Acute Cadmium Exposure Research Articles

Circadian time-dependent antioxidant and inflammatory responses to acute cadmium exposure in the brain of zebrafish

Up to date, little information is available on effects of circadian rhythm on metal-induced toxicity in fish. In this study, zebrafish were acutely exposed to 0.97mgL−1 cadmium for 12h either at ZT0 (the light intensity began to reached maximum) or at ZT12 (light intensity began to reached minimum) to evaluate the temporal sensitivity of oxidative stress and inflammatory responses in the brain of zebrafish. Profiles of responses of some genes at mRNA, protein and activity levels were different between ZT0 and ZT12 in the normal water. Exposure to Cd induced contrary antioxidant responses and similar inflammatory responses between ZT0 and ZT12. However, the number of inflammatory genes which were up-regulated was significantly greater at ZT12 than at ZT0. And, the up-regulated inflammatory genes were more responsive at ZT12 than at ZT0. At ZT12, antioxidant genes were down-regulated at mRNA, protein and activity levels. Contrarily, antioxidant genes were not affected at mRNA levels but activated at the protein and/or activity levels at ZT0. Reactive oxygen species (ROS) sharply increased and remained relatively stable when fish were exposed to Cd at ZT12 and ZT0, respectively. Positive correlations between ROS levels and mRNA levels of nuclear transcription factor κB (NF-κB) and between mRNA levels of NF-κB and its target genes were observed, suggesting that ROS may play an essential role in regulating the magnitude of inflammatory responses. Taken together, oxidative stress and immunotoxicity in the brain were more serious when fish were exposed to Cd in the evening than in the morning, highlighting the importance of circadian rhythm in Cd-induced neurotoxicity in fish.

RNA‐Seq identifies redox balance related gene expression alterations under acute cadmium exposure in yeast

The nonessential metal cadmium can cause cell toxicity and is associated with a range of human diseases including cardiovascular diseases, neurodegenerative diseases and cancers. In this study, cadmium-induced global gene expression profile of yeast was obtained using RNA Sequencing (RNA-Seq) and further analyzed by means of informatics and experiments. A total of 912 Differentially Expressed Genes (DEGs) (FDR of q < 0.01), including 415 Cd-inducible and 497 Cd-repressed genes were identified. Based on the DEGs, 25 cadmium responsive Clusters of Orthologous Group (COG) and three types of cadmium-induced Gene Ontology (GO) including cellular components, molecular functions and biological processes were analyzed in details. Thereafter, 79 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways under cadmium exposure were assigned. Collectively, 108 redox balance related genes were extracted under cadmium exposure. Meanwhile, cadmium exposure lowered cellular Mitochondrial Membrane Potential (MMP) and increased Reactive Oxygen Species (ROS) levels significantly in the context of mitochondrial dysfunction. Furthermore, cadmium exposure increased cellular GSH levels and decreased GSSG levels and also lowered GSSG/GSH ratio of cells, which supports experimentally our claim that the redox balance is the primary mechanism for cadmium toxicity. The results present in this study may provide new strategies for cadmium detoxification and prevention or therapies of cadmium-associated diseases.

Alteration of mitochondrial phospholipid due to the PLA2 activation in rat brains under cadmium toxicity.

Cadmium (Cd) is a heavy metal that has received considerable environmental and occupational concern. Cd causes toxic effects due to its accumulation in a variety of tissues, including the kidney, liver and the nervous system (CNS); however, the exact mechanism is poorly understood. In the present study, we tried to explore the impact of acute cadmium exposure on rat brain phospholipids (PLs). Cd exposure significantly reduced PLs in a time dependent manner and the reduction was due to the activation of the Phospholipase A2 enzymes (sPLA2, cPLA2). The release of arachidonic acid from PLs increased during inflammatory conditions by PLA2s. The mRNA expression of cyclooxygenase2 (COX2) and subsequently the pro-inflammatory cytokines, namely, Interleukin 1 (IL-1) and IL-6, were up regulated; however, the expression of anti-inflammatory cytokine IL-10 was reduced in a time dependent manner. The expression of the Tumor necrosis factor alpha (TNF-α), Inducible nitric oxide synthase (iNOS) and Interferon gamma (INF-γ) also experienced increases in the expression. Likewise the mRNA expression of the pro-apoptotic factor, Bcl-2-associated X protein (Bax), was elevated, whereas anti-apoptosis B-cell lymphoma 2 (Bcl2) was down regulated. This present study might help to decipher the effects of cadmium toxicity on rat brain.

The Protective Effects of Melatonin Against Oxidative Stress and Inflammation Induced by Acute Cadmium Exposure in Mice Testis.

Cadmium (Cd) is widely used in daily life and was recently recognized as a possible source of human toxicity due to its ability to accumulate in organs. Previous studies have shown that Cd exposure may cause testicular toxicity through oxidative stress and an inflammatory effect. Melatonin has been demonstrated to be an effective anti-oxidant and has an anti-inflammatory effect. The aim of the present study was to investigate the toxicological effects of Cd on reproduction in male mice and the potential protective action of melatonin against these adverse effects. Adult male mice were injected intraperitoneally with Cd at a dose of 2mg/kg body weight per day for seven consecutive days with or without melatonin pretreatment. Sex organ weight, sperm parameters including sperm quality, apoptosis, acrosome integrity, mitochondrial membrane potential, testicular morphology, serum sex hormone, inflammatory status, and oxidative stress were evaluated. The results showed that significant adverse effects were observed in the male reproductive system after Cd exposure, including alterations in sperm parameters, increased DNA damage, and sex hormone disturbance. Acute Cd exposure also significantly increased malondialdehyde (MDA) contents, decreased glutathione (GSH) and superoxide dismutase (SOD) activities, and upregulated levels of the pro-inflammatory cytokines, tumor necrosis factor-alpha (TNF-α), and interleukin-1beta (IL-1β), in the testis. In contrast, melatonin pretreatment significantly alleviated these toxic effects, and its mechanism may involve inhibiting MDA level, restoring GSH and SOD activities, and reducing the upregulation of TNF-α and IL-1β. Our data suggest that oxidative stress and inflammation are involved in Cd-induced toxicity in the male reproductive system and that co-administration of melatonin exerts a protective effect against Cd-induced male reproductive toxicity.

Temporal changes in rat liver gene expression after acute cadmium and chromium exposure.

U.S. Service Members and civilians are at risk of exposure to a variety of environmental health hazards throughout their normal duty activities and in industrial occupations. Metals are widely used in large quantities in a number of industrial processes and are a common environmental toxicant, which increases the possibility of being exposed at toxic levels. While metal toxicity has been widely studied, the exact mechanisms of toxicity remain unclear. In order to further elucidate these mechanisms and identify candidate biomarkers, rats were exposed via a single intraperitoneal injection to three concentrations of CdCl2 and Na2Cr2O7, with livers harvested at 1, 3, or 7 days after exposure. Cd and Cr accumulated in the liver at 1 day post exposure. Cd levels remained elevated over the length of the experiment, while Cr levels declined. Metal exposures induced ROS, including hydroxyl radical (•OH), resulting in DNA strand breaks and lipid peroxidation. Interestingly, ROS and cellular damage appeared to increase with time post-exposure in both metals, despite declines in Cr levels. Differentially expressed genes were identified via microarray analysis. Both metals perturbed gene expression in pathways related to oxidative stress, metabolism, DNA damage, cell cycle, and inflammatory response. This work provides insight into the temporal effects and mechanistic pathways involved in acute metal intoxication, leading to the identification of candidate biomarkers.

Acute Cadmium Exposure Reduces the Local Angiotensin I Converting Enzyme Activity and Increases the Tissue Metal Content.

Cadmium exposure causes health problems that may result from increased oxidative stress and from changes in enzyme metalloproteases activities as angiotensin-converting enzyme (ACE). In fact, cadmium produces inhibition of serum ACE but is not known how cadmium acts on tissue ACE activity and whether following acute exposure tissue cadmium content is increased. In order to elucidate these issues, a cadmium bolus was injected intravenously in Wistar rats, and the cadmium content and the ACE activity were measured in the serum, lungs, aorta and kidneys. Moreover, in order to clarify if the cadmium affects directly tissue ACE activity, acute metal exposure in vitro was performed. Our results demonstrated that 120min following cadmium administration, blood and organ cadmium content were both increased. Serum and lung ACE activity were reduced following acute cadmium exposure, but aortic and kidney ACE activities were not affected. The inhibitory effects induced by cadmium on ACE activity were also observed in the serum, as well as the lungs and the aorta, but not in the kidneys following in vitro exposure. Moreover, the inhibitory effects induced by cadmium on ACE activity were partially restored in vitro by zinc supplementation, suggesting a possible interaction or competition between cadmium and zinc by at the active site of ACE. Summarising, our results suggest that acute cadmium exposure promotes an increase in the tissue metal content that was accompanied by direct inhibition of serum, aorta and lung ACE activity, an effect that is cadmium concentration-dependent and is partially reversed by zinc.

Gene networks and toxicity pathways induced by acute cadmium exposure in adult largemouth bass (Micropterus salmoides)

Cadmium is a heavy metal that can accumulate to toxic levels in the environment leading to detrimental effects in animals and humans including kidney, liver and lung injuries. Using a transcriptomics approach, genes and cellular pathways affected by a low dose of cadmium were investigated. Adult largemouth bass were intraperitoneally injected with 20μg/kg of cadmium chloride (mean exposure level – 2.6μg of cadmium per fish) and microarray analyses were conducted in the liver and testis 48h after injection. Transcriptomic profiles identified in response to cadmium exposure were tissue-specific with the most differential expression changes found in the liver tissues, which also contained much higher levels of cadmium than the testis. Acute exposure to a low dose of cadmium induced oxidative stress response and oxidative damage pathways in the liver. The mRNA levels of antioxidants such as catalase increased and numerous transcripts related to DNA damage and DNA repair were significantly altered. Hepatic mRNA levels of metallothionein, a molecular marker of metal exposure, did not increase significantly after 48h exposure. Carbohydrate metabolic pathways were also disrupted with hepatic transcripts such as UDP-glucose, pyrophosphorylase 2, and sorbitol dehydrogenase highly induced. Both tissues exhibited a disruption of steroid signaling pathways. In the testis, estrogen receptor beta and transcripts linked to cholesterol metabolism were suppressed. On the contrary, genes involved in cholesterol metabolism were highly increased in the liver including genes encoding for the rate limiting steroidogenic acute regulatory protein and the catalytic enzyme 7-dehydrocholesterol reductase. Integration of the transcriptomic data using functional enrichment analyses revealed a number of enriched gene networks associated with previously reported adverse outcomes of cadmium exposure such as liver toxicity and impaired reproduction.

Catalase Activity in Brown Mussels (Perna perna) under Acute Cadmium, Lead, and Copper Exposure and Depuration Tests

Brown mussels (Perna perna) were exposed to cadmium (Cd), lead (Pb), and copper (Cu) concentrations under acute exposure and exposure-depuration tests for the estimation of biochemical biomarker catalase (CAT). The acute tests showed accumulated Cd, Pb, and Cu inPerna pernacorrelated linearly with the exposure concentrations (R2=0.794,R2=0.891, andR2=0.985for Cd, Pb, and Cu, resp.). The results of CAT increased significantly in tissues of treatment mussels after 72 h exposure when compared to control. The values of total protein were disturbed in exposed groups when compared with control. These results suggest that metabolites and catalase activity were affected by heavy metal exposures. Analysis using the Spearman rank correlation coefficient showed that the CAT activity appeared to have a significant positive correlativity (Rs=0.921,Rs=0.949, andRs=0.949for Cd, Pb, and Cu, resp.) with the accumulated Cd, Pb, and Cu concentrations, respectively. The result of exposure-depuration tests showed that there is a general tendency for CAT to decrease in depuration phase, suggesting that the induction of catalase is metal and/or mixture of metals dependent.

P53 is involved in shrimp survival via its regulation roles on MnSOD and GPx in response to acute environmental stresses

The tumor suppressor gene p53 plays a critical role in safeguarding the integrity of genome in mammalian cells. It acts as a sequence-specific transcription factor. Once activated by a variety of cellular stresses, p53 transactivates downstream target genes, through which it regulates cell cycle and apoptosis. However, little is known about p53 as well as its downstream target genes in invertebrates. A full length cDNA that encodes a 453-amino-acid p53 protein (Lvp53) was characterized in the Pacific white shrimp (Litopenaeus vannamei) to explore the potential relationships between p53 and two antioxidant enzyme genes: Mn-superoxide dismutase (MnSOD) and glutathione peroxidase (GPx) in eliminating cell stresses in L. vannamei. Sequence analysis revealed a close phylogenetic relationship between Lvp53 and that of Marsupenaeus japonicus, and a high degree of conservation in critical amino acids residues is involved in DNA and zinc binding among species. Quantitative real-time PCR showed that Lvp53 was expressed with varied levels in all the 11 tissues under investigation. In response to acute pH challenge, the relative expression of Lvp53 was induced in a pH- and time-dependent manner, with the peak observed at pH6.1 and after 24h of treatment, in which condition, both the relative mRNA expressions and the enzymatic activities of LvMnSOD and LvGPx were increased correspondingly. In response to acute cadmium (Cd) exposure, the relative expression of Lvp53 was upregulated in a time- and concentration-dependent manner, with the maximum detected at Cd 6.6μM and after 48h of exposure, in which case, both the transcripts and the enzymatic activities of LvMnSOD and LvGPx were also induced. After Lvp53 transcripts were declined by double-strand RNA injection, the relative mRNA expressions of LvMnSOD and LvGPx were decreased correspondingly. Meanwhile, pH6.1 or 6.6μM Cd could not induce the transcripts or the enzymatic activities of LvMnSOD or LvGPx any more in Lvp53-silenced shrimp, but increased shrimp mortalities. These results indicated the involvement of Lvp53, LvMnSOD and LvGPx in mediating cell stress caused by suboptimal pH and elevated levels of Cd in L. vannamei, and that the expressions of LvMnSOD and LvGPx were positively regulated by Lvp53, which is a potential mechanism for shrimp to survive the oxidative stress that occurs during short-term exposure to Cd or challenge with acidic pH. This finding will contribute to better understanding of p53 signaling pathways and redox regulation in invertebrate organisms.

Chronic Cadmium Exposure Stimulates SDF-1 Expression in an ERα Dependent Manner

Cadmium is an omnipotent environmental contaminant associated with the development of breast cancer. Studies suggest that cadmium functions as an endocrine disruptor, mimicking the actions of estrogen in breast cancer cells and activating the receptor to promote cell growth. Although acute cadmium exposure is known to promote estrogen receptor-mediated gene expression associated with growth, the consequence of chronic cadmium exposure is unclear. Since heavy metals are known to bioaccumulate, it is necessary to understand the effects of prolonged cadmium exposure. This study aims to investigate the effects of chronic cadmium exposure on breast cancer progression. A MCF7 breast cancer cell line chronically exposed to 10−7 M CdCl2 serves as our model system. Data suggest that prolonged cadmium exposures result in the development of more aggressive cancer phenotypes – increased cell growth, migration and invasion. The results from this study show for the first time that chronic cadmium exposure stimulates the expression of SDF-1 by altering the molecular interactions between ERα, c-jun and c-fos. This study provides a mechanistic link between chronic cadmium exposure and ERα and demonstrates that prolonged, low-level cadmium exposure contributes to breast cancer progression.

Cadmium exposure induces vascular injury due to endothelial oxidative stress: the role of local angiotensin II and COX-2

Cadmium is an environmental pollutant that is closely linked with cardiovascular diseases, such as atherosclerosis and hypertension. Moreover, cadmium can induce an increase in oxidative stress. One of the main sites affected by oxidative stress is the aorta, which consequently develops atherosclerosis. However, there are few reports demonstrating aortic effects induced by small concentrations of cadmium that are similar to those found in the blood resulting from occupational exposure. Furthermore, several studies have reported on chronic cadmium exposure, and the results of these studies may have been influenced by the secondary effects induced by this metal, such as hypertension. Therefore, we investigated the effects of acute cadmium exposure on the vascular reactivity to phenylephrine of aortic rings isolated from male Wistar rats. Cadmium increased phenylephrine reactivity without changing the vasorelaxation induced by acetylcholine and sodium nitroprusside. Endothelial damage or incubation with L-NAME shifted the phenylephrine concentration–response curves leftward in arteries incubated with or without cadmium, but the curves were shifted to a lesser degree after cadmium incubation. Enalapril, losartan, the nonselective COX inhibitor indomethacin, the TXA(2) synthase inhibitor furegrelate, the selective COX-2 inhibitor NS 398, the TP receptor antagonist SQ 29.548, the EP1 receptor antagonist SC 19.220, superoxide dismutase, and the NADPH oxidase inhibitor apocynin partially reverted the cadmium-induced effects on the reactivity to phenylephrine. Cadmium exposure increased vasoconstrictor activity by reducing NO bioavailability owing to the increased production of ROS by NADPH oxidase. The results of the tested cadmium concentration, which is below the reference values, suggest that acute cadmium exposure may induce vascular injury through endothelial oxidative stress. These data contribute to the evidence indicating that cadmium is a high risk to public health.

γ-Oryzanol protects against acute cadmium-induced oxidative damage in mice testes

Cadmium is a non-essential heavy metal that is present at low levels mainly in food and water and also in cigar smoke. The present study evaluated the testicular damage caused by acute cadmium exposure and verified the protective role of γ-oryzanol (ORY). Mice were administrated with a single dose of 2.5mg/kg of CdCl2, and then treated with ORY (50mM in canola oil, 5mL/kg). Testes were removed after 24h and tested for lipid peroxidation (TBARS), protein carbonylation, DNA breakage, ascorbic acid, cadmium and non-proteic thiols contents, and for the activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione S-transferase (GST) and δ-aminolevulic acid dehydratase (δ-ALA-D). Cadmium presented a significant alteration in all parameters, except GPx and CAT activities. Therapy reduced in a slight degree cadmium concentration in testes (around 23%). ORY restored SOD and GST activities as well as TBARS production to the control levels. Furthermore, ORY partially recovered δ-ALA-D activity inhibited by cadmium. This study provides the first evidence on the therapeutic properties of ORY in protecting against cadmium-induced testicular toxicity.

Catechins are not major components responsible for the beneficial effect of Camellia sinensis on the ovarian δ-ALA-D activity inhibited by cadmium

Cadmium has been associated with a wide spectrum of deleterious effects on the reproductive tissues, including ovary. This investigation evaluated the protective role of Camellia sinensis (green, white and red teas) in the cadmium-induced inhibition of ovarian δ-aminolevulinate dehydratase (δ-ALA-D) activity in vitro and ex vivo. This study demonstrated that green and white teas restored the cow ovary δ-ALA-D activity inhibited by cadmium whereas red tea had no effect in vitro. In addition, green tea was able to restore enzyme activity inhibited after acute cadmium exposure in mice ovary. Teas infusions composition was assessed by HPLC in a quantitative assay for catechins, purine alkaloids and gallic acid as well as total polyphenol content. The greatest effect of green tea observed in vitro as well as the protective role presented in the ex vivo study could be attributed to the major content of phenols, but not catechins. In fact, catechins were not able to restore enzyme activity inhibited by cadmium, demonstrating that these compounds are not major components responsible for the beneficial effect of green tea observed in this study. This study demonstrated the helpful effect of green tea infusion in ameliorating a marker protein of cadmium intoxication in ovarian tissue.

Acute cadmium exposure augments MMP-9 secretion and disturbs MMP-9/TIMP-1 balance

Background: Cadmium (Cd) is an extremely toxic metal commonly found in industrial work places, a food contaminant and a major component of cigarette smoke. Tobacco smoke and Cd inhalation result in alveolar inflammation, accumulation of immune cells and proteases/anti-proteases imbalance associated with chronic obstructive pulmonary disease and emphysema. Objectives: We studied Cd toxicity on U-937 monocytoid cells and its influence on matrix metalloproteinase-9 (MMP-9) and its tissue inhibitor (TIMP1) levels. Methods: U-937 cells were cultured and treated with either concentrations of 1.0, 10.0 or 50.0 ?M cadmium chloride. Cytotoxicity percentages were measured by activity assay of lactate dehydrogenase released into culture medium of treated and the control cells. MMP-9 and TIMP-1 levels were determined by ELISA. Zymography technique was used to quantify MMP-9 gelatinolytic activity in culture media of U-937 cells. Alterations in MMP-9 and TIMP-1 gene expressions in response to Cd were analyzed by real-time PCR method. Results: Cd found to be dose-dependently cytotoxic where 50.0 ?M Cd significantly increased LDH leakage from the cells (p Conclusion: These results suggest that Cd has direct detrimental effects on cell viability, MMPs activity and protease/anti-protease balance which may contribute to alveolar wall destruction and pulmonary diseases. Keywords: Cadmium, MMP-9, monocytic cells, TIMP-1

Acute Cadmium Exposure Causes Systemic and Thromboembolic Events in Mice

Cadmium (Cd), an environmental and industrial pollutant, poses a potential threat and affects many systems in human and animals. Although several reports on Cd toxicity were presented, the acute effect of Cd on systemic and thrombotic events was not reported so far. Cd (2.284 mg/kg) or saline (control) was injected intraperitoneally (ip), and the systemic parameters were assessed in mice. Compared to control group, acute intraperitoneal injection of Cd, in mice showed significant quickening of platelet aggregation (P<0.001) leading to pial cerebral thrombosis. Likewise, Cd exposure caused a significant increase in white blood cell numbers (P<0.05) indicating the occurrence of systemic inflammation. Also, alanine aminotransferase (ALT) (P<0.05) and creatinine (P<0.01) levels were both significantly increased. Interestingly, the superoxide dismutase activity was significantly decreased in Cd treated group compared to control group (P<0.001), suggesting the occurrence of oxidative stress. We conclude that the Cd exposure in mice causes acute thromboembolic events, oxidative stress and alter liver and kidney functions.

Effect of cadmium on glutathione S-transferase and metallothionein gene expression in coho salmon liver, gill and olfactory tissues

The glutathione S-transferases (GSTs) are a multifunctional family of phase II enzymes that detoxify a variety of environmental chemicals, reactive intermediates, and secondary products of oxidative damage. GST mRNA expression and catalytic activity have been used as biomarkers of exposure to environmental chemicals. However, factors such as species differences in induction, partial analyses of multiple GST isoforms, and lack of understanding of fish GST gene regulation, have confounded the use of GSTs as markers of pollutant exposure. In the present study, we examined the effect of exposure to cadmium (Cd), a prototypical environmental contaminant and inducer of mammalian GST, on GST mRNA expression in coho salmon (Oncorhynchus kisutch) liver, gill, and olfactory tissues. GST expression data were compared to those for metallothionein (MT), a prototypical biomarker of metal exposure. Data mining of genomic databases led to the development of quantitative real-time PCR (qPCR) assays for salmon GST isoforms encompassing 9 subfamilies, including alpha, mu, pi, theta, omega, kappa, rho, zeta and microsomal GST. In vivo acute (8–48h) exposures to low (3.7ppb) and high (347ppb) levels of Cd relevant to environmental scenarios elicited a variety of transient, albeit minor changes (<2.5-fold) in tissue GST profiles, including some reductions in GST mRNA expression. In general, olfactory GSTs were the earliest to respond to cadmium, whereas, more pronounced effects in olfactory and gill GST expression were observed at 48h relative to earlier time points. Although evaluation of GSTs reflected a cadmium-associated oxidative stress response, there was no clear GST isoform in any tissue that could serve as a reliable biomarker of acute cadmium exposure. By contrast, metallothionein (MT) mRNA was consistently and markedly induced in all three tissues by cadmium, and among the tissues examined, olfactory MT was the most sensitive marker of cadmium exposures. In summary, coho salmon exhibit a complex GST tissue profile consisting of at least 9 isoforms, all of which are present in the peripheral olfactory system. Short-term exposure to environmental levels of Cd causes transient changes in salmon GST consistent with oxidative stress, and in some cases, includes a loss of GST. In a biomarker context, however, monitoring of tissue MT mRNA expression, especially in the peripheral olfactory system, may be of greater utility for assessing short-term environmental exposures to cadmium.

Histopathological and biochemical alternations of the heart induced by acute cadmium exposure in the freshwater crab Sinopotamon yangtsekiense

Cadmium (Cd) is a highly toxic element in water. Its toxicity has been attributed to oxidative stress mediated by free radicals. Here we investigated the effects of Cd on the histopathology, antioxidant enzymes and lipid peroxidation of crustacean heart. The freshwater crabs Sinopotamon yangtsekiense were exposed to different concentrations of Cd for 1, 3, 5 and 7 d. After exposure, histological abnormalities were discovered, including myocardial edema, vacuolar and vitreous degeneration, and infiltration of inflammatory cells. Additionally, alterations in nuclei, mitochondria, rough endoplasmic reticulum as well as myofibrils were observed. Meanwhile, superoxide dismutase (SOD) activity was significantly increased after Cd exposure. Catalase (CAT) activity was only increased in the group exposed to 14.50 mg L −1 Cd on day 5 and decreased with increasing Cd concentration and exposure time. Glutathione peroxidase (GPx) activity was increased in groups treated with 29.00, 58.00 and 116.00 mg L −1 on days 1 and 3, and decreased thereafter. Besides, malondialdehyde (MDA) levels were significantly increased after 3 d of Cd exposure at all the indicated concentrations. These results showed that acute Cd exposure led to harmful effects on the histology of crab heart, which are most likely linked to Cd-induced oxidative stress.

Another Mechanism behind Cadmium Toxicity: Impaired NAT-Dependent Pathway Alters Chemical Biotransformation

Cadmium is a complex carcinogen that may contribute to carcinogenesis through multiple mechanisms, including inhibition of enzymes that help repair damaged DNA. A new study provides information on another possible mechanistic pathway by revealing that cadmium impairs NAT-dependent carcinogen metabolism as demonstrated by altered biotransformation of environmental aromatic amines (AAs) [EHP 118(12):1685–1691; Ragunathan et al.]. Cadmium accumulates in body tissues and causes disease of the lungs, kidneys, liver, testes, prostate, and bladder. It also is thought to potentiate the carcinogenicity of many common workplace chemicals. NATs, or arylamine N-acetyltransferases, are metabolic enzymes known to play a major role in the biotransformation of exogenous chemicals including AAs, many of which are known or suspected human carcinogens. In the current study the authors exposed purified NAT enzymes to cadmium and found the exposure led to rapid and irreversible functional impairment—removing the cadmium could not restore enzyme activities. They also exposed lung epithelial cells and laboratory mice to cadmium, then assessed NAT acetylation activity in the cells and mouse tissue samples. Biologically relevant concentrations of cadmium similar to those found in the lung tissue of heavy smokers impaired the NAT-dependent acetylation of carcinogenic AAs in lung epithelial cells, and NAT activity was strongly impaired in multiple tissues of mice exposed to cadmium. These findings indicate acute cadmium exposure can alter the metabolism of carcinogenic AAs through impairment of the NAT-dependent pathway, with potentially important toxicologic effects—especially considering AAs are commonly found in cigarette smoke along with cadmium. The authors recommend further studies to address whether chronic cadmium exposure leads to similar effects.

Effects of Acute Cadmium Exposure on the Pituitary Gland of Podarcis sicula~!2009-11-18~!2010-03-08~!2010-05-14~!

Effects of Acute Cadmium Exposure on the Pituitary Gland of Podarcis sicula~!2009-11-18~!2010-03-08~!2010-05-14~!

Linking Molecular and Population Stress Responses in Daphnia magna exposed to cadmium

DNA microarrays can be used to measure environmental stress responses. If they are to be predictive of environmental impact, we need to determine if altered gene expression translates into negative impacts on individuals and populations. A large cDNA microarray (14000 spots) was created to measure molecular stress responses to cadmium in Daphnia magna,the mostwidely used aquatic indicator species, and relate responses to population growth rate (pgr). We used the array to detect differences in the transcription of genes in juvenile D. magna (24 h old) after 24 h exposure to a control and three cadmium concentrations (6, 20, and 37 microg Cd2+ L(-1)). Stress responses at the population level were estimated following a further 8 days exposure. Pgr was approximately linear negative with increasing cadmium concentration over this range. The microarray profile of gene expression in response to acute cadmium exposure begins to provide an overview of the molecular responses of D. magna, especially in relation to growth and development. Of the responding genes, 29% were involved with metabolism including carbohydrate, fat and peptide metabolism, and energy production, 31% were involved with transcription/translation, while 40% of responding genes were associated with cellular processes like growth and moulting, ion transport, and general stress responses (which included oxidative stress). Our production and application of a large Daphnia magna microarray has shown that measured gene responses can be logically linked to the impact of a toxicant such as cadmium on somatic growth and development, and consequently pgr.