Cd-exposed Group Research Articles

Zinc and Copper Levels in Ribs of Cadmium-Exposed Persons with Special Reference to Osteomalacia

Cadmium (Cd), zinc (Zn), copper (Cu), calcium (Ca), phosphorus (P), and magnesium (Mg) were determined in ribs obtained at autopsy from 38 Cd-exposed and 17 nonexposed subjects to determine how levels of these elements in bone are affected by Cd exposure and whether they are associated with the bone lesions due to Cd exposure, osteomalacia, and osteoporosis. Cd in ribs was significantly higher in the Cd-exposed subjects than in nonexposed subjects. Zn tended to be higher, while Cu, Ca, P, and Mg tended to be lower in the ribs of Cd-exposed subjects, though these differences were not statistically significant. Zn, Ca, P, and Mg were highly correlated with each other in both Cd-exposed and nonexposed groups, but the associations of Ca, P, and Mg in the ribs with Zn concentrations differed in subjects and controls. Ca to Zn ratios were low in the Cd-exposed subjects, and the higher the grade of osteomalacia, the lower the Ca/Zn ratio. The decrease in Ca/Zn ratio was significantly correlated with increases in Cd. Cu showed a significant positive correlation with Cd and significant inverse correlation with Ca, P, and Mg in the Cd-exposed group. Cu and its relation to other elements did not show any association with osteomalacia. In conclusion, Ca/Zn ratio in bone was related to Cd exposure and the degree of osteomalacia in the Cd-exposed subjects.

Ontogenic profile of brain lipids following perinatal exposure to cadmium.

Uniparous female rats were exposed to 10 ppm cadmium (as Cd(CH3COO)2) in drinking water, ad libitum, from day 0 of pregnancy; neonates exposed to Cd gestationally and lactationally were separated from their mothers at 21 days of age and were given 10 ppm Cd in drinking water up to 45 days of age. The sequential analysis of brain lipids during development showed a significant reduction in the total lipid levels at 15, 21, 30 and 45 days of age compared to the respective controls. No change in the triglyceride levels was observed in the Cd-exposed group, except for a slight but statistically significant increase (12%, p < 0.05) at day 15 of postnatal life. Metallic exposure also decreased the cholesterol content of brain at different time intervals in comparison to its levels in age-matched control rats. The analysis of sialic acid content of the total gangliosides revealed elevated levels of this group of glycolipids at 21 (25%), 30 (17%) and 45 (23%) days of age compared to their counterpart controls. However, a remarkable reduction in the concentration of brain galactosylceramide (30-43%) and 3'-sulphogalactosylceramide (24-37%) at 21, 30 and 45 days of age was observed following pre- and postnatal exposure of cadmium in comparison to the respective controls. The ontogenic profile of different brain phospholipids in the Cd-exposed group showed an increase in the levels of phosphatidylethanolamine at 21 (31%), 30 (25%) and 45 (19%) days of age; the phosphatidylcholine contents increased at day 21 (14%), followed by a significant decrease at 30 (14%) and 45 (19%) days compared to age-matched controls. Brain phosphatidylinositol, phosphatidylserine and sphingomyelin did not show any alteration at early periods of exposure but decreased significantly following continued exposure by 34%, 45% and 21%, respectively, at 45 days of age. Metal analysis in the brain showed a reduction in zinc and copper levels at 15 and 21 days of age in Cd-exposed animals; however, iron levels remained comparable with control values throughout the experiment. It may be concluded that an early exposure of Cd may produce alteration in the development of different lipids, which may produce CNS dysfunctions with a possibility of being manifested even in later life.

The effect of acute exposure to dietary Cd and Cu on organ toxicant concentrations in rainbow trout, Oncorhynchus mykiss

Trout were fed on a commercial diet containing 10 g of Cd or Cu kg/dry weight of food for 28 days to determine whether fish could ingest and accumulate toxicants from heavily contaminated food. Fish initially ingested either diet, but food regurgitation eventually occurred. Dietary Cd was more toxic than Cu, causing 14 compared to one mortality. Cadmium deposition in internal organs and impaired copper metabolism contributed to mortalities in the Cd-exposed group. Dietary Cd accumulated in the gills, liver, kidney, and muscle. Oral doses of Cu appeared in the gill, liver, and muscle; but not significantly in the kidney. The highest toxicant concentrations were recorded in the gill and liver, while contamination in the muscle was lower than in other tissues examined. Only limited amounts of Cd and Cu were excreted via the body surface mucus. This study suggests that fish will ingest heavily polluted food until toxicity occurs. Wild fish may therefore be at risk from contamination via the diet after pollution incidents.

Assessment of cadmium‐induced osteopenia by measurement of serum bone gla protein, parathyroid hormone, and 1α,25‐dihydroxyvitamin D

To assess the osteopenia induced by environmental cadmium (Cd) exposure by measurement of serum bone Gla protein (BGP), parathyroid hormone (PTH) and 1 alpha,25-dihydroxyvitamin D (1 alpha,25(OH)2D), 29 men and 41 women who lived in a Cd-polluted area and showed renal tubular dysfunction were selected. To evaluate the degree of osteopenia, microdensitometry (MD) was used. Compared with the non-exposed subjects, the levels of serum creatinine and BGP, urinary Cd and beta 2-microglobulin and blood Cd were higher, while the levels of serum inorganic phosphorus and MD indicators were lower in the Cd-exposed group. In simple correlation matrix, BGP showed significant correlations with serum alkaline phosphatase (S-Al-p) and MD indicators in the Cd-exposed men, and also correlations with S-Al-p and 1 alpha-25(OH)2D in the Cd-exposed women. Applying multivariate analysis to the Cd-exposed subjects, BGP, %TRP and base excess were found to show significant associations with the MD indicators in the men. In the women, PTH, age, blood Cd and BGP were associated significantly with the MD indicators. Only serum BGP showed a significant correlation in both sexes of the Cd-exposed subjects, and a sex difference was found in the relationship between bone metabolic markers and osteopenia. These results suggest that serum BGP has a close independent association with the osteopenia induced by Cd exposure and that BGP, which has a different biological function from that of PTH or 1 alpha,25(OH)2D, may be a useful indicator to detect bone damage in Cd-exposed subjects.

Serum vitamin D metabolites in cadmium-exposed persons with renal damage

Serum concentrations of 25-hydroxyvitamin D [25(OH)D], 24,25-dihydroxyvitamin D [24,25(OH)2D], and 1 alpha,25-dihydroxyvitamin D [1 alpha,25(OH)2D] were measured in ten cadmium (Cd)-exposed subjects and five non exposed subjects. The Cd-exposed subjects were divided into two groups according to serum 1 alpha,25(OH)2D levels. No significant differences for 25(OH)D were found between the Cd-exposed group with low or normal serum 1 alpha,25(OH)2D and the non exposed group. The concentrations of 24,25(OH)2D were the lowest in the Cd-exposed group with low serum 1 alpha,25(OH)2D, highest in the non exposed group, and significantly lower in the Cd-exposed group with normal serum 1 alpha,25(OH)2D than in the non exposed group. Renal function was much worse in the Cd-exposed group with low serum 1 alpha,25(OH)2D than in the group with normal serum 1 alpha,25(OH)2D. These findings indicate that Cd initially disturbs hydroxylation from 25(OH)D to 24,25(OH)2D and then disturbs hydroxylation from 25(OH)D to 1 alpha,25(OH)2D. The decrease of serum 24,25(OH)2D and 1 alpha,25(OH)2D in Cd-exposed subjects is not due to a decrease of the serum 25(OH)D level.

Urinary trehalase activity as an indicator of kidney injury due to environmental cadmium exposure.

One hundred and seventy-eight subjects, patients with Itai-itai disease and their family members, aged 12-87 years living in a cadmium (Cd)-polluted area in the Jinzu River basin (Cd-exposed group) and 176 controls (control group) were examined. In the Cd-exposed group urinary trehalase increased with increasing age, urinary beta 2-microglobulin (beta 2-m) and retinol-binding protein. Although urinary cadmium was higher in the Cd-exposed group, no particular correlation was found between urinary trehalase and urinary cadmium. Seventeen men and 11 women showed raised urinary trehalase activities despite normal values of urinary beta 2-m (less than 300 micrograms/g.creatinine), suggesting that urinary trehalase increases earlier than urinary beta 2-m. In 19 patients with Itai-itai disease included in the Cd-exposed group, urinary trehalase decreased with decreasing reciprocal of serum creatinine, suggesting that urinary trehalase decreases in the most advanced cases of chronic cadmium nephropathy due to reduced tubular cell mass.

In vivo measurement of liver and kidney cadmium in workers exposed to this metal: Its significance with respect to cadmium in blood and urine

The cadmium concentration in liver (CdL) and in kidney is measured in vivo by neutron capture γ-ray analysis in 309 male workers occupied in two Belgian zinc-cadmium plants. At the same time, blood cadmium (CdB) and the urinary excretion of β 2-microglobulin, albumin, total protein, calcium, and cadmium (CdU) is also determined. Among the 264 subjects retained for the statistical analysis 236 are still active at the plants (group A) while 28 others are retired Cd workers or workers removed from Cd exposure (group R). Group A comprises 149 subjects with normal renal function who are engaged in jobs not directly related to Cd production (subgroup Ala) and 87 Cd workers daily occupied with Cd production of whom 72 subjects (subgroup Alb) have not and 15 (subgroup A2) have sign(s) of renal dysfunction. Group R is subdivided into subgroups R1 ( n = 10) and R2 ( n = 18), subjects without and with renal dysfunction, respectively. Examination of the cumulative frequency distributions and the correlations between the various biological parameters in the different subgroups leads to the following conclusions: (a) calciuria is not much different among the subgroups, (b) CdB mainly reflects recent exposure to cadmium in the absence of Cd-induced renal damage, (c) CdU follows the body burden of cadmium but increases proportionately much more in workers with renal dysfunction particularly when signs of tubular dysfunction are present, (d) CdL is proportional to duration and intensity of Cd exposure in workers without as well as with renal dysfunction, (e) renal cortical cadmium (CdKc) is higher in subgroup Alb and Rl than in subgroup Ala but does not differ between Cd workers without (subgroup Alb) and with (subgroups A2 and R2) renal dysfunction. The latter finding can be explained by a progressive decrease of CdKc after the onset of the renal damage. This hypothesis is supported by the observations that in Cd workers from subgroup R2. CdKc negatively correlates with years of past exposure to Cd ( r = −0.59), that Cd workers with renal dysfunction (subgroups A2 and R2) excrete significantly more cadmium in urine, and that they show a much lower slope of CdKc versus CdL than those with normal renal function (subgroup Alb). The results of this investigation suggest that there exists a range of critical CdKc levels, i.e., approximately from 160 to 285 ppm. Beyond a CdKc of 285 ppm the probability is very high that all persons will show sign(s) of renal dysfunction. It has been found that kidney dysfunction is likely to develop in workers with CdL between 30 and 60 ppm and that almost all the Cd workers with CdL above 60 ppm evidence renal dysfunction. This study also demonstrates that in the absence of kidney dysfunction. CdU is correlated with the body burden of cadmium ( r = 0.59), but that CdB is not. On the basis of the interrelationships among CdL, CdKc, CdU, and the indicators of renal function, it can be concluded that the probability of developing Cd-induced renal dysfunction in male Cd workers appears to be very low when the critical CdU level of 10 μg/g creatinine is not regularly exceeded. This CdU level corresponds to an average cadmium body burden of 160–170 mg.