Acute Cadmium Exposure Research Articles

The effect of different types of microplastic and acute cadmium exposure on the Mytilus galloprovincialis (Lamarck, 1819)

Microplastic (MP) pollution is a pressing issue for both environmental health and the safety of human food sources. This study provides a comprehensive analysis of the effects of MPs on Mediterranean mussels (Mytilus galloprovincialis, Lamarck 1819), focusing on the food safety risks associated with MP and cadmium (Cd) exposure in these organisms intended for consumption. The retention of different polymer types of MPs in mussels was specifically evaluated, and the influence of Cd on MP retention across these polymers was investigated. Mussels were exposed to polystyrene (PS), polypropylene (PP), and polyethylene terephthalate (PET) MPs individually and in combination with the toxic metal Cd for a duration of 7 days. Antioxidant enzymes, oxidative stress parameters, and digestive system enzyme activities, selected as biomarkers for Cd and MPs pollution, were assessed. Furthermore, human consumption risk evaluations and limits regarding mussel intake were analysed in terms of food safety. The results suggest that exposure to Cd, MPs, or their combination induces oxidative stress, tissue damage, and neurotoxicity. Alterations in digestive enzyme activities could impact the mussels' energy acquisition from food and their capacity to conserve energy reserves. The estimated daily intake (EDI), provisional tolerable weekly intake (PTWI), target hazard quotient (THQ), and target cancer risk (TCR) levels for all groups surpassed established limits, implying a significant health risk for humans consuming these products. These results underscore the potential health risks for humans associated with consuming mussels exposed to Cd and/or MPs and provide valuable data for monitoring pollution levels and ecological risks in aquatic organisms. Additionally, our findings reveal that the retention of Cd in mussel tissues varies significantly after exposure, with combinations of PET and Cd showing lower levels of Cd accumulation compared to other groups, suggesting a differential interaction that influences Cd retention.

The Protective Effects of Ganoderma lucidum Active Peptide GLP4 on Lung Injury Induced by Cadmium Poisoning in Mice.

Ganoderma triterpenes and spore powder have shown promising results in mitigating cadmium-induced renal and hepatic injuries. Ganoderma lucidum active peptide GLP4 is a natural protein with dual antioxidant activities derived from the mycelium of Ganoderma lucidum. However, its efficacy in alleviating cadmium-induced lung injury remains unexplored. This study aims to investigate the protective effects of GLP4 against cadmium-induced lung injury in mice. Mice were exposed to cadmium chloride via nebulization to induce lung injury. The protective effect of GLP4 was assessed by measuring the total cell count in BALF, levels of inflammatory cytokines, and the expression of NLRP3 in lung tissues a through histopathological examination of lung tissue changes. The results showed that GLP4 significantly mitigated histopathological damage in lung tissues, decreased the secretion of inflammatory cytokines, and reduced the expression of NLRP3, which was elevated in cadmium-exposed mice. In vitro studies further revealed that GLP4 inhibited the cadmium-induced activation of the NLRP3 inflammasome. Notably, acute cadmium exposure by the respiratory tract did not affect the liver and kidneys of the mice. The findings suggest that GLP4 reduces cadmium-induced lung injury in mice by inhibiting the activation of the NLRP3 inflammasome, which provides a theoretical foundation for using Ganoderma lucidum as a preventive and therapeutic agent against cadmium poisoning.

Selenium-enriched crude polysaccharide from Rosa roxburghii Tratt ameliorates cadmium-induced acute kidney injury in mice by modulating intestinal microorganisms

Cadmium is a toxic heavy metal that can cause serious damage to the body. It can trigger the oxidative stress response and damage various organs of the body (kidney, liver, brain, lung, testis, etc.). Selenium polysaccharides are considered to possess better antioxidant, immune regulation, and heavy metal removal activities than other polysaccharides, But few reports focused on Selenium Polysaccharides in Rosa roxburghii Tratt. The purpose of this study was to isolate crude polysaccharides (RRP), and crude Selenium polysaccharides (SeRRP) from Rosa roxburghii Tratt fruit and determine their structure, antioxidant activity, and protective effects on cadmium-exposed mice (PONY-2020-FL-62). Results showed that SeRRP had lower half-maximal inhibitory concentration (IC50) and higher superoxide dismutase (SOD) activity. The intake of food and body weight decreased, while the kidney index and liver index increased significantly after acute cadmium exposure. Most significantly, SeRRP ameliorates kidney injury by improving the kidney index. Furthermore, changes in the gut microbiota may be related to SeRRP or RRP. SeRRP and RRP decreased the Firmicutes/Bacteroidetes ratio, and increased the abundance of beneficial bacteria (Lachnospiraceae, Muribaculaceae, and Ruminococcaceae, etc.). These findings indicate that SeRRP and RRP have the potential to be functional food against oxidant and heavy metal exposure.

Quaercetin Improves Renal Functional Disorder and Dyslipidemia Caused by Acute Cadmium Exposure

Heavy metal toxicity and bioaccumulation caused severe damage to soil, water and environment as a result of industrialization/urbanization activities in developing and developed countries. This damage has affected different trophic levels including plants, animals and humans and has become a global concern. The use of various phytonutrients such as Quercetin (QE) has increased in recent years to avoid toxicity caused by heavy metals. Among different heavy metals, cadmium (Cd) toxicity is a major issue in the countries. Cd is a toxic heavy metal that can damage the kidneys and cause dysregulation in many lipid metabolic pathways. However, the number of studies on renal dysfunction and dyslipidemia caused by Cd is limited. We found that Cd causes renal dysfunction and dyslipidemia, and QE ameliorates these Cd-induced damages. Our results showed that Cd increased urea, uric acid, creatnine, alkene phosphatase (ALP), total bilirubin (TBIL) levels compared to the control group, while QE improved other parameters except TBIL. In addition, our findings showed that Cd increased total glyceride (TG), total cholesterol (TC), low-density lipoprotein (LDL) and lactate dehydrogenase (LDH) levels and decreased high-density lipoprotein (HDL) levels. It was noted that QE tended to improve this dyslipidemia picture. The data presented here demonstrated that QE has a clear protective role against dyslipidemia and renal function against Cd toxicity through its hypolipidemic and antioxidative action.

The Protection of Zinc against Acute Cadmium Exposure: A Morphological and Molecular Study on a BBB In Vitro Model.

Cadmium (Cd) is a well-known occupational and environmental pollutant worldwide, and its toxicity is widely recognised. Cd is reported to increase the permeability of the blood–brain barrier (BBB) and to penetrate and accumulate in the brain. Although many lines of evidence show that Cd toxicity is induced by different mechanisms, one of the best known is the Cd-dependent production of reactive oxygen species (ROS). Zinc is a trace element known as coenzyme and cofactor for many antioxidant proteins, such as metallothioneins and superoxide dismutase enzymes. To date, very little is known about the role of Zn in preventing Cd-induced blood–brain barrier (BBB) alterations. The goal of this study was to test the Zn antioxidant capacity against Cd-dependent alterations in a rat brain endothelial cell line (RBE4), as an in vitro model for BBB. In order to mimic acute Cd poisoning, RBE4 cells were treated with CdCl2 30 µM for 24 h. The protective role of ZnCl2 (50 µM) was revealed by evaluating the cell viability, reactive oxygen species (ROS) quantification, cytochrome C distribution, and the superoxide dismutase (SOD) protein activity. Additionally, the effectiveness of Zn in counteracting the Cd-induced damage was investigated by evaluating the expression levels of proteins already known to be involved in the Cd signalling pathway, such as GRP78 (an endoplasmic reticulum (ER) stress protein), caspase3 pro- and cleaved forms, and BAX. Finally, we evaluated if Zn was able to attenuate the alterations of zonula occludens-1 (ZO-1), one of the tight-junction (TJ) proteins involved in the formation of the BBB. Our data clearly demonstrate that Zn, by protecting from the SOD activity impairment induced by Cd, is able to prevent the triggering of the Cd-dependent signalling pathway that leads to ZO-1 dislocation and downregulation, and BBB damage.

Activation of multiple proteolysis systems contributes to acute cadmium cytotoxicity.

Cadmium exhibits both toxic and carcinogenic effects, and its cytotoxicity is linked to various cellular pathways, such as oxidative stress, ubiquitin-proteasome, and p53-mediated response pathways. The molecular mechanism(s) underlying cadmium cytotoxicity appears to be complex, but remains largely unclear. Here, we examined the effects of cadmium on the protein catabolism using two surrogate markers, DNA topoisomerases I and II alpha and its contribution to cytotoxicity. We have found that cadmium exposure induced time- and concentration-dependent decreases in the protein level of surrogate markers and therefore suggest that cadmium may be involved in proteolysis system activation. A pharmacological study further revealed the novel role(s) of these proteolytic activities and reactive oxygen species (ROS) in the cadmium-induced acute toxicity: (i) Proteasome inhibition only partially relieved the cadmium-induced proteolysis of topoisomerases; (ii) Moreover, we report for the first time that the activation of metalloproteases, serine proteases, and cysteine proteases contributes to the acute cadmium cytotoxicity; (iii) Consistent with the notion that both ROS generation and proteolysis system activation contribute to the cadmium-induced proteolysis and cytotoxicity, the scavenger N-acetylcysteine and aforementioned protease inhibition not only reduced the cadmium-induced topoisomerase degradation but also alleviated the cadmium-induced cell killing. Taken together, acute cadmium exposure may activate multiple proteolytic systems and ROS formation, subsequently leading to intracellular damage and cytotoxicity. Thus, our results provide a novel insight into potential action mechanism(s) by which cadmium exerts its cytotoxic effect and suggest potential strategies to prevent cadmium-associated acute toxicity.

Endoplasmic reticulum stress-mediated autophagy activation is involved in cadmium-induced ferroptosis of renal tubular epithelial cells

Acute cadmium (Cd) exposure is a significant risk factor for renal injury and lacks effective treatment strategies. Ferroptosis is a recently identified iron-dependent form of nonapoptotic cell death mediated by membrane damage resulting from lipid peroxidation, and it is implicated in many diseases. However, whether ferroptosis is involved in Cd-induced renal injury and, if so, how it operates. Here, we show that Cd can induce ferroptosis in kidney and renal tubular epithelial cells, as demonstrated by elevation of intracellular iron levels and lipid peroxidation, as well as impaired antioxidant production. Treatment with a ferroptosis inhibitor alleviated Cd-induced cell death. Intriguingly, we established that Cd-induced ferroptosis depended on endoplasmic reticulum (ER) stress, by demonstrating that Cd activated the PERK-eIF2α-ATF4-CHOP pathway and that inhibition of ER stress reduced ferroptosis caused by Cd. We further found that autophagy was required for Cd-induced ferroptosis because the inhibition of autophagy by chloroquine mitigated Cd-induced ferroptosis. Furthermore, we showed that iron dysregulation by ferritinophagy contributed to Cd-induced ferroptosis, by showing that the iron chelator desferrioxamine alleviated Cd-induced cell death and lipid peroxidation. In addition, ER stress is likely activated by MitoROS which trigger autophagy and ferroptosis. Collectively, our results indicate that ferroptosis is involved in Cd-induced renal toxicity and regulated by the MitoROS-ER stress-ferritinophagy axis.

Acute cadmium exposure induces GSDME-mediated pyroptosis in triple-negative breast cancer cells through ROS generation and NLRP3 inflammasome pathway activation

Cadmium (Cd) exposure can exert an impact on carcinogenicity of breast cancer, however, the mechanism is not fully understood in triple-negative breast cancer (TNBC). We performed a TNBC MDA-MB-231 cell model and assessed the toxic effect of Cd exposure (0, 10, 20, 50, 60, 80 μM). Cd reduced cell viability in a time- and dose-dependent manner, followed by cell cycle arrest in S phase with alterations of cyclin 1A1, cyclin 1D1 and CDK2. Lactate dehydrogenase (LDH) release, apoptosis and pyroptosis were increased, which were relieved by z-VAD. Elevated ROS and NLRP3, caspase-1, IL-1β and IL-18 were detected, which was attenuated by N-acetylcysteine. Increased bax and decreased caspase-8, caspase-9 and caspase-3 were found. gasdermin E (GSDME) was activated with cleavage of GSDME-NT, which was retarded by z-VAD. Additionally, p38 MAPK signaling pathway was activated. Our data demonstrate GSDME-activated pyroptosis in Cd toxicity, implying a potential impact on TNBC.

Microarray analysis of the mechanism of liver injury induced by acute cadmium exposure in rats

Microarray analysis of the mechanism of liver injury induced by acute cadmium exposure in rats

Long-term effects of acute cadmium exposure on testis immune privilege

Cadmium (Cd) is a widespread and non-biodegradable pollutant of great concern to human health. This element can affect cellular signal transduction and cell-to-cell interaction in the testis. Immune tolerance towards auto- and alloantigens is an important component of testis immunity. It is involved in spermatogenesis and hormone secretion. Plus, the immune tolerance may help to reveal the changes in testis immunity over a long period after Cd exposure. The current research was aimed at investigating the long-term effects of acute Cd exposure on testis immunity by means of elicitation of testicular immune cell composition shift induced by Cd. Cadmium chloride was intraperitoneally injected at 3 mg Cd/kg to mice. After that testis interstitial cells were stained with surface markers for leukocyte and lymphocyte subpopulations (CD45, CD11b, CD3, CD4, CD8, CD25) and analyzed cytofluorimetrically by week 4, 6, 8 and 12 after Cd administration (Cd group). To identify the delayed effects of cadmium on immune tolerance two groups of animals were subjected to intratesticular allotransplantation of neonatal testis (groups ITT and Cd+ ITT). One of the groups was administered with Cd four weeks before the transplantation (Cd+ITT group). I group served as a control that did not undergo any transplantation or Cd injection. For a better demonstration of the phenomenon of immunological tolerance of the testicles, an additional group (UKT group) was used which got grafts under the kidney capsule (non-immune privileged site).Investigation of the cell population showed that CD45+, CD11b+, CD4+, CD8+ cells were permanently present in testicular interstitial tissue in I group. Intratesticular testis transplantation increased the proportion of CD11b+ but did not have such a pronounced effect on CD8+ cells in ITT group. Moreover, the transplantation elevated CD4+ CD25+ cells known for their immunosuppressive property and promoted graft development by week 2 (histological data). Cd injection resulted in severe inflammation that quenched by week 4 (Cd and Cd+ ITT groups). This time point was chosen for transplantation in Cd+ ITT group. Such Cd pretreatment led to a high CD8+ cell proportion and to the delayed appearance of CD4+ CD25+ cells by week 2 (Cd+ ITTgroup). The finding is consistent with the impairment of graft development in Cd+ ITTgroup pretreated with Cd. Observation suggest that Cd pretreatment was associated with disproportion of interstitial immune cell populations which resulted in the impairment of immunoprotective function of the testis. The impairment of testis immunity showed itself only after several weeks of Cd administration, and only when the recipient testis immunity was provoked by alloantigens of donor testes.

Morphology, Histopathology and Hematology as Biomarkers of Cadmium Toxicity in Field Rats

Background: Cadmium is known as a unique heavy metal compared to others, due to its long half-life, low discharge from the body, toxicity at low concentrations and accumulation in tissues. Methods: The effects of chronic and acute Cadmium (Cd) exposure were investigated on the morphology and histopathology of 24 field rats (Millardia meltada). The rats were divided into two groups of 12 each, then sub-divided into: one control and two treatment sub-groups with Cd in the feed or water. The treatment subgroups received either 15mg/kg (low) or 30mg/kg (high) Cd concentration in the feed. Results: Hemorrhagic spots and fibrosis were observed in the liver of Cd treated rats compared to the controls. Also, necrosis, dilation, and calcinosis occurred in the renal tubules of the treatment groups compared to the controls. The levels of hemoglobin, red and white blood cells, hematocrit, and mean corpuscular hemoglobin were reduced, while mean corpuscular volume and hemoglobin concentrations were increased. Conclusion: This study reports the morphological, pathological and hematological abnormalities in the blood, liver and kidneys of rats due to Cd toxicity, which may be considered as the biomarkers of cadmium toxicity in other experimental mammals.

Cadmium Induces Acute Liver Injury by Inhibiting Nrf2 and the Role of NF-κB, NLRP3, and MAPKs Signaling Pathway.

Acute Cadmium (Cd) exposure usually induces hepatotoxicity. It is well known that oxidative stress and inflammation causes Cd-induced liver injury. However, the effect of nuclear factor erythroid 2-related factor 2 (Nrf2) in Cd-induced liver injury is not completely understood. In this study, we observed Cd-induced liver damage and the potential contribution of Nrf2, nuclear factor-κB (NF-κB), Nod-like receptor 3 (NLRP3), and mitogen-activated protein kinases (MAPKs) signaling pathways. Changes in serum transaminases and proinflammatory cytokines expression showed that Cd could induce acute hepatotoxicity. Moreover, Nrf2 and its downstream heme oxygenase 1 (HO-1) were inhibited by Cd exposure, and Kelch-like ECH-associated protein 1 (Keap1), the inhibitory protein of Nrf2, was increased. Furthermore, NF-κB, NLRP3, and MAPKs signaling pathways were all activated by Cd intoxication. In conclusion, the inhibition of Nrf2, HO-1, and the activation of NF-κB, NLRP3, and MAPKs all contribute to Cd-induced liver injury.

The Effect of Acute Cadmium Exposure on the Vascular Endothelial Barrier Antigen and Astrocyte Morphology in the Developing Rat Central Nervous System

Cadmium is a non‐biodegradable heavy metal and a major worldwide environmental pollutant. Clinical and experimental studies have documented the neurotoxic and behavioral effects of cadmium. However, the exact pathophysiologic mechanism(s) of the toxicity of cadmium for the human central nervous system is not completely understood. A literature review indicates that disruption of the blood‐brain barrier (BBB) structures is a key event in the pathogenesis of central nervous system disorders including cadmium neurotoxicity and infectious diseases. Several BBB‐associated proteins, including occludins, junctional adhesion molecules and claudins, among others, have been identified and used for evaluating BBB disruption under pathological conditions. A developmentally regulated rat blood‐brain barrier (BBB)‐specific capillary endothelial marker, the endothelial barrier antigen (EBA), has been previously isolated and classified by Sternberger and others. In previous studies, we have demonstrated that anti‐EBA exclusively recognizes barrier‐competent microvessels in the rat central and peripheral nervous system (CNS and PNS) and is negative in endothelial cells of peripheral tissues such as the heart and kidney. The antigen is also absent in brain microvessels possessing fenestrated endothelia such as the median eminence, organum vasculosum of lamina terminalis (ovalt) and pineal gland. In our current study, we applied a double, sequential indirect immunofluorescent protocol with anti‐EBA and an antibody directed against glial fibrillary acidic protein (GFAP), to examine the immunoreactivity patterns and morphological alterations in BBB microvessels and astrocytes, following acute exposure to a single, high dose of cadmium in young rats. We detected a moderate reduction in immunoreactivity and number of microvessels labelled by the anti‐EBA in the forebrain, cerebellum and midbrain in cadmium‐exposed rats compared to normal controls. Within the white and gray matter of cadmium‐exposed brains, we observed weakly GFAP‐reactive astrocytes displaying cell bodies with ill‐defined borders and blurry cytoplasm. The astrocyte nuclei appeared markedly enlarged, intensely hyperchromatic and exhibited marked chromatin condensation with varying degree of nuclear fragmentation. The weakly GFAP‐positive cell processes were hypertrophic and showed less branching compared to the strongly GFAP‐positive, highly branched astrocytes. Thus, indicating that EBA is involved in the pathogenesis of cadmium neurotoxicity in the rat model system.Support or Funding InformationThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Molecular characterization of acutely and gradually heavy metal acclimated aquatic bacteria by FTIR spectraoscopy.

In the environment, bacteria can be exposed to the concentration gradient of toxic heavy metals (gradual) or sudden high concentration of them (acute). In both situations, bacteria get acclimated to toxic heavy metal concentrations. Acclimation causes metabolic and molecular changes in bacteria. In this study, we aimed to understand whether there are differences between molecular profiles of the bacteria (Brevundimonas, Gordonia and Microbacterium) which are under acute or gradual exposure to cadmium or lead by using ATR-FTIR spectroscopy. Our results revealed the differences between the acclimation groups in membrane dynamics including changes in the structure and composition of the membrane lipids and proteins. Furthermore, protein concentrations decreased in acclimated bacterial groups. Also, a remarkable increase in exopolymer production occurred in acclimated groups. Interestingly, bacteria under acute cadmium exposure produced the significantly higher amount of exopolymer than they did under gradual exposure. On the contrary, under lead exposure gradually acclimate strains produced significantly higher amounts of exopolymer than those of acutely acclimated ones. This information can be used in bioremediation studies to obtain bacterial strains producing a higher amount of exopolymer.

Toxic Effect of Acute Cadmium and Lead Exposure in Rat Blood, Liver, and Kidney.

Background: Cadmium and lead are widespread and non-biodegradable pollutants of great concern to human health. In real life scenarios, we are exposed to mixtures of chemicals rather than single chemicals, and it is therefore of paramount importance to assess their toxicity. In this study, we investigated the toxicity of Cd and Pb alone and as a mixture in an animal model of acute exposure. Methods: Experimental groups received a single treatment of aqueous solution of Cd-chloride (15 and 30 mg/kg body weight (b.w.) and Pb-acetate (150 mg/kg b.w.), while the mixture group received 15 mg Cd/kg b.w. and 150 mg Pb/kg b.w. Toxic effects of individual metals and their mixture were investigated on hematological and biochemical parameters, and the redox status in the plasma, liver, and kidneys of treated Wistar rats. Results: Tissue-specific changes were recorded in various parameters of oxidative damage, while the accumulation of metals in tissues accompanied the disturbances of both hematological and biochemical parameters. It was observed that the level of toxic metals in tissues had a different distribution pattern after mixture and single exposure. Conclusions: Comprehensive observations suggest that exposure to Cd and Pb mixtures produces more pronounced effects compared to the response observed after exposure to single metal solutions. However, further research is needed to confirm toxicokinetic or toxicodynamic interactions between these two toxic metals in the organisms.

Toxic Effects of Acute Cadmium and Lead Exposure in Rat Blood, Liver, and Kidney

Toxic Effects of Acute Cadmium and Lead Exposure in Rat Blood, Liver, and Kidney

Protective effect of tetrahydrobiopterin on hepatic and renal damage after acute cadmium exposure in male rats

ABSTRACTCadmium (Cd) has been recognized as one of the most important environmental and industrial pollutants. This study investigated the impact of acute exposure to Cd on oxidative stress and the inflammatory marker interleukin-6 (IL-6) in the plasma of rats and the histological picture of liver and kidney, as well as to examine the potential protective effect of tetrahydrobiopterin (BH4). Methods: Rats were divided into control group, Cd group that received a single intraperitoneal (i.p.) dose of 4 mg/kg b.w. of CdCl2 and BH4+ Cd group that received a single dose of BH4 (20 mg/kg, i.p.) and subsequently exposed to a single dose of Cd 24 h after the BH4 treatment. Results: Cd increased the plasma levels of hepatic enzymes (ALT and AST), urea, creatinine, malondialdehyde (MDA), and IL-6 and decreased the superoxide dismutase (SOD) activity. Also, it induced histopathological alterations in the liver with severe degeneration, especially in centrilobular zones. Renal tubular epithelium showed vacuolated cytoplasm and dense nuclei. VEGF expression was mild. Ultrastuctural changes were seen in some renal tubules. The nuclei appeared distorted with electron dense chromatin. Mitochondria with destructed cristae were observed. BH4 pretreatment had protective effects, since it significantly reduced the levels of IL-6 and ameliorated the alteration in oxidative status biomarkers induced by Cd. Improvement of histopathological alterations was observed in Cd-groups. The nuclei were vesicular euchromatic, intact mitochondria and normal appearance of the filtration membrane. Moderate expression of VEGF was noted. Conclusion: This study has provided clear evidence for the protective efficacy of BH4 against experimental Cd toxicity.

Chronic cadmium exposure induced hepatic cellular stress and inflammation in aged female mice.

Previous studies have revealed that acute cadmium (Cd) exposure led to inflammation in different organs through an oxidative stress mechanism. However, whether chronic Cd exposure induces inflammation in liver and the mechanistic link between inflammation and cell stress remains unclear. In the present study, we investigated the effects of chronic Cd exposure on hepatic cellular stress and inflammatory responses. Female CD1 mice were administrated with CdCl2 (10 and 100mg/L) in drinking water for 57weeks. Our results showed that the mRNA levels of Inos and the protein content of HO-1, markers of oxidative stress, were markedly increased in Cd-treated mice. In addition, the protein level of GRP78, the chaperone of endoplasmic reticulum (ER) stress, was significantly increased in Cd-treated mice. The expression of the proteins CHOP and peIF2α, two proteins downstream of ER stress, was also upregulated in the Cd-100mg/L and Cd-10mg/L group, respectively. Moreover, there were increased inflammatory cells existing in liver after Cd administration. Besides, there was a significant elevation in the mRNA level of Mip-2, Il-10 and Il-12 in the Cd-100mg/L group. The mRNA level of Tgf-β was also upregulated in Cd-treated mice. Moreover, we also found that the number of Ki67-positive hepatic cells was increased in the Cd-10mg/L group. Hence, our results indicated that chronic Cd exposure induced oxidative stress, ER stress, inflammatory responses and proliferation in the liver of aged female mice.

Urinary cadmium concentrations and metabolic syndrome in U.S. adults: The National Health and Nutrition Examination Survey 2001–2014

BackgroundLow to moderate acute cadmium exposure has been associated with increased risk of chronic diseases, such as cardiovascular and kidney disease. Little is known about the association between urinary cadmium levels—an indicator of longer-term exposure—and metabolic syndrome (MetS). MethodsWe analysed data from 3982 participants aged 20–<80 years of the National Health and Nutrition Examination Survey 2001–2014. Urinary cadmium levels were measured and adjusted for creatinine using spot urine samples. Cadmium levels were evaluated in quintiles (Q). MetS was defined by National Cholesterol Education Program's Adult Treatment Panel III report criteria. Prevalence odds ratios (OR) and 95% confidence intervals (CI) were calculated using multivariable logistic regression accounting for complex survey design, while adjusting for potential confounders and stratifying by sex and smoking status. ResultsIn the overall study population, there was a marginal inverse association between urinary cadmium and MetS (adj. OR for Q5 versus Q1: 0.7; 95% CI: 0.5–1.0). Sex stratified models were similar. When examining individual components of MetS, participants with higher levels of urinary cadmium had decreased odds of abdominal obesity (adj. OR for Q5 versus Q1 0.4; 95% CI: 0.3–0.6), but increased odds for low HDL (adj. OR for Q5 versus Q1 2.1; 95% CI: 1.4–3.1). Among current smokers, higher urinary cadmium was associated with increased odds of MetS, hypertension, and low HDL even after accounting for serum cotinine—a marker of smoking intensity. ConclusionsHigher levels of urinary cadmium, a marker of long term exposure, were not associated with an increased risk of MetS in the overall study population. However, higher urine cadmium was associated with altered MetS components. Current smokers were the most vulnerable group, with higher long-term cadmium exposure being associated with increased risk of MetS, low HDL, and hypertension.

Exposure to Cadmium Impairs Sperm Functions by Reducing CatSper in Mice

Background: Cadmium (Cd), a common environmental heavy metal and endocrine disruptor, is known to exert toxic effects on the testes. However, the mechanisms accounting for its toxicity in mature spermatozoa remain unclear. Methods: Adult male C57BL/6 mice were orally administered with CdCl₂ for 5 weeks at 3 mg·kg^-1·day^-1. Additionally, mouse spermatozoa were incubated in vitro with different doses of CdCl₂ (0, 10, 50, 250 µM). Several sperm functions including the sperm motility, viability and acrosome reaction (AR) ratio were then examined. Furthermore, the current and expression levels of both the sperm-specific Ca²⁺ channel (CatSper) and the sperm-specific K⁺ channel (KSper) were evaluated by patch-clamping and western blotting, respectively. Results: Our data showed that the motility, viability and AR of sperm exposed to cadmium significantly decreased in vivo and in vitro. Interestingly, these changes were correlated with changes in CatSper but not KSper. Conclusion: The findings indicate sperm dysfunction during both chronic and acute cadmium exposure as well as a specific role for CatSper in the reproductive toxicity of cadmium.