Taiyi Jin

Influence of Environmental Cadmium Exposure on Forearm Bone Density

Cadmium may have both direct and indirect effects on bone turnover. It is nephrotoxic and can interfere with vitamin D metabolism. Such perturbation may result in osteoporosis and osteomalacia. In this study, a total of 790 persons (302 males and 488 females) participated; they were all over 35 years old and resided in an area near a cadmium smelter in southeast China. All participants completed a questionnaire, and bone mineral density was measured by SPA‐4 single‐photon absorptiometry at the radius and ulna. Cadmium content of urine was determined by graphite‐furnace atomic absorption spectrophotometry as a measure of dose. The decline in bone mineral density with age in a heavily polluted area was greater than that in a control area for subjects over 60 years of age of both sexes (p < 0.05). In single regression, forearm bone densities were negatively correlated with urinary cadmium excretion in both males and females (p < 0.001), whereas stepwise regression showed that forearm bone density decreased linearly with age (p < 0.001) and urinary cadmium (p < 0.01) in both sexes, suggesting a dose‐effect relationship between cadmium dose and bone mineral density. Based on the World Health Organization criteria, (bone mineral density < −2.5 SDs below the normal young adult), the prevalence of osteoporosis in women increased from 34.0% in the control area to 51.9% in the heavily polluted area (p < 0.01) among subjects over 50 years old, and the odds ratio value was 2.09 (95% CI: 1.08–4.03) for the highly polluted area compared with the control area. A striking observation in the study was the marked increase of the prevalence of fracture in the cadmium‐polluted area in both sexes. It was concluded that environmental exposure to cadmium is associated with an increased loss of bone mineral density in both males and females, leading to osteoporosis and increased risk of fractures, especially in the elderly and in females.

Low Bone Density and Renal Dysfunction Following Environmental Cadmium Exposure in China

Abstract This paper presents the main findings of a study on health effects of environmental cadmium pollution in China, performed in 1998, i.e. approximately 25 years after the first warnings of such effects were published in Ambio. Forearm bone mineral density (BMD) and renal dysfunction were assessed in population groups exposed to cadmium via rice. Decreased BMD was found in postmenopausal women with elevated urinary cadmium (CdU) or cadmium in blood (CdB) and among men with elevated CdB. Also, clear and statistically significant dose-effect and dose-response relationships were found between CdB or CdU and renal dysfunction (increased excretion of retinol-binding protein). This is the first report of bone effects among Cd-exposed population groups in Asia outside Japan. The report is also of interest since it demonstrates that bone effects, a comparatively severe adverse health effect of Cd, in combination with renal dysfunction, still occurs in environmentally exposed population groups in Asia. Recent reports on bone effects in Cd-exposed population groups in Europe are discussed.

Cadmium-induced apoptosis and changes in expression of p53, c-jun and MT-I genes in testes and ventral prostate of rats

Apoptosis and a change in the expression of p53, c-jun and MT-I genes occurred in rats exposed to cadmium in a way known to cause carcinogenesis in testes and ventral prostate. In situ end labelling (ISEL), DNA electrophoresis, and RT-PCR methods were used in present study. Adult male Wistar rats were given a single (s.c.) injection of 0, 5, 10, or 20 micromol/kg CdCl2. Then 12, 48 or 96 h after administration of cadmium, animals were sacrificed. It was observed that cadmium markedly induced apoptosis in the testes at the dose of 5 micromol/kg while 10 and 20 micromol/kg cadmium caused more necrosis than apoptosis. Apoptosis in the ventral prostate was markedly induced by all the doses of cadmium and there was an obvious time- and dose-dependent relationship between apoptotic index (AI) and cadmium treatment. Far fewer apoptotic cells appeared in liver, compared to the testes and ventral prostate. p53 mRNA expression was clearly enhanced in the ventral prostate but clearly suppressed in the testes by cadmium exposure, and the time- and dose-effect was very clear. The expression level of p53 in the liver was not affected by cadmium treatment. Cadmium-induced overexpression of c-jun gene appeared at 12 h in the liver, but not until 96 h in the testes and ventral prostate. Although the MT-I gene was found to be expressed in all tissues, marked induction by cadmium of the expression of MT-I gene was only observed in the liver. These results indicate: (1) that apoptosis is an early mechanism of acute tissue damage by cadmium in the testes and ventral prostate; (2) that p53 and c-jun genes may be involved in cadmium-induced cytotoxicity (apoptosis) and related carcinogenicity in male reproductive tissues; and (3) that the enhanced expression of MT-I in the liver could protect this organ from cadmium-induced cytotoxicity (apoptosis) and carcinogenicity.

Biological monitoring of cadmium exposure and renal effects in a population group residing in a polluted area in China.

In an area of China, not previously studied in detail concerning cadmium pollution and possible adverse effects on the kidney of exposed populations, concentrations of cadmium in urine as an indicator of renal accumulation of cadmium was studied and related to indicators of renal dysfunction in order to examine if a relationship could be documented. Cadmium concentrations in urine were analysed by graphite furnace atomic absorption spectrometry and urinary beta-2 microglobulin (UBM) and albumin (UALB) were measured as indicators of renal dysfunction, Rice samples and urine samples were obtained from three areas in Zhejiang province, China, representing a highly exposed area, a medium exposed area and a control area, respectively. Cadmium concentrations in rice were 3.70, 0.51 and 0.072 mg/kg for the heavily, medium polluted areas and the control area, respectively. Cadmium concentrations in urine (geometric means) were 10.7, 1.62 and 0.40 micrograms/l in the high, medium and control areas respectively. There was a clear increase in UBM and UALB in the heavily exposed group in comparison to the control group and a slight increase in the medium exposed group. There was a statistically significant dose-response relationship between cadmium in urine and beta 2-microglobulin excretion in urine, which is similar to what has previously been reported in other countries. The findings constitute the first report concerning a dose-response relationship in this population group in Zhejiang province in China.

Urinary calcium as a biomarker of renal dysfunction in a general population exposed to cadmium.

Urinary &bgr;2-microglobulin and N-acetyl-&bgr;-d-glucosaminidase have been recommended as sensitive indicators of renal dysfunction induced by cadmium. However, an increase in urinary calcium in early renal damage induced by cadmium has been reported both in humans and in animal experiments. To investigate the feasibility of using urinary calcium as a biomarker of renal dysfunction induced by cadmium, two areas were selected in this study, namely, a polluted area with a 3.71 mg/kg cadmium concentration in rice and a control area with a 0.07 mg/kg cadmium concentration. The total number of participants was 499, made up of 252 in the control group and 247 from the cadmium-polluted area. Urinary cadmium, urinary calcium, and zinc concentrations were measured by atomic absorption spectrometry, and &bgr;2-microglobulin and N-acetyl-&bgr;-d-glucosaminidase in urine were analyzed. The levels of urinary cadmium and urinary calcium in persons from the exposed area were significantly higher (P < 0.05) than those in the control area for both men and women, but there was no significant difference regarding urinary zinc between the two areas. A significant dose-response relationship between the prevalence of hypercalciuria and the excretion of urinary cadmium was observed, and a significantly increased prevalence of calciuria was found when excretion of urinary cadmium exceeded 2 &mgr;g/g creatinine. The findings were similar to those for excess urinary secretion of &bgr;2-microglobulin and N-acetyl-&bgr;-d-glucosaminidase. Because cadmium can affect Ca2+ uptake by tubular cells, with decreased renal Ca2+ reabsorption, calciuria may reflect tubular cell damage caused by cadmium. It was concluded that cadmium exposure can result in increased excretion of urinary calcium in a general population and that there is a significant dose-response relationship. Urinary calcium can therefore be used as a biomarker of renal dysfunction induced by cadmium.

Renal effects evolution in a Chinese population after reduction of cadmium exposure in rice

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.

Renal function after reduction in cadmium exposure: an 8-year follow-up of residents in cadmium-polluted areas.

Background and objective: Long-term exposure to cadmium (Cd) causes renal dysfunction, but the change in renal function with exposure is unknown. We assessed the evolution of Cd-induced renal effects after a reduction in dietary exposure to Cd in rice. Methods: Four hundred twelve residents in previously Cd-polluted and nonpolluted areas were examined twice, in 1998 and in 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 and 3.3 μg/L in 1998 and in 2006, respectively, and urinary Cd was 11.6 and 9.0 μg/g creatinine. Urinary albumin in 1998 increased with urinary Cd, but no such exposure–response relation 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 was suggested for β2-microglobulin among young individuals. The probability of having β2-microglobulin levels above the 95th percentile in 2006 was high in those with elevated β2-microglobulin in 1998 [odds ratio (OR) = 24.8; 95% confidence interval (CI): 11.2, 55.3] compared with albumin (OR = 3.0; 95% CI: 1.2, 7.5) and NAG (OR = 2.6; 95% CI: 1.6, 4.4). Conclusions: Results suggest that a Cd-mediated increase in urinary albumin excretion is reversible upon substantial reduction of exposure. For markers of tubular effects, we observed a tendency toward improvement but not complete recovery. Data from repeated observations suggest that β2-microglobulin may be more informative than NAG as an indicator for an individual’s future tubular function.

Metallothionein gene expression in peripheral lymphocytes from cadmium-exposed workers

Abstract Metallothionein (MT) plays an important role in the detoxification of cadmium.To investigate the usefulness of MT gene expression in peripheral blood lymphocytes (PBLs) as a biomarker of cadmium exposure and susceptibility, reverse transcriptase–polymerase chain reaction was used to measure the MT gene expression in PBLs from cadmium-exposed workers. Both basal and induced MT expressions were found to increase with increased blood cadmium (BCd) and urinary cadmium (UCd) levels. Both basal and induced MT expression levels were significantly correlated with the logarithm of BCd and the logarithm of UCd levels. The dose-response relationship between internal dose of cadmium and MT expression suggested the validity of MT expression in PBLs as a biomarker of cadmium exposure. In vitro induced MT expression level in PBLs was found to be inversely related to the level of renal dysfunction indicator, urinary N-acetyl-β-d-glucosaminidase (UNAG). The latter finding indicates that MT expression in PBLs may be a useful biomarker of susceptibility to renal toxicity of cadmium. (Presented in part at the International Symposium on Metal-Binding Proteins in Biology, Banff, Canada, 1998.)

Effects of cadmium on osteoblasts and osteoclasts in vitro

Cadmium (Cd) may have direct effects on bone metabolism and the mechanism is not fully understood. To investigate the effects of Cd on bone metabolism, effects of Cd on osteoblasts and osteoclasts in vitro were observed at cellular and molecular levels. Osteoblasts were cultured by sequential enzyme digestion from Sprague-Dawley rats calvarial bone and osteoclasts were isolated from long bones of new-born male and female Sprague-Dawley rats, and then cells were exposed to different concentrations of Cd (0-2.0 μ mol/L for osteoblasts; 0.03 μmol/L for osteoclasts). As for osteoblasts, cell viability, alkaline phosphatase (ALP) activity, and mineralization were determined. Osteoprotegerin (OPG) and receptor activator of NF-kB ligand (RANKL) were studied via reverse transcription-polymerase chain reaction (RT-PCR). For osteoclasts, after exposure to Cd (0.03 μmol/L) for 72 h and 120 h, number of osteoclasts and pits formation was observed. Cd inhibited the viability, ALP activity, mineralization and up-regulated RANKL mRNA expression in osteoblasts. But Cd had no obvious effect on OPG mRNA expression. For osteoclasts, cadmium (0.03 μmol/L) could increase the numbers of osteoclasts (p<0.05) and enhance pits formation (p<0.05). These results suggested that Cd could inhibit bone formation at high concentrations and enhance bone resorption at low level. OPG/RANKL may constitute an important pathway of Cd effects on bone.

Effects on the prostate of environmental cadmium exposure – A cross-sectional population study in China

To explore possible effects of environmental cadmium exposure on prostate in humans, and the possible relationship of serum sex hormones to occurrence of clinic signs of tissue changes in the prostate, a case-control study was undertaken in the southeast part of China in 1998. A total of 297 male volunteers from a control area and two cadmium-polluted areas were included as subjects in this study. All the subjects were required to answer a questionnaire and to undergo a complete physical examination including digital-rectal examination (DRE). Blood and urine samples were collected. Serum total prostate specific antigen (PSA), total serum testosterone (T), follicle stimulating hormone (FSH) and luteinizing hormone (LH) were measured by radioimmunoassay and enzymeimmunoassay method, respectively. The data of urinary cadmium (U-Cd) and blood cadmium (B-Cd) were obtained by atomic absorption spectrometry (AAS) as an indicator of cadmium body burden. Statistical analysis was applied to investigate a possible relation between cadmium exposure and prostate pathological changes. The results show that there is a clear dose-response relationship between cadmium exposure and the prevalence of cases with abnormal PSA. The blood cadmium content in cases with positive DRE was significantly higher than that of subjects with negative DRE (P<0.05). Significant differences in the level of FSH between cases with positive DRE and the normal subjects were also noted (P<0.05). These results indicate that chronic environmental cadmium exposure is associated with injuries to human prostate. A possible relationship to changes in circulating sex hormones needs further investigation.