Cadmium exposures and deteriorations of cognitive abilities: estimation of a reference dose for mixture risk assessments based on a systematic review and confidence rating

Chatterjee, Mousumi; Kortenkamp, Andreas

doi:10.1186/s12940-022-00881-9

Cited by 15 publications

(6 citation statements)

References 41 publications

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“…The dominant groups in the zebrafish gut flora included Firmicutes and Proteobacteria , and the results indicated that the proportion of Firmicutes decreased while the proportion of Proteobacteria increased in zebrafish larvae after 7 days of Cd exposure. The above results were consistent with those of some existing studies [ 7 , 22 ].…”

Section: Discussionsupporting

confidence: 94%

“…The effects on the central nervous system could pass through the gut–brain axis [ 15 , 16 ]. Dysbiosis of the gut microflora can cause changes in the concentrations of metabolites, which can induce various diseases [ 17 , 18 , 19 , 20 , 21 , 22 ]. In this study, we established a zebrafish model, exposed it to environmentally relevant concentrations of Cd (5 µg/L), and examined the relevant indicators.…”

Section: Discussionmentioning

confidence: 99%

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Effects of Ecologically Relevant Concentrations of Cadmium on the Microbiota, Short-Chain Fatty Acids, and FFAR2 Expression in Zebrafish

Yang

Zhang

et al. 2023

Metabolites

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Exposure to cadmium (Cd) can affect neurodevelopment and results in increased potential of developing neurodegenerative diseases during the early developmental stage of organisms, but the mechanisms through which exposure to environmentally relevant concentrations of Cd lead to developmental neurotoxicity remain unclear. Although we know that microbial community fixations overlap with the neurodevelopmental window during early development and that Cd-induced neurodevelopmental toxicity may be related to the disruption of microorganisms during early development, information on the effects of exposure to environmentally relevant Cd concentrations on gut microbiota disruption and neurodevelopment is scarce. Therefore, we established a model of zebrafish exposed to Cd (5 µg/L) to observe the changes in the gut microbiota, SCFAs, and free fatty acid receptor 2 (FFAR2) in zebrafish larvae exposed to Cd for 7 days. Our results indicated that there were significant changes in the gut microbial composition due to the exposure to Cd in zebrafish larvae. At the genus level, there were decreases in the relative abundances of Phascolarctobacterium, Candidatus Saccharimonas, and Blautia in the Cd group. Our analysis revealed that the acetic acid concentration was decreased (p > 0.05) while the isobutyric acid concentration was increased (p < 0.05). Further correlation analysis indicated a positive correlation between the content of acetic acid and the relative abundances of Phascolarctobacterium and Candidatus Saccharimonas (R = 0.842, p < 0.01; R = 0.767, p < 0.01), and a negative correlation between that of isobutyric acid and the relative abundance of Blautia glucerasea (R = −0.673, p < 0.05). FFAR2 needs to be activated by SCFAs to exert physiological effects, and acetic acid is its main ligand. The FFAR2 expression and the acetic acid concentration were decreased in the Cd group. We speculate that FFAR2 may be implicated in the regulatory mechanism of the gut–brain axis in Cd-induced neurodevelopmental toxicity.

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Section: Discussionsupporting

confidence: 94%

Section: Discussionmentioning

confidence: 99%

Effects of Ecologically Relevant Concentrations of Cadmium on the Microbiota, Short-Chain Fatty Acids, and FFAR2 Expression in Zebrafish

Yang

Zhang

et al. 2023

Metabolites

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“…The widespread occurrence of the pollutant cadmium and the inability of humans exposed to this heavy metal to safely remove it from their body explains the broad interest of scientists and physicians in the health hazards possibly caused by cadmium ( Table 5 ) [ 263 , 268 , 269 , 274 , 275 , 276 , 277 , 278 , 279 , 280 , 281 ].…”

Section: Cadmiummentioning

confidence: 99%

“…Food, water, and air contaminated with environmental cadmium represents the major health hazard for exposed humans ( Table 5 ) [ 263 , 268 , 269 , 274 , 275 , 276 , 277 , 278 , 279 , 280 , 281 ]. As cadmium is not biodegradable in the human body, it accumulates and exerts its toxic effects on a variety of organs, which leads to functional impairment including the liver with increased LTs in one study [ 280 ] but not in two others [ 269 , 279 ].…”

Section: Cadmiummentioning

confidence: 99%

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Copper, Iron, Cadmium, and Arsenic, All Generated in the Universe: Elucidating Their Environmental Impact Risk on Human Health Including Clinical Liver Injury

Teschke

2024

IJMS

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Humans are continuously exposed to various heavy metals including copper, iron, cadmium, and arsenic, which were specifically selected for the current analysis because they are among the most frequently encountered environmental mankind and industrial pollutants potentially causing human health hazards and liver injury. So far, these issues were poorly assessed and remained a matter of debate, also due to inconsistent results. The aim of the actual report is to thoroughly analyze the positive as well as negative effects of these four heavy metals on human health. Copper and iron are correctly viewed as pollutant elements essential for maintaining human health because they are part of important enzymes and metabolic pathways. Healthy individuals are prepared through various genetically based mechanisms to maintain cellular copper and iron homeostasis, thereby circumventing or reducing hazardous liver and organ injury due to excessive amounts of these metals continuously entering the human body. In a few humans with gene aberration, however, liver and organ injury may develop because excessively accumulated copper can lead to Wilson disease and substantial iron deposition to hemochromatosis. At the molecular level, toxicities of some heavy metals are traced back to the Haber Weiss and Fenton reactions involving reactive oxygen species formed in the course of oxidative stress. On the other hand, cellular homeostasis for cadmium and arsenic cannot be provided, causing their life-long excessive deposition in the liver and other organs. Consequently, cadmium and arsenic represent health hazards leading to higher disability-adjusted life years and increased mortality rates due to cancer and non-cancer diseases. For unknown reasons, however, liver injury in humans exposed to cadmium and arsenic is rarely observed. In sum, copper and iron are good for the human health of most individuals except for those with Wilson disease or hemochromatosis at risk of liver injury through radical formation, while cadmium and arsenic lack any beneficial effects but rather are potentially hazardous to human health with a focus on increased disability potential and risk for cancer. Primary efforts should focus on reducing the industrial emission of hazardous heavy metals.

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Urinary Metal Levels, Cognitive Test Performance, and Dementia in the Multi-Ethnic Study of Atherosclerosis

Domingo-Relloso,

McGraw,

Heckbert

et al. 2024

JAMA Netw Open

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ImportanceMetals are established neurotoxicants, but evidence of their association with cognitive performance at low chronic exposure levels is limited.ObjectiveTo investigate the association of urinary metal levels, individually and as a mixture, with cognitive tests and dementia diagnosis, including effect modification by apolipoprotein ε4 allele (APOE4).Design, Setting, and ParticipantsThe multicenter prospective cohort Multi-Ethnic Study of Atherosclerosis (MESA) was started from July 2000 to August 2002, with follow-up through 2018. A total of 6303 MESA participants were included. Data analysis was performed from October 12, 2023, to June 13, 2024.ExposureUrine samples were collected at baseline (2000-2002), and arsenic, cadmium, cobalt, copper, lead, manganese, tungsten, uranium, and zinc levels were measured in 2020-2022.Main Outcomes and MeasuresDigit Symbol Coding (DSC) (n = 3819) (possible score range, 0-133), Cognitive Abilities Screening Instrument (CASI) (n = 3918) (possible score range, 0-100), and Digit Span (DS) (n = 4176) (possible score range, 0-30) cognitive tests were administered in 2010-2012; higher scores of each test indicate increasing levels of positive response.ResultsA total of 6303 participants were followed up for dementia diagnosis through 2018. The median age at baseline was 60 (IQR, 53-70) years, and 3303 participants (52.4%) were female. The median cognitive scores were 51 (IQR, 38-64) for DSC, 90 (IQR, 84-95) for CASI, and 15 (IQR, 12-18) for DS. There were 559 cases of dementia through the follow-up period. Inverse associations with DSC were identified: mean differences in z scores per IQR increase in metal levels were −0.03 (95% CI, −0.07 to 0.00) for arsenic, −0.05 (95% CI, −0.09 to −0.004) for cobalt, −0.05 (95% CI, −0.07 to −0.02) for copper, −0.04 (95% CI, −0.08 to −0.001) for uranium, and −0.03 (95% CI, −0.06 to −0.01) for zinc. Among 1058 APOE4 carriers, manganese was also inversely associated with DSC. The joint mean difference of DSC comparing percentile 95th with the 25th of the 9-metal mixture was −0.30 (95% CI, −0.47 to −0.14) for APOE4 carriers and −0.10 (95% CI, −0.19 to −0.01) for noncarriers. Arsenic, cadmium, cobalt, copper, tungsten, uranium, and zinc were individually associated with dementia, with hazard ratios per IQR of metal ranging from 1.15 (95% CI, 1.03-1.29) for tungsten to 1.46 (95% CI, 1.06-2.02) for uranium. The joint hazard ratio of dementia comparing percentiles 95th with the 25th of the 9-metal mixture was 1.71 (95% CI, 1.24-3.89), with no significant difference by APOE4 status.Conclusions and RelevanceIn this study, participants with higher concentrations of metals in their urine, compared with those with lower concentrations, had worse performance on cognitive tests and greater likelihood of developing dementia. The findings of this multicenter multiethnic cohort study might inform screening and potential interventions for prevention of dementia based on individuals’ metal exposure levels and genetic profiles.

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Cadmium exposures and deteriorations of cognitive abilities: estimation of a reference dose for mixture risk assessments based on a systematic review and confidence rating

Cited by 15 publications

References 41 publications

Effects of Ecologically Relevant Concentrations of Cadmium on the Microbiota, Short-Chain Fatty Acids, and FFAR2 Expression in Zebrafish

Effects of Ecologically Relevant Concentrations of Cadmium on the Microbiota, Short-Chain Fatty Acids, and FFAR2 Expression in Zebrafish

Copper, Iron, Cadmium, and Arsenic, All Generated in the Universe: Elucidating Their Environmental Impact Risk on Human Health Including Clinical Liver Injury

Urinary Metal Levels, Cognitive Test Performance, and Dementia in the Multi-Ethnic Study of Atherosclerosis

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