-
Environmental Health Perspectives Feb 2010We provide an update of the issues surrounding health risk assessment of exposure to cadmium in food. (Review)
Review
OBJECTIVES
We provide an update of the issues surrounding health risk assessment of exposure to cadmium in food.
DATA SOURCES
We reviewed epidemiologic studies published between 2004 and 2009 concerning the bioavailability of cadmium in food, assessment of exposure, and body burden estimate, along with exposure-related effects in nonoccupationally exposed populations.
DATA EXTRACTION AND SYNTHESIS
Bioavailability of ingested cadmium has been confirmed in studies of persons with elevated dietary exposure, and the findings have been strengthened by the substantial amounts of cadmium accumulated in kidneys, eyes, and other tissues and organs of environmentally exposed individuals. We hypothesized that such accumulation results from the efficient absorption and systemic transport of cadmium, employing multiple transporters that are used for the body's acquisition of calcium, iron, zinc, and manganese. Adverse effects of cadmium on kidney and bone have been observed in environmentally exposed populations at frequencies higher than those predicted from models of exposure. Increasing evidence implicates cadmium in the risk of diseases that involve other tissues and organ systems at cadmium concentrations that do not produce effects on bone or renal function.
CONCLUSIONS
Population data raise concerns about the validity of the current safe intake level that uses the kidney as the sole target in assessing the health risk from ingested cadmium. The data also question the validity of incorporating the default 5% absorption rate in the threshold-type risk assessment model, known as the provisional tolerable weekly intake (PTWI), to derive a safe intake level for cadmium.
Topics: Bone and Bones; Cadmium; Environmental Exposure; Humans; Kidney; Risk Assessment
PubMed: 20123617
DOI: 10.1289/ehp.0901234 -
Ecotoxicology and Environmental Safety Oct 2022Cadmium (Cd) is a type of high-risk heavy metal that can damage organs such as the liver, but its mechanism is not yet clear. Ferroptosis is a newly discovered mode of...
Cadmium (Cd) is a type of high-risk heavy metal that can damage organs such as the liver, but its mechanism is not yet clear. Ferroptosis is a newly discovered mode of regulatory cell death. We explored whether ferroptosis is involved in Cd-induced liver damage and the underlying mechanism. Our research showed that Cd induced liver damage by inducing ferroptosis, and the use of ferroptosis inhibitors reduced the degree of liver damage. Moreover, the occurrence of ferroptosis was accompanied by the activation of the PERK-eIF2α-ATF4-CHOP signaling pathway, and inhibiting endoplasmic reticulum (ER) stress reduced ferroptosis demonstrating that ferroptosis induced by Cd is dependent on ER stress. In addition, chloroquine, a common autophagy inhibitor, mitigated ferroptosis caused by Cd exposure. Then, the iron chelator deferoxamine reduced Cd-induced lipid peroxidation and cell death, demonstrating that the iron regulation disorder caused by ferritin phagocytosis contributes to the Cd-induced ferroptosis. In conclusion, our results show that Cd-induced liver toxicity is accompanied by ferroptosis, which contributes to Cd inducing oxidative stress to trigger autophagy and ER stress to promote the process of ferroptosis.
Topics: Autophagy; Cadmium; Chloroquine; Deferoxamine; Endoplasmic Reticulum Stress; Ferritins; Ferroptosis; Humans; Iron; Iron Chelating Agents; Liver Diseases
PubMed: 36183427
DOI: 10.1016/j.ecoenv.2022.114123 -
Environment International Apr 2021Cadmium is known as an environmental pollutant that contributes to pancreatic damage and the pathogenesis of diabetes. However, less attention has been devoted to...
Cadmium is known as an environmental pollutant that contributes to pancreatic damage and the pathogenesis of diabetes. However, less attention has been devoted to elucidating the mechanisms underlying Cd-induced pancreatic β-cell dysfunction and the role of Cd toxicity in the development of diabetes. In this study, we demonstrated that exposure to Cd caused remarkable pancreatic β-cell dysfunction and death, both in vitro and in vivo. Lipidomic analysis of Cd-exposed pancreatic β-cells using high-resolution mass spectrometry revealed that Cd exposure altered the profile and abundance of lipids. Cd exposure induced intracellular lipid accumulation, promoted lipid biogenesis, elevated pro-inflammatory lipid contents and inhibited lipid degradation. Furthermore, Cd exposure upregulated the expression levels of TNF-α, IL-1β and IL-6 in pancreatic β-cells and elevated the TNF-α, IL1-β and IL-6 levels in the serum and pancreas. Taken together, the results of our study demonstrated that environmental relevant Cd exposure causes pro-inflammatory lipids elevation and insulin secretion dysfunction in β-cells and hence exaggerates diabetes development. Combined exposure to environmental hazardous chemicals might markedly increase the probability of developing diabetes in humans. This study provides new metabolic and pharmacological targets for antagonizing Cd toxicity.
Topics: Cadmium; Diabetes Mellitus; Humans; Insulin-Secreting Cells; Lipid Metabolism; Pancreas
PubMed: 33508533
DOI: 10.1016/j.envint.2021.106406 -
Ecotoxicology (London, England) Nov 2022Different factors, such as starvation and metal exposure, may affect development and cause oxidative stress in insects. Some host plants may contain a high concentration...
Different factors, such as starvation and metal exposure, may affect development and cause oxidative stress in insects. Some host plants may contain a high concentration of cadmium due to their hyperaccumulating property. The negative effects of metals and hunger may be manifested by low availability of energetic substrates. This study aimed to assess whether the insect population with a history of long metal exposure may better manage metal stress or/and starvation at different developmental stages, with the use of energetic substrates. Two strains of Spodoptera exigua model organism were tested: control strain and cadmium strain (treated continuously for over 200 generations with subtoxic amounts of cadmium). The effects of different factors, individually and in combination, on the tested strains were assessed, first by determining the body weight of larvae and pupae and then by estimating the concentration of biomolecules (proteins, carbohydrates, lipids, or glycogen) in the 4th and 5th larval stages and in pupae, and the total antioxidant capacity and lipid peroxidation level in the 4th larval stage. Compared to control strain, cadmium strain individuals exhibited changes in the concentration of soluble carbohydrates and protein. This was partly related to earlier 1-day starvation. In particular, changes in carbohydrate concentration seemed to be a sensitive biomarker of metal stress, independent of the age of individuals and period of starvation. However, the increase in the total antioxidant capacity and the concentration of lipid peroxidation products in the 4th larval stage under the effect of cadmium was dependent on strain origin.
Topics: Humans; Animals; Cadmium; Spodoptera; Antioxidants; Oxidative Stress; Larva; Carbohydrates
PubMed: 36173496
DOI: 10.1007/s10646-022-02588-6 -
Medicine Mar 2016Several observational studies have investigated the relation between cadmium exposure and risk of any fracture. However, the results from epidemiological studies for the... (Meta-Analysis)
Meta-Analysis Review
Several observational studies have investigated the relation between cadmium exposure and risk of any fracture. However, the results from epidemiological studies for the association are inconsistent.We conducted a meta-analysis to evaluate the relationship between cadmium exposure and risk of any fracture. The pertinent studies were identified by a search of PubMed and Embase databases from 1966 to June 2015.Seven articles involving 21,941 fracture cases and 504,346 participants were included. The meta-analysis showed that the pooled relative risk of any fracture for the highest versus lowest category of cadmium concentration was 1.30 (95% confidence interval = 1.13-1.49). In subgroup analyses, the significant association remained consistent when stratified by study type, geographical region, method of cadmium exposure assessment, and gender.Our meta-analysis showed that a high cadmium exposure may be a risk factor for any fracture. However, this result should be interpreted cautiously because of the heterogeneity among studies and existence of publication bias. Additional large, high-quality prospective studies are needed to evaluate the association between cadmium exposure and the risk of development of fracture.
Topics: Cadmium; Fractures, Bone; Humans; Observational Studies as Topic
PubMed: 26962791
DOI: 10.1097/MD.0000000000002932 -
Cells Nov 2022Cadmium is a heavy toxic metal with unknown biological functions in the human body. Over time, cadmium accretion in the different visceral organs (liver, lungs, kidney,... (Review)
Review
Cadmium is a heavy toxic metal with unknown biological functions in the human body. Over time, cadmium accretion in the different visceral organs (liver, lungs, kidney, and testis) is said to impair the function of these organs, which is associated with a relatively long biological half-life and a very low rate of excretion. Recently studies have revealed that the testes are highly sensitive to cadmium. In this review, we discussed the adverse effect of cadmium on the development and biological functions of the testis. The Sertoli cells (SCs), seminiferous tubules, and Blood Testis Barrier are severely structurally damaged by cadmium, which results in sperm loss. The development and function of Leydig cells are hindered by cadmium, which also induces Leydig cell tumors. The testis's vascular system is severely disturbed by cadmium. Cadmium also perturbs the function of somatic cells and germ cells through epigenetic regulation, giving rise to infertile or sub-fertile males. In addition, we also summarized the other findings related to cadmium-induced oxidative toxicity, apoptotic toxicity, and autophagic toxicity, along with their possible mechanisms in the testicular tissue of different animal species. Consequently, cadmium represents a high-risk factor for male fertility.
Topics: Animals; Male; Humans; Cadmium; Epigenesis, Genetic; Semen; Testis; Fertility
PubMed: 36429028
DOI: 10.3390/cells11223601 -
Environmental Research Feb 2023Cadmium is a heavy metal with carcinogenic properties, highly prevalent in industrialized areas worldwide. Prior reviews evaluating whether cadmium influences breast... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Cadmium is a heavy metal with carcinogenic properties, highly prevalent in industrialized areas worldwide. Prior reviews evaluating whether cadmium influences breast cancer have been inconclusive and not reflected several recent studies.
OBJECTIVE
To evaluate the association between cadmium exposure and female breast cancer incidence, with an emphasis on separately estimating dietary vs. airborne vs. biomarker measures of cadmium and studies published until October 2022.
METHODS
We evaluated risk of bias using set criteria and excluded one study judged to have high risk based on self-report of breast cancer and insufficient adjustment. We conducted a random effects meta-analysis of epidemiological studies, including subgroups by exposure route and by menopausal status.
RESULTS
A total of 17 studies were eligible for our meta-analysis. Only 2 studies addressed airborne cadmium directly. Breast cancer risk was elevated in women exposed to higher levels of cadmium across all studies - pooled odds ratio: 1.13 (95% confidence interval: 1.00, 1.28), with notable heterogeneity between studies (I = 77%). When examining separately by exposure route, dietary cadmium was not linked with an elevated risk - (OR: 1.05; 95%CI: 0.91, 1.21; I = 69%), consistent with prior reviews, but biomarker-based studies showed an elevated but non-significant pooled measure (OR: 1.37; 95%CI: 0.96, 1.94; I = 84%). We did not observe any clear patterns of different risk by menopausal status.
CONCLUSION
Findings from our meta-analysis suggest that exposure to higher cadmium increases the risk of breast cancer in women, but with remaining questions about whether non-dietary exposure may be more risky or whether residual confounding by constituents of tobacco smoke may be at play.
Topics: Female; Humans; Breast Neoplasms; Metals, Heavy; Cadmium; Risk; Breast
PubMed: 36563983
DOI: 10.1016/j.envres.2022.115109 -
Acta Biochimica Polonica 2012Cadmium is a toxic and carcinogenic heavy metal that nowadays constitutes a serious environmental health problem. The aim of this study is to review the effects of... (Review)
Review
Cadmium is a toxic and carcinogenic heavy metal that nowadays constitutes a serious environmental health problem. The aim of this study is to review the effects of cadmium on selected inflammatory mediators and markers, such as NF-κB and AP-1 transcription factors, IL-6, TNF-α, IL-1β cytokines, IL-8 or MIP-2 chemokine, MPO, iNOS, MMPs and COX-2 enzymes, PGE(2) (product of COX-2 enzyme), ICAM-1, VCAM-1 and PECAM-1 adhesion molecules, and CRP. The research strategy identified articles available in Medline, published between 1998 and 2012; we included both in vivo and in vitro studies carried out on humans and rodents. Most of the reviewed research findings suggest that cadmium in micromolar concentrations (especially in the 1-10 μM range) causes up-regulation of the mediators and markers of inflammation, and appears to have pro-inflammatory properties. However, it is worth mentioning that a contradictory or even opposite hypothesis exists, which suggests cadmium to be an anti-inflammatory factor. Further research including detailed histological analyses should solve this discrepancy. Nevertheless, it appears that the main reason for these contradictory findings is the experimental setup: different biological systems analyzed and different doses of cadmium applied.
Topics: Anti-Inflammatory Agents; Biomarkers; Cadmium; Carcinogens, Environmental; Cytokines; Environmental Health; Humans; Inflammation; Inflammation Mediators; MEDLINE
PubMed: 23240106
DOI: No ID Found -
Nihon Eiseigaku Zasshi. Japanese... 2018Cadmium is a nonessential heavy metal and an industrial and environmental pollutant. It has been known that cadmium must enter cells to cause damage. To understand the... (Review)
Review
Cadmium is a nonessential heavy metal and an industrial and environmental pollutant. It has been known that cadmium must enter cells to cause damage. To understand the transport systems responsible for cadmium entry into cells, it is important to determine the precise mechanisms underlying cadmium toxicity. Numerous studies have sought to unravel the exact pathways by which cadmium enters various cells and the mechanisms by which it causes toxicity in the organs of human and animals. The purpose of this review is to present the progress made regarding the mechanisms of cadmium transport in various cells and the mechanisms underlying cadmium toxicity in organs.
Topics: Animals; Apoptosis; Biological Transport; Cadmium; Calcium Channels; Carrier Proteins; Cells; Endoplasmic Reticulum Stress; Environmental Pollutants; Humans; Metallothionein; Mice; Repressor Proteins; Transcription Factors
PubMed: 30270291
DOI: 10.1265/jjh.73.269 -
PeerJ 2023Dietary ingestion is the main route of exposure to hazardous contaminants in land animals. Cadmium, a high-profile toxic metal, affects living systems at different...
Dietary ingestion is the main route of exposure to hazardous contaminants in land animals. Cadmium, a high-profile toxic metal, affects living systems at different organismal levels, including major storage organs (liver, kidneys), key organs for species survival (gonads), and epigenetic networks regulating gene expression. 5-methylcytosine (5mC) is the most common and best-characterized epigenetic mark among different modified nucleosides in DNA. This important player in methylation-driven gene expression is impacted by cadmium in sentinel terrestrial vertebrates. However, limited information exists regarding its impact on macroinvertebrates, especially land snails commonly used as (eco)toxicological models. We first investigate the methylomic effects of dietary cadmium given as cadmium nitrate on terrestrial mollusks. Mature specimens of the common brown garden snail, , were continuously exposed for four weeks to environmentally-relevant cadmium levels. We determined global genomic DNA methylation in hepatopancreas and ovotestis, as well as changes in the methylation status of CG pairs at the 5' region close to the transcription site of gene encoding the Cd-selective metallothionein (Cd-MT). Weight gain/loss, hypometabolism tendency, and survival rates were also assessed. Although this exposure event did not adversely affect survival, gastropods exposed to the highest Cd dose revealed a significant reduction in body weight and a significant increase in hypometabolic behavior. The hepatopancreas, but not the ovotestis, displayed significant hypermethylation, but only for the aforementioned specimens. We also found that the 5' end of the gene was unmethylated in both organs and its methylation status was insensitive to cadmium exposure. Our results are important since they provide scientists, for the first time, with quantitative data on DNA methylation in gastropod ovotestis and refine our understanding of Cd epigenetic effects on terrestrial mollusks.
Topics: Animals; Cadmium; DNA Methylation; Hepatopancreas; Cadmium Compounds
PubMed: 37073276
DOI: 10.7717/peerj.15032