Effects Of Long-term Cadmium Exposure Research Articles

Metabolic effects of long-term cadmium exposure: an overview.

Cadmium (Cd) is a toxic non-essential heavy metal. Chronic low Cd exposure (CLCE) has been associated with distinct pathologies in many organ systems, including liver and kidney damage, osteoporosis, carcinogenicity, or reproductive toxicity. Currently, about 10% of the global population is at risk of CLCE. It is urgent to find robust and effective biomarkers for early diagnosis of Cd exposure and treatment. Metabolomics is a high-throughput method based on mass spectrometry to study the dynamic changes in a series of endogenous small molecular metabolites (typically < 1000Da) of tissues, cells, or biofluids. It can reflect the rich and complex biochemical changes in the body after exposure to heavy metals, which may be useful in screening biomarkers to monitor exposure to environmental pollutants and/or predict disease risk. Therefore, this review focuses on the changes in metabolic profiles of humans and rodents under long-term Cd exposure from the perspective of metabolomics. Furthermore, the relationship between the disturbance of metabolic pathways and the toxic mechanism of Cd is discussed. All these information will facilitate the development of reliable metabolic biomarkers for early detection and diagnosis of Cd-related diseases.

Cadmium exposure, fasting blood glucose changes, and type 2 diabetes mellitus: A longitudinal prospective study in China

BackgroundCadmium is a recognized human carcinogen, raising global concern for its ubiquitously environmental exposure on public health. Diabetogenic effects of cadmium have been suggested in previous studies, but the longitudinal associations of chronic cadmium exposure with fasting blood glucose changes and type 2 diabetes mellitus have not been fully elucidated. ObjectiveTo investigate the effects of long-term cadmium exposure on the fasting blood glucose changes and type 2 diabetes mellitus risk in a longitudinal prospective study of China. MethodsA total of 3521 urban adults were included as baseline study population from the Wuhan-Zhuhai cohort, and followed up three years later. Urinary cadmium concentrations were determined repeatedly during the follow-up of a three-year period. The within-person and between-person variability of urinary cadmium concentrations over three years was estimated using multilevel random-effects mixed models. Multivariate regression models were performed to evaluate the associations of cadmium exposure with fasting blood glucose changes and type 2 diabetes mellitus risk. ResultsThe geometric means of creatinine-corrected urinary cadmium concentration at baseline were 1.13 μg/g creatinine, which were close to the levels of follow-up (1.14 μg/g creatinine). The intra-class correlation coefficient of creatinine-corrected urinary cadmium concentrations was 0.71, achieving good reproducibility of cadmium over three years. With adjustment for potential confounders, each one-unit increase in log10-transformed cadmium was associated with a 0.11 (95%CI: 0.03 to 0.19) elevation in fasting blood glucose concentration, and was associated with a 42% (95%CI: 1.16 to 1.73) increase in risk of prevalent type 2 diabetes mellitus. Upward trends of fasting blood glucose changes and type 2 diabetes mellitus incidence were observed with increasing cadmium exposure. Individuals with the highest urinary cadmium exposure had a significant increase in fasting blood glucose change at follow-up [β (95% CI): 0.49 (0.31–0.67)]. Risk of incident type 2 diabetes mellitus were gradually elevated across increasing quartiles of cadmium exposure, though associations did not reach statistical significance (P = 0.15). ConclusionsOur findings suggested that relatively high chronic cadmium exposure for general population adults might contribute to elevated changes of fasting blood glucose resulting in the development of type 2 diabetes mellitus.

Effects of long-term cadmium exposure on trehalose metabolism, growth, and development of Aedes albopictus (Diptera: Culicidae)

Trehalose is the major blood sugar in insects; it not only serves as an energy source but also plays important roles in physiological responses to adverse conditions. However, only a few studies have explored the effects of heavy metal exposure stress on trehalose metabolism in insects. Therefore, in this study, we examined the effects of cadmium stress on changes in trehalose metabolism in Aedes albopictus. Three concentrations of cadmium (0.005, 0.01, and 0.1 mg/L) were selected for evaluation of long-term stress in Ae. albopictus (from eggs to adults); Ae. albopictus in double-distilled water was used as the control group. The trehalose and glucose contents, trehalase activity, and trehalose metabolism-related gene expression were determined. The effects of long-term cadmium exposure on growth, development, and reproduction were also assessed. Trehalose contents were increased, whereas glucose contents and trehalase activity were decreased in Ae. albopictus following long-term exposure to low concentrations of cadmium compared with those in untreated individuals. Moreover, the expression of trehalose-6-phosphate synthase was upregulated, and that of trehalase was downregulated, indicating that Ae. albopictus may enhance trehalose synthesis to resist cadmium stress. Cadmium exposure also caused Ae. albopictus individuals to become smaller with a longer developmental duration, whereas both reproduction and hatching rates of the offspring were decreased compared with those in the control group. Our findings demonstrated that cadmium exposure affected the morphology, physiology, and biochemistry of Ae. albopictus. These findings also confirmed the role of trehalose in the response of Ae. albopictus to cadmium stress, providing insights into the effects of heavy metal stress on trehalose metabolism in an insect model.

Long-term cadmium exposure enhances metallothionein-1 induction after subsequent exposure to high concentrations of cadmium in P1798 mouse lymphosarcoma cells.

Cadmium, a ubiquitous heavy metal, is a toxic industrial and environmental pollutant. The initial biological response to cadmium exposure is induction of metallothioneins (MTs), a family of cysteine-rich, low-molecular-weight proteins that bind primarily zinc, cadmium, or both. This MT induction protects against cadmium toxicity by quenching cadmium. However, the effects of long-term cadmium exposure on MT1 gene expression are largely unknown. To investigate these effects, we used P1798 mouse lymphosarcoma cells, in which the MT1 gene is suppressed. As previously reported, MT1 expression remained unchanged after cadmium treatment. However, MT1 induction was observed in cells treated with 0.1 µM cadmium for 7 days, then exposed to 10 µM cadmium for 3 hr. In cells treated with 0.1 µM cadmium for 7 days, the transfected MT1 promoter reporter gene transcription and the cadmium incorporation in response to 10 µM cadmium induction were similar to those in untreated P1798 cells. Bisulfite genomic sequencing revealed that 7 day treatment with 0.1 µM cadmium slightly decreased CpG methylation in the 5´ flanking region of the MT1 gene. Our results together show that cadmium treatment results in MT1 induction and epigenetic modification of the MT1 gene.

Gender-specific differences of interaction between cadmium exposure and obesity on prediabetes in the NHANES 2007-2012 population.

Data from National Health and Nutrition Examination Survey (NHANES) for the years 2007-2012 were used to evaluate the interactions of cadmium (Cd) exposure with being overweight/obesity on the risk of prediabetes among adults 20 years older. A total of 3552 subjects were included in the analysis. Urinary cadmium levels (UCd) was used as a biomarker for long-term exposure to Cd. Additive interaction was estimated using relative excess risk due to interaction (RERI), attributable proportion due to interaction (AP) and synergy index (S). Following covariates adjustments, we found significant associations of UCd with higher prediabetes prevalence, and this association was more apparent in males (Q4 vs Q1: OR = 1.95, 95%CI: 1.34-2.84); while overweight/obesity was associated with prediabetes both in males and in females. Additionally, there was a significant interaction between Cd exposure and being overweight/obesity on prediabetes risk among males (RERI = 1.18, 95% CI: 0.42-1.93; AP = 0.35, 95% CI: 0.12-0.58; S = 2.00, 95% CI: 0.92-4.34). Our results suggest that being overweight/obesity may substantially amplify the adverse effects of long-term cadmium exposure on prediabetes risk, and this interaction is more severe in male adults. Further studies are needed to confirm these findings.

Effects of long-term cadmium exposure on urinary metabolite profiles in mice.

Cadmium (Cd) is a common environmental pollutant with known toxic effects on the kidney. Urinary metabolomics is a promising approach to study mechanism by which Cd-induced nephrotoxicity. The aim of this study was to elucidate the mechanism of Cd toxicity and to develop specific biomarkers by identifying urinary metabolic changes after a long-term of Cd exposure and with the critical concentration of Cd in the kidney. Urine samples were collected from wild-type 129/Sv mice after 67 weeks of 300 ppm Cd exposure and analyzed by ultra performance liquid chromatography connected with quadrupole time of flight mass spectrometer (UPLC-QTOF-MS) based metabolomics approach. A total of 40 most differentiated metabolites (9 down-regulated and 31 up-regulated) between the control and Cd-exposed group were identified. The majority of the regulated metabolites are amino acids (glutamine, L-aspartic acid, phenylalanine, tryptophan, and D-proline) indicating that amino acid metabolism pathways are affected by long-term exposure of Cd. However, there are also some nucleotides (guanosine, guanosine monophosphate, cyclic AMP, uridine), amino acid derivatives (homoserine, N-acetyl-L-aspartate, N-acetylglutamine, acetyl-phenylalanine, carboxymethyllysine), and peptides. Results of pathway analysis showed that the arginine and proline metabolism, purine metabolism, alanine, aspartate and glutamate metabolism, and aminoacyl-tRNA biosynthesis were affected compared to the control. This study demonstrates that metabolomics is useful to elucidate the metabolic responses and biological effects induced by Cd-exposure.

The effects of long-term cadmium exposure in turkeys: Accumulation and zinc prevention

Experiments with turkeys were conducted to determine the effects of long-term ingestion of Cd (2.0 mg Cd/day/turkey) on its accumulation in the tissues and organs. The cadmium was found especially in the muscles, livers and kidneys. The highest average content of cadmium was found in the kidneys (1.09 mg/kg). The contents of Cd in the kidneys and livers were 19 times and 14 times (respectively) higher compared to the muscles. The administration of Zn (72 mg / day / turkey) along with high doses of Cd, significantly (P < 0.001) reduced the concentrations of Cd in the organs of the experimental animals. The average concentrations of cadmium in the kidneys and livers of turkeys from the CdZn group were 43 % and 48 % (respectively) lower than the average concentrations in the same organs in the turkeys from the group which received only Cd.

Effects of long-term cadmium exposure on growth and metabolomic profile of tomato plants

The response of tomato plants to long-term cadmium exposure was evaluated after a 90-days long culture in hydroponic conditions (0, 20, and 100 μM CdCl 2). Cadmium preferentially accumulated in roots, and to a lower extent in upper parts of plants. Absolute quantification of 28 metabolites was obtained through 1H NMR, HPLC-PDA, and colorimetric methods. The principal component analysis showed a clear separation between control and Cd treated samples. Proline and total ascorbate amounts were reduced in Cd-treated leaves, whereas α-tocopherol, asparagine, and tyrosine accumulation increased, principally in 100 μM Cd treated leaves. Carotenoid and chlorophyll contents decreased only in 100 μM Cd-mature-leaves, which correlate with a reduced expression of genes essential for isoprenoid and carotenoid accumulations. Our results show that tomato plants acclimatize during long-term exposure to 20 μM Cd. On the contrary, 100 μM Cd treatment results in drastic physiological and metabolic perturbations leading to plant growth limitation and fruit set abortion.

The effects of long-term cadmium exposure on the growth and survival of juvenile bull trout ( Salvelinus confluentus)

Bull trout ( Salvelinus confluentus) have been listed recently as threatened in the United States under the federal Endangered Species Act. This species currently resides, or historically resided, in several waterways that either are impacted or are under threat of impact from metals mining activities. We conducted a 55-day sub-chronic (i.e. sublethal) cadmium (Cd) exposure in water at 30 mg l −1 (as CaCO 3) hardness, pH 7.5, and 8 °C. Exposures were conducted using six replicate exposure tanks for each of the six treatments (five Cd concentrations and one control). Measured Cd concentrations were <0.013 (control), 0.052, 0.089, 0.197, 0.383, and 0.786 μg Cd l −1. Exposure to 0.786 μg Cd l −1 caused increased mortality (37%) and reduced growth (28% reduction in weight change) in fish exposed for 55 days. All Cd exposure concentrations caused significant whole body accumulation of Cd compared with controls. Our results indicate that even though fish are significantly accumulating Cd in each non-control treatment, growth reductions in bull trout occurred only at Cd concentrations that also caused significant mortality. The Cd concentration that reduced growth and survival in this long-term exposure (0.786 μg Cd l −1) is greater than the recently-revised US federal aquatic life criteria (ALC) value for the corresponding hardness concentration (ALC=0.62 μg Cd l −1 for acute effects and 0.11 μg Cd l −1 for chronic effects).

Effects of long-term cadmium exposure on the testis of rabbits: Ultrastructural study

Six male rabbits received for 9 months drinking water containing 20 μg/ml of cadmium (Cd). At the end of the treatment, the Cd contents of kidney and testis were 175 ± 34 and 0.8 ± 0.2 μg/g wet weight, respectively. Ultrastructural examination by transmission electron microscopy (EM) showed that, in the Sertoli cells, the size of the lysosomes was increased; spermatogenetic cells, vessels and Leydig cells showed no significant alterations. Observations with both transmission and scanning EM did not evidence changes in the blood-testis barrier, but our results do not exclude that male fertility may be affected by chronic exposure to cadmium.