuation in GSH accumulation (0.72-0.84 μmol), while GSH plummeted under Cd exposure at the maximum value of 0.37 μmol. Good correlations between time-course GSH depletion and Cd bioaccumulation were determined (R (2) > 0.87), while no significant correlations have been found between GSH variation and Pb bioaccumulation (R (2) < 0.38). Significantly, concentration-dependent molar ratios of Pb/GSH ranging from 0.10 to 0.18 were observed, while molar ratios of Cd/GSH were at the scope of 1.53-3.32, confirming the dominant role of GSH in Cd chelation. The study also demonstrated that P. chrysosporium showed considerable hypertolerance to Pb ions, accompanied with demand-driven stimulation in GSH synthesis and unconspicuous generation of reactive oxygen stress. GSH plummeted dramatically response to Cd exposure, due to the strong affinity of GSH to Cd and the involvement of GSH in Cd detoxification mechanism mainly as Cd chelators. Investigations into GSH metabolism and its role in ameliorating metal toxicity can offer important information on the application of the microorganism for wastewater treatment.