Cadmium Exposure Research Articles

Prenatal and childhood exposure to endocrine-disrupting chemicals and early thelarche in 8-year-old girls: A prospective study using Bayesian kernel regression

BackgroundStudies on the combined effects of persistent and non-persistent endocrine-disrupting chemicals (EDCs) on puberty are insufficient. To date, no studies have analyzed breast development at age 8 years, a key criterion for determining precocious puberty. We investigated the relationship between prenatal or childhood exposure to EDC mixtures and early thelarche, defined as breast development before age 8 years in girls. MethodsThis prospective study included 211 girls with data on prenatal and 8-year-old exposure of cadmium (Cd), lead, mercury, bisphenol-A (BPA), 3-phenoxybenzoic acid, and three phthalate metabolites from the Environment and Development of Children cohort. Prenatal exposure was assessed through samples from pregnant women at 14–27th weeks of gestation. Tanner staging was assessed by a pediatric endocrinologist. The relationship between single and mixed chemical exposures and outcomes was assessed using logistic regression, generalized additive models (GAM), and Bayesian kernel machine regression (BKMR) models. ResultsEarly thelarche was observed in 42 (19.9%) girls at age 8 years. In the logistic regression models, the risk of early thelarche increased with increased exposure to Cd in their mothers (adjusted odds ratio [aOR] per interquartile range [IQR] = 1.80, 95% confidence interval [CI] 1.23–2.65) but decreased with prenatal BPA exposure (aOR per IQR = 0.57, 95% CI 0.35–0.92). None of the 8-year-old chemical exposures was associated with early thelarche. In the GAM, early thelarche was positively correlated with prenatal Cd and inversely associated with prenatal BPA exposure (p = 0.004 for Cd and p = 0.036 for BPA). In the BKMR models, an increase in log-transformed prenatal Cd concentrations from the 25th to 75th percentile was associated with an increase in the estimated probability of early thelarche at age 8 years (risk difference: 0.46 [95% credible interval: 0.04–0.88]) when other chemicals were set at their median values. ConclusionsConsidering the combined effects of persistent and non-persistent chemical mixtures, maternal Cd exposure during the second trimester may be associated with early thelarche in 8-year-old girls.

ABA-regulated MAPK signaling pathway promotes hormesis in sugar beet under cadmium exposure

Sugar beet (Beta vulgaris L.) shows potential as an energy crop for cadmium (Cd) phytoremediation. To elucidate its in vivo response strategy to Cd exposure, seedlings were treated with 1, 3, and 5 mmol/L CdCl2 (Cd-1, Cd-3, and Cd-5) for 6 h, using 0 mmol/L CdCl2 (Cd-0) as the control. The results showed that Cd-3 promoted a unique “hormesis” effect, leading to superior growth performance, increased levels of chlorophyll, soluble protein, and SOD activity, and reduced MDA content in sugar beet, compared to Cd-1, Cd-5, and even Cd-0. GO and KEGG enrichments and PPI networks of transcriptomic analysis revealed that the differentially expressed genes (DEGs) were primarily involved in lipid metabolism, cellular protein catabolism, and photosynthesis. Notably, the MAPK signaling pathway was significantly enriched only under Cd-3, with the up-regulation of ABA-related core gene BvPYL9 and an increase in ABA content after 6 h of Cd exposure. Furthermore, overexpression of BvPYL9 in Arabidopsis thaliana (OE-1 and OE-2) resulted in enhanced growth (fresh weight, dry weight, and root length), as well as higher ABA and soluble protein contents under different Cd treatments. Cd-induced transcriptional responses of BvPYL9 were also evident in OE-1 and OE-2, especially at 10 µmol/L, indicated by qRT-PCR. These findings suggest that ABA-mediated MAPK signaling pathway is activated in response to Cd toxicity, with BvPYL9 being a key factor in the cascade effects for the Cd-induced hormesis in sugar beet.

Toxic Effects of Cadmium Exposure on Hematological and Plasma Biochemical Parameters in Fish: A Review.

Cadmium (Cd) is a non-essential trace element that poses significant toxic effects on fish. This review focuses on hematological and plasma biochemical parameters as key indicators of fish health under Cd exposure. Hematological parameters, such as red blood cell (RBC) count, hemoglobin (Hb) concentration, and hematocrit (Ht), were selected for their critical role in oxygen transport and their sensitivity to Cd-induced disruptions, which often result in anemia and impaired oxygen delivery to tissues. Mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), and mean corpuscular hemoglobin concentration (MCHC) provide further insights into erythropoiesis and hemoglobin synthesis, both of which are essential for assessing Cd toxicity. Plasma biochemical parameters, including calcium, magnesium, glucose, cholesterol, total protein, and liver enzymes such as aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP), are crucial for understanding ionic balance, metabolic regulation, and organ function, especially in fish exposed to Cd. These biomarkers offer a comprehensive view of the physiological stress and organ damage caused by Cd toxicity. This review synthesizes literature findings on the toxic effects of Cd on these parameters. It also discusses potential mitigation strategies, including dietary supplementation with antioxidants and trace elements, to counteract the harmful effects of Cd exposure.

Determining the Feasibility of a Cadmium Exposure Model to Activate the Inflammatory Arm of PANoptosis in Murine Monocytes.

A prevalence of cigarette smoking can cause the accumulation of cadmium (Cd2+) in the lungs, kidneys, and blood. The effects of exposure can cause multiple chronic disease types to emerge in the affected organ systems. The only moderately effective therapeutic option is chelation therapy; the health risks associated with this therapy have caused much criticism. The disease types associated with Cd2+ toxicity have inflammatory components and greatly impact innate immunity. These factors are affected at the cellular level and cause pathways like apoptosis, pyroptosis, and necroptosis. A development in understanding these pathways stipulates that these three pathways act as one complex of pathways, known together as PANoptosis. The inflammatory mechanisms of PANoptosis are particularly interesting in Cd2+ toxicity due to its inflammatory effects. Proteins in the gasdermin family act to release inflammatory cytokines, like interleukin-1β, into the extracellular environment. Cytokines cause inflammatory disease pathologies like fibrosis and cancer. RAW 264.7 monocytes are key in the murine immune system and provide an excellent model to investigate Cd2+ toxicity. Exposure of 0-15 µM CdCl2 was sufficient to increase expression of cleaved gasdermin D (GSDMD) and gasdermin E (GSDME) in this cell type. Cd2+ also exhibits a dose-dependent cytotoxicity in this cell type.

Short-term respiratory cadmium exposure partially activates pulmonary NLRP3 inflammasome by inducing ferroptosis in mice

Cadmium (Cd) is a common environmental metal. Previous studies indicated that long-term respiratory Cd exposure caused lung injury and airway inflammation. The purpose of this study was to evaluate whether short-term respiratory Cd exposure induces pulmonary ferroptosis and NLRP3 inflammasome activation. Adult C57BL/6J mice were exposed to Cd by inhaling CdCl2 aerosol (0, 10, or 100 ppm) for 5 days. Serum and lung Fe2+ contents were elevated in Cd-exposed mice. Oxidized AA metabolites, the major oxidized lipids during ferroptosis, were upregulated in Cd-exposed mouse lungs. Pulmonary MDA content and 4-HNE-positive cells were increased in Cd-exposed mice. ACSL4 and COX-2, two lipoxygenases, were upregulated in Cd-exposed mouse lungs. Further analyses found that phosphorylated NF-kB p65 was elevated in Cd-exposed mouse lungs. Innate immune receptor protein NLRP3 and adapter protein ASC were upregulated in Cd-exposed mouse lungs. Caspase-1 was activated and IL-1β and IL-18 were upregulated in Cd-exposed mouse lungs. Fer-1, a specific inhibitor of ferroptosis, attenuated Cd-induced elevation of pulmonary NLRP3 and ASC, caspase-1 activation, and IL-1β and IL-18 upregulation. Finally, mitoquinone (MitoQ), a mitochondria-target antioxidant, suppressed Cd-caused ferroptosis and NLRP3 inflammasome activation. Our results demonstrate that ferroptosis might partially mediate Cd-evoked activation of NLRP3 inflammasome in the lungs.

Health Hazards Associated with Dietary Exposure of Female Rat to Cadmium-Contaminated Cooked Rice: Biochemical, Hormonal, and Histopathological Analysis.

The actual exposure, bioavailability, and body burden of dietary cadmium (Cd) vary with the food matrix. Here, we evaluated the health hazards of 45-day long-term exposure of growing Sprague-Dawley (SD) female rats to a natural and endogenous Cd-contaminated brown and white cooked rice dietary model. Cd was found mainly in the duodenum, kidney, and liver; the cecum and colon also contained substantial amounts of Cd in rats fed Cd-contaminated cooked white rice (cWR-test) but not Cd-contaminated cooked brown rice (cBR-test). Damage due to Cd exposure was reflected in liver dysfunction, altered estradiol levels, and distinctive pathologies in organ systems, although urinary Cd (U-Cd) excretion and blood Cd (B-Cd) were not detectable, suggesting that these are not the most accurate or appropriate biomarkers for evaluating dietary Cd exposure. Brown rice, despite being higher in Cd, can reduce Cd absorption and distribution in organs and increase the volume of Cd-containing feces, even achieving slightly higher excretion and lower apparent absorption rates of Cd than white rice, thereby reducing Cd damage to the body. The beneficial components of brown rice such as more dietary fiber, rice bran oil and polyphenol were speculated therefore to confer a degree of protection or repair. Nevertheless, the high apparent absorption levels observed here (> 5%) and signs of significant physical damage indicate that more stringent Cd intake guidelines and measures are needed to minimize Cd levels in rice.

Dietary Addition of Selenium Attenuates Cadmium-Induced Liver Injury in Grass Carp (Ctenopharyngodon idellus) by Reducing Oxidative Stress and Apoptosis

In order to investigate the effects of selenium (Se) against cadmium (Cd) toxicity, 180 healthy grass carp were separated into three groups and fed diets containing 0.147 (control group), 0.562, and 1.044 mg/kg of selenium Yeast throughout 60 days. In grass carp livers, malondialdehyde (MDA) content, antioxidant enzyme activities, and apoptosis-related gene expression were examined. As a result of acute exposure to cadmium, MDA content decreased significantly. With time, catalase (CAT), total superoxide dismutase (T-SOD), and glutathione peroxidase (GSH-Px) activities changed. The relative transcript levels of heavy metal scavenging genes abcc2 and mt2 were significantly reduced. The relative levels of expression of jnk, bax, caspase-3, caspase-8, and caspase-9 in apoptosis-associated factors were significantly elevated after cadmium exposure. Selenium-supplementation downregulated the expression of apoptosis-related factors. As compared to the control group, liver cells supplemented with selenium had a significantly lower apoptotic index. Comprehensive analysis showed that dietary selenium supplementation significantly attenuated cadmium-induced peroxidative damage and apoptosis in liver by increasing GSH-Px activity, and that cadmium toxicity could be alleviated by the addition of yeast selenium.

Hormetic responses to cadmium exposure in wheat seedlings: insights into morphological, physiological, and biochemical adaptations.

Cadmium is commonly recognized as toxic to plant growth, low-level Cd has promoting effects on growth performance, which is so-called hormesis. Although Cd toxicity in wheat has been widely investigated, knowledge of growth response to a broad range of Cd concentrations, especially extremely low concentrations, is still unknown. In this study, the morphological, physiological, and biochemical performance of wheat seedlings to a wide range of Cd concentrations (0-100 µΜ) were explored. Low Cd treatment (0.1-0.5µM) improved wheat biomass and root development by enhancing the photosynthetic system and antioxidant system ability. Photosynthetic rate (Pn) was improved by 5.72% under lower Cd treatment (1 µΜ), but inhibited by 6.05-49.85% from 5 to 100 µΜ. Excessive Cd accumulation induced oxidative injury manifesting higher MDA content, resulting in lower photosynthetic efficiency, stunted growth, and reduction of biomass. Further, the contents of ascorbate, glutathione, non-protein thiols, and phytochelatins were improved under 5-100 µΜ Cd treatment. The ascorbate peroxidase activity in the leaf showed a hormetic dose-response characteristic. Correlation analysis and partial least squares (PLS) results indicated that antioxidant enzymes and metabolites were closely correlated with Cd tolerance and accumulation. The results of the element network, correlation analysis, and PLS showed a crucial role for exogenous Cd levels in K, Fe, Cu, and Mn uptake and accumulation. These results provided a deeper understanding of the hormetic effect of Cd in wheat, which would be beneficial for improving the quality of hazard and risk assessments.

Investigating the potential risk of cadmium exposure on seizure severity and anxiety-like behaviors through the ferroptosis pathway in epileptic mice: An integrated multi-omics approach

Cadmium, a toxic heavy metal from industrial activities, poses a neurotoxic risk, especially to children. While seizures are common in children, the link between cadmium and seizure activity is unclear. Ferroptosis, an iron-dependent cell death, is key in seizure-induced hippocampal damage and related anxiety. This study aims to elucidate these mechanisms and assess the broader implications of cadmium exposure. Our research contributes in three significant areas: Firstly, through a combination of observational studies in long-term cadmium-exposed workers, Mendelian randomization analysis, NHANES analysis, urinary metabolomics, and machine learning analysis, we explored the impact of long-term cadmium exposure on inflammatory cytokines, ferroptosis-related gene expression, and lipid and iron metabolism. Secondly, by harnessing public databases for human disorders and metal-associated gene targets, alongside therapeutic molecular analyses, we identified critical human gene targets for cadmium toxicity in seizures and proposed melatonin as a promising therapeutic agent. Finally, utilizing mouse behavioral assays, T2 MRI, and MRS, we provide evidence of how prolonged cadmium exposure disrupts iron and lipid metabolism in the brain, triggering ferroptosis in the hippocampus.

Proteomic analysis of toxic effects of short-term cadmium exposure on goat livers.

Food safety is closely related to environmental pollution. It is worth noting that the long-term accumulation of Cd, a toxic heavy metal, in animals may pose a threat to human health through food chain. Previous studies have found that Cd exposure may cause liver metabolic disorders of black goats, but the mechanism of its impact on liver proteome of goats has not been widely studied. Therefore, in this study, ten male goats (Nubian black goat × native black goat) were exposed to Cd via drinking water containing CdCl2 (20mg Cd·kg-1·BW) for 30days (five male goats per group). Blood physiology and liver antioxidant indices in black goats were determined and differentially expressed proteins (DEPs) in the livers of Cd-exposed goats were profiled by using TMT-labelled proteomics. It was found that plasma Hb and RBC levels as well as PCV values were decreased, liver SOD, GSH-Px, T-AOC and CAT levels were decreased, and MDA level was increased in Cd-treated goats, and 630 DEPs (up 326, down 304) in the livers of Cd-treated goats. Proteomics analysis revealed that Cd exposure affected glutathione metabolism and drug metabolism-cytochrome P450. We identified GP×2, GSTM3, and TBXAS1 as potential protein markers of early Cd toxicity in goats. This study provided theoretical basis for early diagnosis of Cd poisoning in goats.

Gender Differences in the Effects of Cadmium Exposure on Hematological Parameters in Wistar Rats

This study aims to investigate the gender dimorphism in cadmium exposure on hematological parameters in male and female Wistar rats. Twenty Wistar rats (120g-150g) were divided into four groups: male control, male cadmium-treated, female control, and female cadmium-treated. Cadmium chloride (50 mg/kg) was administered orally to the experimental groups for 45 days. Hematological parameters were analyzed using an auto hematological analyzer. Data were statistically evaluated using two-way ANOVA with significance set at p < 0.05. Cadmium exposure significantly increased white blood cell (WBC) counts in male rats compared to controls, with notable decrease in neutrophils and an increase in lymphocytes. Female rats showed significant increase in monocyte and basophil levels. Furthermore, red blood cell (RBC) parameters showed significant reductions in hemoglobin concentration, mean corpuscular volume (MCV), and mean corpuscular hemoglobin (MCH) in female cadmium-treated rats. No significant effects were observed on platelet count or distribution width in both male and female rats. The study concluded there are gender-specific hematological alterations due to cadmium exposure in Wistar rats. These findings underscore the need for gender-specific approach in the understanding and amelioration of cadmium toxicity.

Cadmium (Third Edition) (Chemicals and Contaminants).

Exposure to cadmium tends to be higher in Japan than in other countries due to the wide spreading of ore deposits and many mines throughout Japan. The proximal tubule of the kidney is recognized as the most susceptible site to be affected by cadmium exposure. Food Safety Commission of Japan (FSCJ) considered it appropriate to investigate studies of the effects of cadmium intake on renal proximal tubular function using urinary β2-microglobulin concentration of 1,000 μg/g creatinine as a criterion for the dysfunction. Based on these epidemiological studies, FSCJ established a tolerable weekly intake (TWI) of 7 µg/kg bw per week for cadmium. This value is derived from the results of actual dietary surveys and urinary β2-microglobulin concentrations in Japan, and not from the results of application of blood or urinary cadmium levels to theoretical models. Therefore, no uncertainty factor is required. The estimated dietary intake of cadmium in 2022 was 2.03 µg/kg bw per week, approximately 30% of the TWI of 7 µg/kg bw per week. Therefore, it is unlikely that dietary cadmium intake in the general Japanese population would cause adverse health effects.

Cadmium Exposure and Noncommunicable Diseases in Environmentally Exposed Brazilian Population: Cross-Sectional Study without Association of GSTP1 Polymorphism.

Cadmium (Cd) is a toxic metal which is harmful to humans and the environment. Cd levels and adverse effects may be associated with genetic polymorphisms in genes involved in its toxicokinetics. This study investigated Cd levels in 198 residents of a condominium in Rio de Janeiro, Brazil, built on industrial steel slag waste and the influence of glutathione S-transferase pi isoform 1 (GSTP1) rs1695 A>G polymorphism. Polymorphism was genotyped using a validated TaqMan assay; Cd levels were measured in blood (BCd) and urine (UCd) by graphite furnace atomic absorption spectrometry. Associations were evaluated by multiple logistic regression, odds ratios (ORs), and 95% confidence intervals (CIs). The mean Cd levels were 0.70 ± 0.20 µg L-1 (BCd), 0.58 ± 0.57 µg L-1 (UCd), and 0.61 ± 0.65 µg g-1 in urine corrected by creatinine (UcCd), and the Cd results were above tolerable levels (BCd > 0.5 µg L-1) in 87.4% of subjects. Higher blood Cd levels (>0.69 µg L-1) were associated with respiratory disease (OR = 2.4; 95%CI = 1.2-5.0), as almost 30% of people with respiratory diseases had higher Cd levels. The GSTP1 rs1695AA genotype frequency was 38.1%, and there were no significant differences between the SNP and Cd levels. High Cd levels and a high prevalence of diseases highlight the importance of implementing public policies and the continuous monitoring of this at-risk population.

Association of combined lead, cadmium, and mercury with systemic inflammation.

Exposure to environmental metals has been increasingly associated with systemic inflammation, which is implicated in the pathogenesis of various chronic diseases, including those with neurodegenerative aspects. However, the complexity of exposure and response relationships, particularly for mixtures of metals, has not been fully elucidated. This study aims to assess the individual and combined effects of lead, cadmium, and mercury exposure on systemic inflammation as measured by C-reactive protein (CRP) levels, using data from the National Health and Nutrition Examination Survey (NHANES) 2017-2018. We employed Bayesian Kernel Machine Regression (BKMR) to analyze the NHANES 2017-2018 data, allowing for the evaluation of non-linear exposure-response functions and interactions between metals. Posterior Inclusion Probabilities (PIP) were calculated to determine the significance of each metal's contribution to CRP levels. The PIP results highlighted mercury's significant contribution to CRP levels (PIP = 1.000), followed by cadmium (PIP = 0.6456) and lead (PIP = 0.3528). Group PIP values confirmed the importance of considering the metals as a collective group in relation to CRP levels. Our BKMR analysis revealed non-linear relationships between metal exposures and CRP levels. Univariate analysis showed a flat relationship between lead and CRP, with cadmium having a positive relationship. Mercury exhibited a U-shaped association, indicating both low and high exposures as potential risk factors for increased inflammation. Bivariate analysis confirmed this relationship when contaminants were combined with lead and cadmium. Analysis of single-variable effects suggested that cadmium and lead are associated with higher values of the h function, a flexible function that takes multiple metals and combines them in a way that captures the complex and potentially nonlinear relationship between the metals and CRP. The overall exposure effect of all metals on CRP revealed that exposures below the 50th percentile exposure level are associated with an increase in CRP levels, while exposures above the 60th percentile are linked to a decrease in CRP levels. Our findings suggest that exposure to environmental metals, particularly mercury, is associated with systemic inflammation. These results highlight the need for public health strategies that address the cumulative effects of metal exposure and reinforce the importance of using advanced statistical methods to understand the health impact of environmental contaminants. Future research should focus on the mechanistic pathways of metal-induced inflammation and longitudinal studies to ascertain the long-term effects of these exposures.

Acute waterborne cadmium exposure induces liver ferroptosis in Channa argus

The impact of cadmium (Cd) toxicity on fish liver injury has received much attention in recent years. Currently, autophagy, apoptosis and endoplasmic reticulum stress were reported in Cd exposed fish liver, and if there are other mechanisms (such as ferroptosis) and relevant signaling pathways involved in fish remains unknown. An experiment was conducted to investigate Cd toxicity in Channa argus (Cantor, 1842) exposed to 0, 1.0, and 2.0 mg Cd/L of water for 96 h. Cd disrupted the structure of mitochondria in the liver. Besides, Cd induced ferroptosis by significantly increasing the level of Fe2+, ROS, MDA and significantly decreasing the level of Ferritin, GSH, GSH-Px, GPX4, GST and SOD (p < 0.05 in all cases). In addition, the mRNA expression of ferroptosis related genes, gpx4 and slc7a11, were significantly downregulated by Cd. Moreover, Cd exposure significantly inhibited the Nrf2/Keap1 signaling pathway, one of the pathways involved in ferroptosis, by upregulating the mRNA levels of keap1a and keap1b, and downregulating the mRNA levels of nrf2 and its target genes (ho-1, nqo1 and cat). Cd exposure also caused extensive accumulation of vacuoles and lipid droplets in liver, as well as an increase in triglyceride content. Cd significantly affected lipid metabolism related enzyme activity and gene expression, which were also regulated by Nrf2/Keap1 signaling pathway. In summary, these results indicate that ferroptosis is a mechanism in waterborne Cd exposed fish liver injury via the Nrf2/Keap1 signaling pathway and the Cd induced hepatic steatosis is also modulated by Nrf2/Keap1 pathway at the whole-body level in fish. These findings provide new insights into the fish liver injury and molecular basis of Cd toxicity.

Cadmium exposure induces skeletal muscle insulin resistance through the reactive oxygen species-mediated PINK1/Parkin pathway

Epidemiological studies have suggested a positive association between environmental cadmium (Cd) exposure and type 2 diabetes mellitus (T2DM). Skeletal muscle insulin resistance (IR) plays a critical role in the pathogenesis of T2DM. This study aimed to investigate the effects of chronic low-level Cd exposure on skeletal muscle IR and its potential mechanism. Rats were exposed to drinking water containing 2 or 10 mg/L Cd for 24 weeks. Differentiated L6 myotubes were treated with Cd for 72 h. Immunofluorescence, flow cytometry assay, RNA-sequencing, and Seahorse analysis were conducted to determine the effects of Cd and its underlying mechanism on relevant parameters, including insulin sensitivity, glucose uptake, oxidative stress, mitophagy, and mitochondrial function in skeletal muscle and L6 myotubes. N-acetyl-cysteine (NAC), a scavenger of reactive oxygen species (ROS), and mitophagy inhibitor Cyclosporin A (CsA) were used to confirm the role of oxidative stress in mitophagy and mitochondrial dysfunction caused by Cd. We found that rats exposed to 10 mg/L Cd exhibited hyperglycemia and skeletal muscle IR. Cd markedly increased IRS-1 phosphorylation at Ser612, while decreased levels of phosphorylated PI3K, Akt, AS160, inhibited GLUT4 translocation and glucose uptake. Mechanistically, Cd increased the intracellular ROS, hydrogen peroxide, and malondialdehyde levels and decreased antioxidase activity in L6 myotubes. Furthermore, Cd upregulated the mRNA and protein levels of LC3II/I, PINK1, and Parkin. In addition, Cd induced the formation of mitophagosomes, reduced the mitochondrial membrane potential, decreased the adenosine triphosphate content, and impaired the mitochondrial respiratory capacity. Strikingly, NAC ameliorated oxidative stress, excessive mitophagy, and the associated reduction in myotube insulin sensitivity, while inhibition of mitophagy by CsA alleviated skeletal muscle IR. In conclusion, this study reveals a previously unrecognized mechanism that chronic low-level Cd exposure may induce mitophagy by activating the PINK1/Parkin signal pathway by increasing ROS, thus causing skeletal muscle IR and elevated blood glucose.

Evaluating combined effects of chronic, low-dose exposures of cadmium (CLEC) and hyperglycemia on insulin signaling dysfunction in a hepatocellular model

The pathophysiological effects of chronic heavy metal exposures on human health remains uncertain. In this study, we developed a novel chronic, low-dose exposure of Cadmium (CLEC) model using the hepatocellular cell lines, HepG2 and HUH7. We modulated cell culture conditions to mimic human normoglycemic (5.6 mM) and hyperglycemic (15 mM) states with concomitant cadmium (Cd) exposures for 24 weeks. CLEC cells undergo non-trivial alterations in glucose signaling and metabolic characteristics within our model. We observe elevated baseline reactive oxygen species (ROS) production and decreased 2-NBDG uptake indicative of glucose metabolic dysfunction. Additionally, induction of metallothionein (MT) expression, increased activation of Akt signaling (via phosphorylation) and reduced IRS-2 protein expression are observed in CLEC cells. Cell line specific changes are observed with HepG2 showing a much higher MT gene induction compared to HUH7 cell line which impacts glucose metabolic dysfunction. Hyperglycemic culture conditions (representing type II diabetes) significantly modulate CLEC effects on cells. In conclusion, pathophysiologically relevant models of chronic heavy metal exposures are urgently needed to gain an in-depth, mechanistic understanding of the long-term impacts of toxic metals (e.g., Cd) on human metabolic health.

Transfer from ciliate to zebrafish: Unveiling mechanisms and combined effects of microplastics and heavy metals

The impacts and toxicological mechanisms of microplastics (MPs) or heavy metals on aquatic ecosystems have been the subject of extensive research and initial understanding. However, the combined toxicity of co-pollutants on organisms and cumulative toxic effects along the food chain are still underexplored. In this study, the ciliate protozoan Paramecium caudatum and zebrafish Danio rerio were used to represent the microbial loop and the higher trophic level, respectively, to illustrate the progressive exposure of MPs and cadmium (Cd2+). The findings indicate that MPs (ca. 1 ×105 items/L) containing with Cd2+ (below 0.1 µg/L) could permeate the bodies of zebrafish through trophic levels after primary ingestion by ciliates. This could cause adverse effects on zebrafish, including alterations in bioindicators (total sugar, triglycerides, lactate, and glycogen) associated with metabolism, delayed hepatic development, disruption of intestinal microbiota, DNA damage, inflammatory responses, and abnormal cellular apoptosis. In addition, the potential risks associated with the transfer of composite pollutants through the microbial loop into traditional food chain were examined, offering novel insights on the evaluation of the ecological risks associated with MPs. As observed, understanding the bioaccumulation and toxic effects of combined pollutants in zebrafish holds crucial implications for food safety and human health.

Cadmium Exposure and Risk of Pancreatic Cancer: A Protocol of Systematic Review and Meta-analysis

Background: Pancreatic cancer is a devastating disease with a poor prognosis, and its etiology involves a complex interplay of genetic, environmental, and lifestyle factors. Among environmental factors, cadmium, a toxic heavy metal, has been implicated in carcinogenesis and is found in various industrial processes, tobacco smoke, and certain foods. Previous studies examining the association between cadmium exposure and pancreatic cancer risk have reported inconsistent findings, necessitating a systematic review and meta-analysis to clarify this relationship. Methods: A systematic search was conducted following PRISMA guidelines to identify relevant studies from electronic databases, including PubMed, Embase, Web of Science, Cochrane Library, Scopus, and Google Scholar. Eligible studies included observational designs (cohort, case-control, cross-sectional) that investigated the association between cadmium exposure and pancreatic cancer risk in human populations. Data extraction, risk of bias assessment, and meta-analysis were conducted using established protocols. Subgroup analyses were performed based on study characteristics and exposure assessment methods. Results: The systematic review and meta-analysis included a comprehensive assessment of the existing literature on cadmium exposure and pancreatic cancer risk. Pooled analysis of eligible studies revealed a potential association between cadmium exposure and an increased risk of pancreatic cancer. However, the magnitude and consistency of this association varied across studies, highlighting the complexity of environmental exposures and their impact on cancer risk. Subgroup analyses and sensitivity analyses were conducted to explore sources of heterogeneity and assess the robustness of the results. Conclusion: This systematic review and meta-analysis contribute to the current understanding of the relationship between cadmium exposure and pancreatic cancer risk. While the findings suggest a potential association, further research is needed to elucidate the underlying mechanisms and clarify the role of cadmium in pancreatic carcinogenesis. These results underscore the importance of environmental risk factors in cancer development and highlight the need for public health interventions aimed at reducing cadmium exposure and improving cancer prevention strategies.

Screening of differentially expressed RNAs and identifying a ceRNA axis during cadmium-induced oxidative damage in pancreatic β cells

Cadmium, a common metal pollutant, has been demonstrated to induce type 2 diabetes by disrupting pancreatic β cells function. In this study, transcriptome microarray was utilized to identify differential gene expression in oxidative damage to pancreatic β cells following cadmium exposure. The results indicated that a series of mRNAs, LncRNAs, and miRNAs were altered. Of the differentially expressed miRNAs, miR-29a-3p exhibited the most pronounced alteration, with an 11.62-fold increase relative to the control group. Following this, the target gene of miR-29a-3p was identified as Col3a1 through three databases (miRDB, miRTarbase and Tarbase), which demonstrated a decrease across the transcriptome microarray. The upstream target gene of miR-29a-3p was identified as NONMMUT036805, with decreased expression observed in the microarray. Finally, the expression trend of NONMMUT036805/miR-29a-3p/Col3a1 was reversed following NAC pretreatment. This was accompanied by a reduction in oxidative damage indicators, MDA/ROS/GSH-Px appeared to be negatively affected to varying degrees. In conclusion, this study has demonstrated that multiple RNAs are altered during cadmium exposure-induced oxidative damage in pancreatic β cells. The NONMMUT036805/miR-29a-3p/Col3a1 axis has been shown to be involved in this process, which provides a foundation for the identification of potential targets for cadmium toxicity intervention.