| 1. |
- Nordberg, Gunnar, et al.
(författare)
-
Kidney dysfunction and cadmium exposure : Factors influencing dose-response relationships
- 2012
-
Ingår i: Journal of Trace Elements in Medicine and Biology. - : Elsevier BV. - 0946-672X .- 1878-3252. ; 26:2-3, s. 197-200
-
Tidskriftsartikel (refereegranskat)abstract
- Our early toxicological studies showed that metallothionein (MT) is a protein that carries cadmium (Cd) to the kidney, explaining why Cd exposures during long time periods may give rise to kidney dysfunction. This dysfunction is usually considered to be the critical effect, i.e. the adverse effect that occurs at the lowest exposure level. MT also provides intracellular protection against cadmium toxicity. In studies of population groups in cadmium contaminated areas in China, we investigated factors that affected the relationship between internal dose of Cd, as indicated by blood Cd (BCd) or urinary Cd (UCd), and the prevalence of kidney dysfunction. We found dose-response relationships between UCd and the prevalence of increased levels of biomarkers of renal tubular dysfunction (urinary beta-2-microglobulin, B2M, or N-acetyl-beta-D-glucosaminidase - NAG) or urinary albumin (UAlb), a biomarker of glomerular kidney dysfunction. Two years after Cd intake from contaminated rice was diminished, renal tubular dysfunction appeared unchanged or aggravated among those with higher UCd; Another 8 years later, i.e. 10 years after Cd intake was decreased, the prevalence of renal tubular dysfunction was still increased but UAlb had returned to normal. Factors that influenced the dose-response relationships were: (1) time after maximum exposure. (2) Concomitant exposure to other nephrotoxic agents such as inorganic arsenic. (3) Cd induced metallothionein mRNA levels in peripheral blood lymphocytes, used as a biomarker of the ability of each person, to synthesize MT. (4) The occurrence of increased levels in blood plasma of autoantibodies against MT. The two last points further support a role in humans of MT as a protective protein against tissue damage from cadmium and gives support to previous ideas developed partly in experimental systems.
|
|
| 2. |
- Chen, Xiao, et al.
(författare)
-
Changes in bone mineral density 10 years after marked reduction of cadmium exposure in a Chinese population.
- 2009
-
Ingår i: Environmental research. - : Elsevier BV. - 1096-0953 .- 0013-9351. ; 109:7, s. 874-9
-
Tidskriftsartikel (refereegranskat)abstract
- The main focus of this study was to evaluate the long-term effects of Cd on forearm bone mineral density after the cessation of the ingestion of Cd-polluted rice. A total of 458 persons (294 women, 164 men) from three Cd exposure areas (low, moderately, and heavy) participated in this study. Those living in the moderate and heavy exposure areas ceased ingesting Cd-polluted rice (0.51 and 3.7mg/kg, respectively) in 1996 (10 years prior to present analysis). The participants completed a questionnaire and bone mineral density (BMD) was measured by dual energy X-ray absorptiometry (DXA) at the proximal radius and ulna. The changes and change percentage in forearm bone density and the prevalence of osteoporosis between 1998 and 2006 were used as markers of bone recovery. The Cd concentrations in urine (UCd) and blood (BCd) in 1998 were used as Cd exposure markers. The values of the BMD change and change percentage of groups in which UCd was above 5microg/g creatinine (microg/g crea) and BCd was above 10microg/L were significantly higher than those of the low-exposure groups (in women, p<0.001; in men, p>0.05). The BMD change and change percentage correlated positively with the UCd and BCd (in women, p<0.01; in men, p>0.05). Analysis of the Z-score revealed that the prevalence of osteoporosis in 2006 was higher than that in 1998 and increased along with the level of UCd and BCd in both women and men, especially for those subjects with the higher BCd [BCd>5microg/L, OR=3.45 (0.95-13.6); BCd>10microg/L, OR=4.51(1.57-13.54)] and UCd [UCd>10microg/g crea, OR=4.74 (1.82-12.81)] in women. It is concluded that decreasing dietary cadmium exposure at the population level is not associated with bone recovery at the individual level, and the adverse bone effects of Cd exposure persisted after the main source of Cd exposure had been blocked, especially in women.
|
|
| 3. |
- Chen, Xiao, et al.
(författare)
-
The association between dietary cadmium exposure and renal dysfunction - the benchmark dose estimation of reference levels : the ChinaCad study
- 2018
-
Ingår i: Journal of Applied Toxicology. - : John Wiley & Sons. - 0260-437X .- 1099-1263. ; 38:10, s. 1365-1373
-
Tidskriftsartikel (refereegranskat)abstract
- The tolerable dietary intake of cadmium was recommended at provisional tolerable monthly intake of 25gkg(-1) body weight. However, several studies indicated that this tolerable level should be re-evaluated for sufficient health protection. In this study, we show the reference levels of dietary cadmium intake for renal dysfunction by using a benchmark dose (BMD) approach. A total of 790 subjects (302 men and 488 women) living in control and cadmium-polluted areas were included. The dietary cadmium intake was estimated by a food survey. Blood cadmium, urinary cadmium and renal function markers (microalbuminuria, N-acetyl--d-glucosaminidase [NAG] and its isoform B [NAGB], (2)-microglobulin and retinol binding protein) in urine were measured. We calculated the 95% lower confidence bounds of BMD (BMDLs) of cumulative cadmium intake. In control and two polluted areas, the median cumulative cadmium intake was 0.5, 2.1 and 11.1g. The odds ratio of the intermediate (1.0-3.0g), second highest (3.0-11.0g) and the highest cumulative cadmium intake (>11.0g) compared with the lowest cumulative cadmium intake (<1.0g) were 2.8 (95% CI: 1.4-5.8), 8.1 (95% CI: 3.8-17.2) and 11.4 (95% CI: 6.5-26.4) for urinary NAG and 6.6 (95% CI: 3.2-13.8), 14.8 (95% CI: 6.8-32.2) and 22.5 (95% CI: 10.7-47.5) for urinary NAGB. The BMDLs of cumulative cadmium intake were 1.1-1.2g (benchmark response [BMR]=5%) for urinary NAG, and were 0.7-0.9g (BMR=5%) for urinary NAGB, and were 1.3-1.4g (BMR=5%) for urinary (2)-microglobulin. The BMDLs of cumulative cadmium intake in a Chinese population were lower than the critical standard previously reported. Further evaluations are needed for sufficient health protection. Several studies indicated that the tolerable dietary intake of cadmium should be re-evaluated for sufficient health protection. In this study, we show the reference levels of dietary cadmium intake for renal dysfunction by using benchmark dose (BMD) approach. The lowest BMD lower bound confidence limits of cumulative cadmium intake were 0.7-0.9g (benchmark response=5%). The BMD lower bound confidence limits of cumulative cadmium intake were lower than the critical standard previously reported. Further evaluations are needed for sufficient health protection.
|
|
| 4. |
- Liang, Yihuai, et al.
(författare)
-
Increased hepatic and decreased urinary metallothionein in rats after cessation of oral cadmium exposure
- 2010
-
Ingår i: Basic & Clinical Pharmacology & Toxicology. - : John Wiley & Sons. - 1742-7835 .- 1742-7843. ; 106:4, s. 348-355
-
Tidskriftsartikel (refereegranskat)abstract
- We investigated the role of metallothionein (MT) in tissues after cessation of cadmium (Cd) exposure. Wistar rats of both genders were given CdCl(2) in drinking water at daily doses of 0, 2.5, 5.0 or 10.0 mg Cd/kg body-weight for 12 weeks. Half of the animals were then killed; the others were given Cd-free water for the following 16 weeks, i.e. until 28 weeks after start of the experiment (28-week rats). We observed dose-dependent increases in the levels of MT in the tissues of rats 12 weeks after beginning the experiment (12-week rats). After the exposure ceased, levels of MT in the 28-week rats changed in three ways: an increase in the liver, persistence in the kidney cortex and a decrease in the medulla, relative to those levels in their 12-week counterparts. Biomarkers of kidney dysfunction were determined to be urinary MT (UMT) and urinary N-acetyl-beta-d-glucosaminidase (UNAG). After 12 weeks, we observed dose-related statistically significant increases in UMT and UNAG in all of the Cd-exposed groups. A statistically significant decrease for UNAG between the 12- and 28-week rats occurred among males at the lowest Cd dose and for UMT in all of the Cd-exposed groups. The unchanged tissue levels of MT in the kidney cortex suggest that decreased UMT is a sign either of (i) decreased transport of Cd-MT from the liver via blood plasma to the renal tubules or (ii) increased tubular reabsorption and recovery of renal tubular function.
|
|
| 5. |
- Liang, Yihuai, et al.
(författare)
-
Renal function after reduction in cadmium exposure : an eight-year follow-up of residents in cadmium-polluted areas
- 2012
-
Ingår i: Journal of Environmental Health Perspectives. - : National Institute of Environmental Health Sciences. - 0091-6765 .- 1552-9924. ; 120:2, s. 223-228
-
Tidskriftsartikel (refereegranskat)abstract
- Background and objective: Long-term exposure to cadmium (Cd) causes renal dysfunction, but its change with exposure is unknown. We aimed at assessing the evolution of Cd-induced renal effects after a reduction in dietary exposure to Cd in rice.Methods: 412 residents in previously Cd-polluted and non-polluted areas were examined twice: in 1998 and 2006. Changes in blood Cd, urinary Cd, and kidney function (N-acetyl-β-D-glucosaminidase = NAG, β2-microglobulin, and albumin in urine) were measured. Results: In the most polluted area, mean blood Cd was 8.9 μg/L in 1998 and 3.3 μg/L in 2006, and urinary Cd was 11.6 and 9.0 μg/g creatinine in 1998 and 2006, respectively. Urinary albumin in 1998 increased with urinary Cd but no such exposure-response appeared for 2006 albumin versus urinary Cd 1998, indicating recovery. Other biomarkers of kidney function were also elevated in 1998. Partial recovery was observed for NAG, among women, and suggested for β2-microglobulin, among young individuals. The probability of having a β2-microglobulin above the 95th percentile in 2006 was high in those with an elevated β2-microglobulin in 1998 (odds ratio: 24.8, 95% CI: 11.2-55.3), whereas corresponding estimates for albumin and NAG were 3.0 (1.2-7.5) and 2.6 (1.6-4.4), respectively.Conclusions: Results suggest that a Cd-mediated increase in urinary albumin excretion is reversible upon substantial reduction of exposure. For the markers of tubular effects, a tendency towards improvement, but not complete recovery, was observed. Data from repeated observations suggests that β2-microglobulin may be more informative than NAG as an indicator for the individual's future tubular function.
|
|
| 6. |
|
|
| 7. |
- Tian, Liting, et al.
(författare)
-
Lead concentration in plasma as a biomarker of exposure and risk, and modification of toxicity by delta-aminolevulinic acid dehydratase gene polymorphism
- 2013
-
Ingår i: Toxicology Letters. - : Elsevier BV. - 1879-3169 .- 0378-4274. ; 221:2, s. 102-109
-
Tidskriftsartikel (refereegranskat)abstract
- Blood lead concentration (B-Pb), the main biomarker of lead exposure and risk, is curvi-linearily related to exposure. We assessed plasma lead (P-Pb) as a marker for both lead exposure and toxic effects. We examined claims that delta-aminolevulinic acid dehydratase genotype (ALAD) can modify lead toxicity. In 290 lead-exposed and 91 unexposed Chinese workers, we determined P-Pb, B-Pb, urinary lead (U-Pb), AMD polymorphism (rs1800435, ALAD112; TaqMan assay), and also toxic effects on heme synthesis (blood zinc protoporphyrin and hemoglobin, urinary delta-aminolevulic acid), on the kidneys (urinary albumin, beta(2)microglobulin and N-acetyl-beta-D-glucosaminidase) and on the peripheral nervous system (sensory and motor conduction velocities). In exposed workers, median P-Pb was 4.10 (range 0.35-27) mu g/L, B-Pb 401 (110-950) mu g/L, and U-Pb 188 (22-590) mu g/g creatinine. P-Pb had a higher ratio between exposed and unexposed workers (median 39, range 18-110) than B-Pb (19, 15-36; p<0.001) and U-Pb (28, 15-36; p<0.001). All three biomarkers were associated with all toxic effects (P-Pb: r(s)= -0.10 to 0.79; B-Pb: r(s) = -0.08 to 0.75; all p <0.05). In the exposed workers, B-Pb and U-Pb were significantly higher (p = 0.04) in AIAD2 carriers (7% in the exposed population) than in ALAD1 homozygotes. P-Pb values were similar; ALAD1 homozygotes suffered higher kidney toxicity at the same P-Pb. Conclusions: (i) P-Pb has advantages over B-Pb as a biomarker of high Pb exposure, but it was not significantly better as an index of risk of toxicity. (ii) The ALAD genotype modifies toxicokinetics and toxicodynamics. (C) 2013 Elsevier Ireland Ltd. All rights reserved.
|
|
| 8. |
- Wu, Xunwei, et al.
(författare)
-
Renal effects evolution in a Chinese population after reduction of cadmium exposure in rice.
- 2008
-
Ingår i: Environmental research. - : Elsevier BV. - 1096-0953 .- 0013-9351. ; 108:2, s. 233-8
-
Tidskriftsartikel (refereegranskat)abstract
- Cadmium is a well-known nephrotoxic agent with extremely long biological half-time of 10-30 years in human. To investigate the evolution of cadmium-induced renal effects in the population, a number of 148 residents who lived in cadmium-polluted area were followed-up for 3 years after the reduction of cadmium exposure in rice. Urinary cadmium (UCd), beta(2)-microglobulin (B2M) and albumin (ALB) were analyzed in 1995 and 1998, respectively. The results demonstrated that the changes of renal effects of residents depended on the levels of UCd before inflow of cadmium to human body declined. In cases where UCd were less than 10 microg/g creatinine in 1995, evidence was found indicating significant decreases in proteinuria (i.e., B2M and ALB) 3 years later, whereas, in cases where the excretion of UCd exceeded 10 microg/g creatinine in 1995, progression was observed. The study of dose-response relationships between UCd and B2M or ALB also showed that the cadmium-induced renal dysfunction might be reversible if UCd concentration was low-level before exposure decreasing, otherwise it might be irreversible or aggravated.
|
|
| 9. |
- Zheng, Guang, et al.
(författare)
-
δ-Aminolevulinic acid dehydratase genotype predicts toxic effects of lead on workers' peripheral nervous system
- 2011
-
Ingår i: Neurotoxicology. - : Elsevier BV. - 0161-813X .- 1872-9711. ; 32:4, s. 374-382
-
Tidskriftsartikel (refereegranskat)abstract
- There is a wide variation in sensitivity to lead (Pb) exposure, which may be due to genetic susceptibility towards Pb. We investigated whether a polymorphism (rs1800435) in the δ-aminolevulinic acid dehydratase (ALAD) gene affected the toxicokinetics and toxicodynamics of Pb. Among 461 Chinese Pb-exposed storage battery and 175 unexposed workers, allele frequencies for the ALAD1 and ALAD2 alleles were 0.968 and 0.032, respectively. The Pb-exposed workers had a higher fraction of the ALAD1-2/2-2 genotype than unexposed workers (7.8% vs. 2.3%, p=0.01). The Pb levels in blood (B-Pb) and urine (U-Pb) were higher in Pb-exposed workers carrying the ALAD2 allele compared to homozygotes for ALAD1 (median B-Pb: 606 vs. 499 μg/L; U-Pb: 233 vs. 164 μg/g creatinine), while there was no statistically significant difference in the unexposed controls (median: 24 vs. 37 μg/L, and 3.9 vs. 6.4μg/g creatinine, respectively). High B-Pb and U-Pb were associated with statistically significantly lower sensory and motor conduction velocities in the median, ulnar and peroneal nerves. At the same B-Pb and U-Pb, ALAD1 homozygotes had lower conduction velocities than the ALAD2 carriers. There were similar trends for toxic effects on haem synthesis (zinc protoporphyrin and haemoglobin in blood) and renal function (albumin and N-acetyl-d-β-acetylglucosaminidase in urine), but without statistical significance. There was no difference in Pb toxicokinetics and toxicodynamics associated with VDR BsmI polymorphism. Our results show that the ALAD genotype modifies the relationship between Pb and its toxic effects on the peripheral nervous system. This must be considered in the assessment of risks at Pb exposure.
|
|
