Environmental cadmium exposure and forearm bone density

Environmental exposure to cadmium may give rise to osteomalacia combined with renal dysfunction, so called 'Itai-Itai disease', which was endemic in the heavily polluted area in Japan. The main focus of this study was to investigate whether environmental exposure to cadmium is associated with low bone mass in a population living near a smelter. A total of 790 persons (302 males and 488 females), who were all over 35 years old and resided in areas near a lead, zinc and cadmium smelter and in a control area in southeast China, 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 present study shows that forearm bone densities were negatively correlated with urinary cadmium excretion (p < 0.001) and forearm bone density decreased linearly with age (p < 0.001) and urinary cadmium (p < 0.01), 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 a 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 gender, leading to osteoporosis and increased risk of fractures, especially in the elderly and in females.     

Environmental cadmium exposure, adverse effects and preventive measures in Japan

In Japan the most heavily cadmium (Cd)-polluted region is the Jinzu river basin, where Itai-itai disease is endemic and the Kakehashi river basin is the second most polluted region.. The village average Cd concentrations in rice were distributed in the range between 0.02 microg/g and 1.06 microg/g in the Jinzu river basin and 0.11 microg g and 0.67 microg g in the Kakehashi river basin. Severe renal damage has occurred widely in the Jinzu river basin. Even after Cd exposure had ceased, renal dysfunction became worse. Dose-response relationships between Cd exposure and health effects were clearly demonstrated in both regions. The allowable limits (according to the present authors' assessment) of Cd concentrations in rice were estimated to be 0.08 microg g to 0.13 microg g and approximately 2 g for total Cd intake. Renal dysfunction caused by exposure to Cd was associated with an increased mortality in both regions. The increased total Cd intake and high concentration of Cd in rice also exerts an adverse influence on life prognosis.     

Low iron diet and parenteral cadmium exposure in pregnant rats: the effects on trace elements and fetal viability

The effects of latent iron deficiency combined with parenteral subchronic or acute cadmium exposure during pregnancy on maternal and fetal tissue distribution of cadmium, iron and zinc, and on fetal viability were evaluated. Timed-pregnant Sprague-Dawley rats were fed on semisynthetic test diets with either high iron (240 mg kg) or low iron (10 mg kg), and concomitantly exposed to 0, 3 or 5 mg cadmium (as anhydrous CdCl₂) per kilogram body weight. Animals were exposed to cadmium from gestation day 1 through 19 by subcutaneously implanted mini pumps (Subchronic exposure) or on gestation day 15 by a single subcutaneous injection (Acute exposure). All rats were killed on gestation day 19. Blood samples, selected organs and fetuses were removed and prepared for element analyses by atomic absorption spectrometry. Low iron diet caused decreases in maternal body weight, maternal and fetal liver weights, placental weights and tissue iron concentrations. By cadmium exposure, both subchronic and acute, tissue cadmium concentrations were increased and the increase was dose-related, maternal liver and kidney zinc concentrations were increased, and fetal zinc concentration was decreased. Cadmium concentration in maternal liver was additionally increased by low iron diet. Acute cadmium exposure caused lower maternal body and organ weights, high fetal mortality, and decreased fetal weights of survivors. In conclusion, parenteral cadmium exposure during pregnancy causes perturbations in essential elements in maternal and fetal compartments. Acute cadmium exposure in the last trimester of gestation poses a risk for fetal viability especially when combined with low iron in maternal diet.     

Genotoxic effects of occupational exposure to lead and cadmium

This study was designed to assess genotoxic damage in somatic cells of workers in a Polish battery plant after high-level occupational exposure to lead (Pb) and cadmium (Cd), by use of the following techniques: the micronucleus (MN) assay, combined with in situ fluorescence hybridization (FISH) with pan-centromeric probes, analysis of sister chromatid exchanges (SCEs), and the comet assay. Blood samples from 44 workers exposed to lead, 22 exposed to cadmium, and 52 unexposed persons were used for SCE and MN analysis with 5'-bromodeoxyuridine (BrdU) or cytokinesis block, respectively. In parallel, the comet assay was performed with blood samples from the same persons for detection of DNA damage, including single-strand breaks (SSB) and alkali-labile sites (ALS). In workers exposed mostly to lead, blood Pb concentrations ranged from 282 to 655 microg/l, while the range in the controls was from 17 to 180 microg/l. Cd concentration in lead-exposed workers fell in the same range as for the controls. In workers exposed mainly to cadmium, blood Cd levels varied from 5.4 to 30.8 microg/l, with respective values for controls within the range of 0.2-5.7 microg/l. Pb concentrations were similar as for the controls. The incidence of MN in peripheral lymphocytes from workers exposed to Pb and Cd was over twice as high as in the controls (P<0.01). Using a combination of conventional scoring of MN and FISH with pan-centromeric probes, we assessed that this increase may have been due to clastogenic as well as aneugenic effects. In Cd- and Pb-exposed workers, the frequency of SCEs as well as the incidence of leukocytes with DNA fragmentation in lymphocytes were slightly, but significantly increased ( P<0.05) as compared with controls. After a 3h incubation of the cells to allow for DNA repair, a clear decrease was found in the level of DNA damage in the controls as well as in the exposed workers. No significant influence of smoking on genotoxic damage could be detected in metal-exposed cohorts. Our findings indicate that lead and cadmium induce clastogenic as well as aneugenic effects in peripheral lymphocytes, indicating a potential health risk for working populations with significant exposures to these heavy metals.     

Low level radiation exposure the radiobiologist's challenge in the next millennium

A formal definition for low level exposure does not exist. This has arbitrarily been defined here as exposures from 0 to 5 cGy. The health implications of exposures within this dose range are highly controversial since the effects are exclusively stochastic. As such, the effects can only be detected in large populations. The Oxford Survey of Childhood Cancers (OSCC) established leukaemia as a predominant effect. After the chernobyl nuclear disaster, studies in European countries have correlated perinatal mortality with radioactive contaminations which could only have raised the radiation burdens by levels which are currently regarded as negligible. The reported risk indices for childhood leukaemia arising from low level exposures are generally comparable to those ascertained for high exposures, thus posing an enigma to radiobiologists. This paper reviews the progress in various areas of radiobiological research and attempts to make a synthesis of the facts with the view to provide an explanation. The purpose is also to stimulate an understanding of multifactorial biological mechanisms. Environmental radiation exposures must be expected to be concomitant with other toxic agents which must be taken into account in risk assessment. The challenge in the future will be to realise this goal.     

Protective effect of zinc against cadmium hepatotoxicity depends on this bioelement intake and level of cadmium exposure: a study in a rat model

It was estimated, in a rat model of moderate and relatively high chronic human exposure to cadmium (Cd), whether enhanced zinc (Zn) consumption may prevent Cd-induced liver injury and if the possible protective effect of this bioelement depends on its intake. For this purpose, the structure and function of the liver of the rats that received Zn (30 and 60 mg/l) or/and Cd (5 and 50 mg/l) for 6 months were evaluated. The treatment with Cd led to, dependent on the exposure level, pathological changes in the liver, including enhanced apoptosis and induction of inflammatory and necrotic processes. Moreover, the serum activities of hepatic marker enzymes (alanine transaminase and aspartate transaminase) and the concentration of proinflammatory cytokine – tumor necrosis factor α were increased. The supplementation with 30 and 60 mg Zn/l (enhancing daily Zn intake by 79% and 151%, respectively) partially or totally prevented from some of the Cd-induced changes in the liver structure and function; however, it provided no protection from necrosis, and the administration of 60 mg Zn/l during the higher Cd exposure even intensified this process. At both levels of Cd treatment, the use of 30 mg Zn/l was more effective in preventing liver injury than that of 60 mg Zn/l. The hepatoprotective impact of Zn may be explained, at least partly, by its antioxidative, antiapoptotic and anti-inflammatory action, ability to stimulate regenerative processes in the liver tissue, and indirect action resulting in a decrease in the liver pool of the non-metallothionein-bound Cd²⁺ ions able to exert toxic action. The results provide strong evidence that enhanced Zn consumption may be beneficial in protection from Cd hepatotoxicity; however, its excessive intake at relatively high exposure to Cd may intensify liver injury.     

The effects of short-term acute cadmium exposure on blue tilapia,Oreochromis aureus

Synopsis Disease-free blue tilapia,Oreochromis aureus, exposed to cadmium (0.5 ppm and 10 ppm) showed very significant and dramatic decrease in food consumptions. Food consumptions returned to near normal 21 days after fish were returned to cadmium-free water. Along with anorexia there were decreases in body weights during the period when fish were exposed to cadmium. Fish in cadmium-free water that were pair-fed to cadmium-exposed fish (0.5 ppm) did not gain weight but there were no decreases in body weights. Cadmium was still in tissues 34 days after the fish were placed in cadmium-free water and the accumulation was highest in the kidney; this was followed by liver, brain, gill filaments and muscles. The accumulations of the heavy metal (in kidneys and gills) were significantly higher in fish exposed to high than low cadmium levels. There were no differences in complement levels (haemolytic acitivity) in cadmium-exposed and cadmium-free fish. However, cadmium-exposed fish did not produce detectable haemagglutinating antibodies against sheep red blood cells while cadmium-free fish responded well to the antigen. The anorexia in cadmium-exposed fish contributed to the depression in antibody production.     

Combination effects of chronic cadmium exposure and gamma-irradiation on the genotoxicity and cytotoxicity of peripheral blood lymphocytes and bone marrow cells in rats

This work investigated the effects of chronic cadmium (Cd) exposure combined with γ-ray irradiation on the cytotoxicity and genotoxicity of peripheral blood cells and bone marrow cells in rats. Results showed that when the rats were exposed to low dose (LD) Cd of 0.1mg CdCl?/(kgd) for 8 and 12 weeks, the Cd concentration in blood reached to 135-140 μg/L and no toxic effects on peripheral blood lymphocytes, white blood cells (WBC) and granulocyte-monocyte (GM) progenitor cells were observed except polychromatic erythrocytes (PCE) of bone marrow. Moreover, this chronic LD Cd exposure significantly decreased irradiation-induced micronucleus (MN) formation and hypoxanthine-guanine phosphoribosyl transferase (hprt) mutation in lymphocytes and PCE, while the combination of LD Cd exposure and irradiation induced the additive metallothionein (MT) protein expression in bone marrow cells. When the rats were exposed to a high dose (HD) Cd of 0.5mg CdCl/?(kgd) for 8 and 12 weeks, the blood Cd level approached to 458-613 μg/L and an inflammatory response was induced, meanwhile, MN formation and hprt mutation were markedly increased, and the ratio of PCE/NCE (normochromatic erythrocyte) was significantly decreased. Furthermore, when the rats were exposed to HD Cd plus 2 Gy irradiation, additive toxic effects on MN formation, hprt mutation, PCE damage and GM progenitor cell proliferation were observed, while this combination treatment resulted in an obvious reduction of MT protein compared to HD Cd group. In conclusion, chronic exposure to LD Cd induced the adaptive response to irradiation in the genotoxicity of peripheral blood lymphocytes and PCE of bone marrow by the up-regulation of Cd-induced MT protein, but the combination of HD Cd exposure and irradiation generated the additive effects on the cytotoxicity and genotoxicity in peripheral blood lymphocytes and bone marrow cells.     

Population level effects of cadmium and the insecticide imidacloprid to the parasitoid, Aphidius ervi after exposure through its host, the pea aphid, Acyrthosiphon pisum (Harris)

The objective of this study was to assess the influence of toxic substances with different modes of action on a two-species system: an aphid-specific parasitoid, Aphidius ervi Haliday, feeding on the pea aphid, Acyrthosiphon pisum (Harris). The instantaneous rate of population increase (r_i) was used as a measure of population level toxic effect in this study. The toxicants evaluated were imidacloprid, a nonpersistent neurotoxic insecticide, and cadmium, a chronic pollutant with a tendency to accumulate. We evaluated the effects of cadmium and imidacloprid on A. pisum and A. ervi because both toxicants can occur together in polluted areas where crops are grown. Cadmium (200 or 400 mg kg⁻¹ dry weight soil) and imidacloprid (4 or 40 g a.i. ha⁻¹) were applied to soil contained in plastic pots in which broad bean plants, Vicia faba L., were grown. Results of this study indicated that cadmium at the concentrations tested, reduced population growth rate of the pea aphid. Imidacloprid also reduced aphid growth rate, but only at the highest concentration tested (40 g a.i. ha⁻¹). Combinations of cadmium and imidacloprid had the greatest impact on aphid growth rate. Imidacloprid alone had no effect on population growth rate of the parasitoid. However, cadmium alone or in combination with imidacloprid had a negative impact on A. ervi by reducing population growth rate 77%. These results indicate that negative impacts on parasitoids may occur in areas where cadmium contamination is present and imidacloprid is used to control aphids.     

Low-salinity stress in the American lobster,Homarus americanus,after chronic sublethal exposure to cadmium: Biochemical effects

Lobsters(Homarus americanus) were exposed to cadmium (6μg l⁻¹, 30 days) in flowing seawater, then held for 7 days in aerated “clean ” seawater at either ambient (27 ‰) or low (17 ‰) salinity. Cadmium exposure alone (ambient salinity) induced a general elevation of enzyme activity (heart, antennal gland, and muscle MDH; heart LDH and GPI), despite the probability of some clearance of cadmium from body tissues during the “clean ” seawater holding period. Low-salinity alone (non-exposed lobsters) caused a decrease of enzyme activity (AAT, LDH, GPI, PK) in most tissues examined, except for tail muscle IDH, the activity of which was increased, and MDH, which was significantly elevated above ambient controls in all tissues except heart. Most low-salinity effects were observed in tail muscle, and most cadmium effects, in heart; low-salinity effects outnumbered cadmium stress by nine to four. In heart and tail muscle of cadmium-exposed lobsters held at low salinity, each of the two stresses apparently operated to nullify the other's effects. The most prominent single biochemical response to these sublethal stresses was the elevation of MDH activity. The ratio MDH: LDH gave the clearest indication of overall relative stress.     

The gender differences in health effects of environmental cadmium exposure and potential mechanisms

On a viewpoint of gender differences in Cd body burden and its health effects, we reviewed the population-based research including our own which conducted in Japan, Thailand, Australia, Poland, Belgium and Sweden to assess health effects of human exposure to environmental cadmium and their potential mechanisms. As a result, six risk factors in Cd health effects in women have been identified; (1) more serious type of renal tubular dysfunction, (2) difference in calcium metabolism and its regulatory hormones, (3) kidney sensitivity; difference in P450 phenotype, (4) pregnancy, (5) body iron store status, and (6) genetic factors. Further studies of Cd toxicity targeted to women would now appear necessary.     

Radiation-induced taste aversion: effects of radiation exposure level and the exposure-taste interval

Radiation-induced taste aversion has been suggested to possibly play a role in the dietary difficulties observed in some radiotherapy patients. In rats, these aversions can still be formed even when the radiation exposure precedes the taste experience by several hours. This study was conducted to examine whether increasing the radiation exposure level could extend the range of the exposure-taste interval that would still support the formation of a taste aversion. Separate groups of rats received either a 100 or 300 R gamma-ray exposure followed 1, 3, 6, or 24 h later by a 10-min saccharin (0.1% w/v) presentation. A control group received a sham exposure followed 1 h later by a 10-min saccharin presentation. Twenty-four hours following the saccharin presentation all rats received a series of twelve 23-h two-bottle preference tests between saccharin and water. The results indicated that the duration of the exposure-taste interval plays an increasingly more important role in determining the initial extent of the aversion as the dose decreases. The course of recovery from taste aversion seems more affected by dose than by the temporal parameters of the conditioning trial.     

Cytochemical study of carp neutrophil granulocytes after acute exposure to cadmium

The aim of this study was determination of metabolical changes in neutrophil granulocytes of common carp (Cyprinus carpio L.) after acute exposure to cadmium chloride. Cytochemical examination of neutrophil granulocytes was performed on 20 control and 20 experimental specimens of 1‐ to 2‐year‐old common carp after 96 h of exposure to cadmium chloride in a concentration of 12.5 mg L^?1. We detected an increase of glycogen and lipid content and a decrease of peroxidase and alkaline phosphatase content in neutrophil granulocytes of the experimental group of carp when compared with the control group.     

The effects of cadmium exposure on the cytology and function of primary cultures from rainbow trout

Cultured epidermal cells from explants of skin of rainbow trout were used to study the cytological and functional changes following sublethal exposure to cadmium stress. The aim was to develop diagnostic markers for ecotoxicology. Cultures were exposed to the pollutant for 48 h. Cell structural and cytological changes were established by light and electron microscopy. Metabolic alterations were detected by immunohistochemistry. The relation between the initiation of cellular alterations and cadmium concentrations was compared in cultures exposed in commercially-available serum-free and serum-containing medium. The expression of stress proteins (metallothionein and heat shock protein) was also studied. Rainbow trout epithelial cells exposed to cadmium showed typical morphological changes indicative of cell death by apoptosis. Sublethal exposure also resulted in cellular metabolic disturbances with increased deposits of glycogen. Increased melanization was also observed. These changes appeared at lower concentrations of cadmium when cells were exposed in serum-free media than in serum-containing media. Cadmium induced the expression of heat shock proteins but not of metallothioneins. The results broadly confirm in vivo findings for cadmium toxicity and suggest that this in vitro technique may have applications in aquatic toxicology. © 1998 John Wiley & Sons, Ltd.     

Early biomarkers of cadmium exposure and nephrotoxicity

As the risks of cadmium (Cd)-induced kidney disease have become increasingly apparent, much attention has been focused on the development and use of sensitive biomarkers of Cd nephrotoxicity. The purpose of this review is to briefly summarize the current state of Cd biomarker research. The review includes overviews of the toxicokinetics of Cd, the mechanisms of Cd-induced proximal tubule injury, and mechanistic summaries of some of the biomarkers (N-acetyl-β-d-glucosamidase; β₂-microglubulin, metallothionein, etc.) that have been most widely used in monitoring of human populations for Cd exposure and nephrotoxicity. In addition, several novel biomarkers (kidney injury molecule-1, α-glutathione-S-transferase and insulin) that offer the potential for improved biomonitoring of Cd-exposed populations are discussed.     

Cigarette smoking,cadmium exposure,and zinc intake on obstructive lung disorder

Background and objective

This study examined whether zinc intake was associated with lower risk of smoking-induced obstructive lung disorder through interplay with cadmium, one of major toxicants in cigarette smoke.

Methods

Data were obtained from a sample of 6,726 subjects aged 40+ from the Third National Health and Nutrition Examination Survey. The forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) were measured using spirometry. Gender-, ethnicity-, and age-specific equations were used to calculate the lower limit of normal (LLN) to define obstructive lung disorder as: observed FEV1/FVC ratio and FEV1 below respective LLN. Zinc intake was assessed by questionnaire. Logistic regression analysis was applied to investigate the associations of interest.

Results

The analyses showed that an increased prevalence of obstructive lung disorder was observed among individuals with low zinc intake regardless of smoking status. The adjusted odds of lung disorder are approximately 1.9 times greater for subjects in the lowest zinc-intake tertile than those in the highest tertile (odds ratio = 1.89, 95% confidence interval = 1.22-2.93). The effect of smoking on lung function decreased considerably after adjusting for urinary cadmium. Protective association between the zinc-to-cadmium ratio (log-transformed) and respiratory risk suggests that zinc may play a role in smoking-associated lung disorder by modifying the influence of cadmium.

Conclusions

While zinc intake is associated with lower risk of obstructive lung disorder, the role of smoking cession and/or prevention are likely to be more important given their far greater effect on respiratory risk. Future research is warranted to explore the mechanisms by which zinc could modify smoking-associated lung disease.     

Early responses to cadmium exposure in barley plants: effects on biometric and physiological parameters

Cadmium represents one of the most toxic pollutants in plant ecosystems: at high concentrations it can cause severe effects, such as plant growth inhibition, decrease in photosynthesis and changes in plant basal metabolism. Changes in pigments’ content, RubisCO large subunit, and D1 protein indicated a severe reduction in photosynthetic efficiency. Furthermore, the decrease of nitrate reductase activity and changes in free amino acids levels show a general stress condition of nitrogen assimilation. Cadmium increased the activities of ROS scavenging enzymes; among these, ascorbate peroxidase rate was the most noticeably increased. It is worth noting that glucose-6-phosphate dehydrogenase (G6PDH; EC 1.1.1.64), showed changes in both activities and occurrence during cadmium stress. Interestingly, our data suggest that G6PDH would modulate redox homeostasis under metal exposure, and possibly satisfy the increased request of reductants to counteract the oxidative burst induced by cadmium. Therefore, the results suggest that APX and G6PDH may play a pivotal role to counteract the oxidative stress induced by cadmium in young barley plants.     

Sex-specific effects of early life cadmium exposure on DNA methylation and implications for birth weight

Dietary cadmium exposure was recently found to alter DNA methylation in adults, but data on effects early in life are lacking. Our objective was to evaluate associations between prenatal cadmium exposure, DNA methylation and birth weight. In total 127 mother-child pairs from rural Bangladesh were studied. For comparison, we included 56 children at 4.5 y. Cadmium concentrations in mothers’ blood (gestational week 14) and children’s urine were measured by ICPMS. Global DNA methylation was analyzed by Infinium HumanMethylation450K BeadChip in cord blood and children’s blood. Maternal cadmium exposure was associated with cord blood DNA methylation (p-value < 10^–16). The association was markedly sex-specific. In boys, 96% of the top 500 CpG sites showed positive correlations (r_S-values > 0.50), whereas most associations in girls were inverse; only 29% were positive (r_S > 0.45). In girls we found overrepresentation of methylation changes in genes associated with organ development, morphology and mineralization of bone, whereas changes in boys were found in cell death-related genes. Several individual CpG sites that were positively associated with cadmium were inversely correlated with birth weight, although none statistically significant after correction for multiple comparisons. The associations were, however, fairly robust in multivariable-adjusted linear regression models. We identified CpG sites that were significantly associated with cadmium exposure in both newborns and 4.5-y-old children. In conclusion, cadmium exposure in early life appears to alter DNA methylation differently in girls and boys. This is consistent with previous findings of sex-specific cadmium toxicity. Cadmium-related changes in methylation were also related to lower birth weight.