Enhanced Zinc Intake Protects against Oxidative Stress and Its Consequences in the Brain: A Study in an In Vivo Rat Model of Cadmium Exposure.

We examined, in a rat model of moderate environmental human exposure to cadmium (Cd), whether the enhanced intake of zinc (Zn) may protect against Cd-caused destroying the oxidative/antioxidative balance and its consequences in the brain. The intoxication with Cd (5 mg/L, 6 months) weakened the enzymatic (superoxide dismutase, glutathione peroxidase, catalase) and non-enzymatic (total thiol groups, reduced glutathione) antioxidative barrier decreasing the total antioxidative status and increased the concentrations of pro-oxidants (hydrogen peroxide, myeloperoxidase) in this organ and its total oxidative status. These resulted in the development of oxidative stress and oxidative modifications of lipids and proteins. The co-administration of Zn (30 and 60 mg/L enhancing this element intake by 79% and 151%, respectively) importantly protected against Cd accumulation in the brain tissue and this xenobiotic-induced development of oxidative stress and oxidative damage to lipids and proteins. Moreover, this bioelement also prevented Cd-mediated oxidative stress evaluated in the serum. The favorable effect of Zn was caused by its independent action and interaction with Cd. Concluding, the enhancement of Zn intake under oral exposure to Cd may prevent the oxidative/antioxidative imbalance and oxidative stress in the brain and thus protect against injury of cellular macromolecules in the nervous system.

High dose of standardised extract of Costus afer leaves potentiates cadmium reproductive toxicity in Wistar rats.

Protective effects of standardised extract of Costus afer leaves (CAME), an extract with good antioxidants on cadmium-induced reproductive toxicity in male rats, were investigated in this study. Forty-two adult male Wistar rats were randomly divided into six groups and were treated every day regularly for 4 weeks. G1 (control) rats received 1 ml of vehicle treatment. G2 rats were intoxicated with 2.5 mg kg-1  day-1 s.c cadmium chloride for 1 week. G3 and G4 rats were intoxicated with cadmium as in G2 rats and were treated orally with 100 and 200 mg/kg bwt/day of CAME, respectively, for 4 weeks. Group G5 and G6 rats were orally treated with 100 and 200 mg kg-1  day-1 bwt of CAME, respectively, for 4 weeks. Significant changes (p < 0.05) in andrological parameters (sperm count, sperm morphology, serum testosterone and nitric oxide concentration) and testicular antioxidant parameters (reduced glutathione, lipid peroxidation and activities of catalase, glutathione S-transferase and glutathione peroxidase) caused by Cd toxicity were improved in cadmium-intoxicated rats treated with 100 mg/kg body weight of CAME. Administration of 200 mg/kg body weight of CAME to cadmium-intoxicated rats potentiated reproductive toxic effects of cadmium. In conclusion, lower dose of CAME is preferred over high dose in treatment of cadmium-induced reproductive toxicity in rats.

Hospital-based screening to detect patients with cadmium nephropathy in cadmium-polluted areas in Japan.

BACKGROUND: In health examinations for local inhabitants in cadmium-polluted areas, only healthy people are investigated, suggesting that patients with severe cadmium nephropathy or itai-itai disease may be overlooked. Therefore, we performed hospital-based screening to detect patients with cadmium nephropathy in two core medical institutes in cadmium-polluted areas in Akita prefecture, Japan. METHODS: Subjects for this screening were selected from patients aged 60 years or older with elevated serum creatinine levels and no definite renal diseases. We enrolled 35 subjects from a hospital in Odate city and 22 from a clinic in Kosaka town. Urinary ß2-microglobulin and blood and urinary cadmium levels were measured. RESULTS: The criteria for renal tubular dysfunction and the over-accumulation of cadmium were set as a urinary ß2-microglobulin level higher than 10,000 µg/g cr. and a blood cadmium level higher than 6 µg/L or urinary cadmium level higher than 10 µg/g cr., respectively. Subjects who fulfilled both criteria were diagnosed with cadmium nephropathy. Six out of 57 patients (10.5% of all subjects) had cadmium nephropathy. CONCLUSIONS: This hospital-based screening is a very effective strategy for detecting patients with cadmium nephropathy in cadmium-polluted areas, playing a complementary role in health examinations for local inhabitants. REGISTRATION NUMBER: No. 6, date of registration: 6 June, 2010 (Akita Rosai Hospital), and No. 1117, date of registration: 26 December, 2013 (Akita University).

The references level of cadmium intake for renal dysfunction in a Chinese population.

Recent several studies indicated that a more restrictive dietary intake guideline for cadmium should be made for sufficient health protection. In the present study, we showed the references level of food cadmium intake (FCd) and total cadmium intake (TCd) for renal dysfunction by using benchmark dose (BMD) approach. 342 subjects living in a control and a cadmium polluted area were included in this study. The FCd, TCd and cadmium in urine (UCd) and blood (BCd) were calculated or determined. Urinary ß2Microglobulin (UBMG) was determined as indicator of renal function. The median FCd, TCd, UCd and BCd were 1.4 g, 1.4 g, 3.1 µg/g creatinine(cr) and 1.3 µg/L in control and 3.3 g, 3.6 g, 13.5 µg/g cr and 12.1 µg/L in polluted area. The 95% lower confidence bounds of BMD (BMDLs) of FCd for renal dysfunction were 1.36-1.55 g (BMR = 10%) and 0.88-1.11 g (BMR = 5%). The BMDLs of TCd were 1.29-1.46 g (BMR = 10%) and 0.73-0.95 g (BMR = 5%). FCd and TCd are valuable markers for the predication of renal dysfunction induced by cadmium. The BMDLs of FCd were close to previous report in Japan and the BMDLs of TCd were lower than the critical standard previously reported, in particular at BMR of 5% which can be interpreted as representing the influence of smoking.

Causes of death in patients with Itai-itai disease suffering from severe chronic cadmium poisoning: a nested case-control analysis of a follow-up study in Japan.

OBJECTIVE: To clarify the causes of deaths among patients with Itai-itai disease and severe cadmium (Cd) poisoning. DESIGN: Nested case-control analysis of a population-based cohort study. SETTING: Database of patients with Itai-itai disease and residents of Cd-polluted areas, maintained by the Ministry of Environment, Japan. PARTICIPANTS: Subjects included 142 women with Itai-itai disease, 111 women with Cd-induced renal tubular dysfunction and 253 controls matched for sex, age and occupation. All subjects participated in a health impact survey between 1979 and 1984 and were followed until 30 November 2005. MAIN OUTCOMES AND MEASURES: Adjusted HRs with 95% CIs for cause of death in women with Itai-itai disease and screened female cases with tubular dysfunction were compared with matched pair controls, using Cox's proportional hazard model. Vital statistics data were used to determine cause of death. Direct causes of death from autopsy records were used in 29 patients who died from Cd poisoning. RESULTS: The most common cause of death among patients with Itai-itai disease was pneumonia, with a significantly increased adjusted HR of 4.54 (95% CI 2.65 to 7.76). Renal diseases were the most common cause of death in renal tubular dysfunction cases, with an increased HR of 12.0 (95% CI 3.92 to 36.8). The adjusted HR for renal diseases was also significantly increased in patients with Itai-itai disease (19.49 (95% CI 6.43 to 59.09)), with a greater impact on mortality of patients with Itai-itai disease than screened cases. The HR for gastrointestinal (GI) diseases was significantly increased (13.79 (95% CI 3.87 to 49.10)) in patients, especially in the first 10 years (37.1 (4.81 to 286.0)). CONCLUSIONS: Among patients with Itai-itai disease, pneumonia and GI diseases contributed to increased mortality risk. Renal disease is also a significant mortality risk in patients with Itai-itai disease and women with renal tubular dysfunction.

Chronic kidney disease of uncertain aetiology: adding vital piece of information to the national project team report of Sri Lanka.

In a recent study published by the National Project Team on chronic kidney diseases of unknown origin in Sri Lanka, identified cadmium as a major risk factor but strong conclusions were not made as the identified environmental toxins were within the permissible levels.Sri Lankan food consumption pattern is different so that approach of total exposure of cadmium by food and water been calculated. Such calculation point out that total exposure of cadmium exceed the provisional tolerable weekly intake determined by international agencies.

[Selected work-related nephropathies]. / Wybrane choroby nerek zwiazane z praca.

Infections, high temperature and many of the toxic substances can cause kidney damage. Acute kidney injury is a well known complication of some work-related diseases, e.g., lead intoxication. Chronic kidney disease can also be caused by some occupational factors. Three work-related nephropathies, in which causal connection with work has been proved, are discussed in this article. There are different risk factors of nephrolithiasis, lead nephropathy and silica nephropathy, but each of them can cause chronic kidney disease. Prevention of these nephropaties seems to be relatively simple. The principles of protection from the toxic effects of heavy metals and silica dust are very specific. The most important prevention of kidney stones is correct fluid intake. In addition to providing adequate quantities of drinking water, it is also important to educate exposed workers and assure enough rest breaks at work.

Cadmium status among pediatric cancer patients in Egypt.

Cadmium (Cd) is a toxic, nonessential, and bio-accumulating heavy metal widely used in industry. Several studies have suggested a positive association between Cd exposure and risks of several cancers. However, data from general population, especially children are sparse.In the current cross-sectional case-control study, we aimed to assess the association between Cd exposure, as expressed by Cd body status (blood, urine, scalp hair, and nails) and cancer among Egyptian children. Three hundred and fifty pediatric cancer cases aged 3 to 14-years old were enrolled in our study. Their body Cd levels were evaluated using Atomic Absorption Spectrophometer and were compared with Cd levels of 350 healthy children.Significantly higher Cd levels (blood, urine, scalp hair, and nails) were documented in cancer cases when compared with control (P < 0.001). Such difference was still detected when comparing each malignant type separately, with controls. Tobacco smoke exposure, rural residence, and low socioeconomic status were reported more frequently among cases than comparisons.Positive association between Cd exposure and pediatric malignancy may be present.

Environmentally Realistic Doses of Cadmium as a Possible Etiologic Agent for Idiopathic Pathologies.

Cadmium is a heavy metal of increasing environmental concern that has long been associated to several human pathological processes. Recent population surveys have correlated cadmium non-occupational exposure to widespread idiopathic pathologies. Food and tobacco are reported to be the main exposure sources of cadmium to the general population, as phosphate fertilizers are rich in such a metal, thus contaminating the crops. Although its mechanisms of toxicity are not a consensus in the literature, it is well established that reactive oxygen species play a key role in this process, leading to the oxidation of several biological molecules. We have therefore assessed whether three environmentally realistic doses of cadmium alter the oxidative status of Wistar rat testis and eventually result in histological damages. Our results show that even the lowest environmental dose of cadmium was able to disturb the endogenous antioxidant system in Wistar testis, although an increase in lipid peroxidation was observed only within the group exposed to the highest environmental dose. Despite that no remarkable morphological changes were observed in any group, significant alterations in blood vessel lumen were reported for some cadmium-exposed animals, suggesting that endothelium is one of the primary targets involved in cadmium toxicity.

Association between prenatal exposure to cadmium and atopic dermatitis in infancy.

Our objective was to evaluate the relationship between intrauterine exposure to cadmium and the presence of atopic dermatitis in infants 6 months of age, adjusted for covariates including exposure to other heavy metals. The present research is a component of the Mothers' and Children's Environmental Health (MOCEH) study, a multi-center birth cohort project conducted in Korea. Study subjects were restricted to pregnant women in whom cadmium and lead levels were measured at delivery and whose infants were assessed for the presence of atopic disease at 6 months of age. The odds ratio (OR) for the presence of atopic dermatitis in 6-month-old infants whose cord blood had elevated cadmium levels, after adjustment for other covariates, was 2.350 (95% CI, 1.126-4.906). The OR for the presence of atopic dermatitis in infants whose cord blood had elevated lead levels was not significant. In the present study, the cord blood cadmium level was significantly associated with the presence of atopic dermatitis in 6-month-old infants; this was not true of the cord blood lead level. To the best of our knowledge, this is the first prospective study to show a relationship between prenatal exposure to cadmium and atopic dermatitis in infancy.

Dietary cadmium exposure and prostate cancer incidence: a population-based prospective cohort study.

BACKGROUND: Experimental data convincingly propose the toxic metal cadmium as a prostate carcinogen. Cadmium is widely dispersed into the environment and, consequently, food is contaminated. METHODS: A population-based cohort of 41 089 Swedish men aged 45-79 years was followed prospectively from 1998 through 2009 to assess the association between food frequency questionnaire-based estimates of dietary cadmium exposure (at baseline, 1998) and incidence of prostate cancer (3085 cases, of which 894 were localised and 794 advanced) and through 2008 for prostate cancer mortality (326 fatal cases). RESULTS: Mean dietary cadmium exposure was 19 µg per day±s.d. 3.7. Multivariable-adjusted dietary cadmium exposure was positively associated with overall prostate cancer, comparing extreme tertiles; rate ratio (RR) 1.13 (95% confidence interval (CI): 1.03-1.24). For subtypes of prostate cancer, the RR was 1.29 (95% CI: 1.08-1.53) for localised, 1.05 (95% CI: 0.87-1.25) for advanced, and 1.14 (95% CI: 0.86-1.51) for fatal cases. No statistically significant difference was observed in the multivariable-adjusted risk estimates between tumour subtypes (P(heterogeneity)=0.27). For localised prostate cancer, RR was 1.55 (1.16-2.08) among men with a small waist circumference and RR 1.45 (1.15, 1.83) among ever smokers. CONCLUSION: Our findings provide support that dietary cadmium exposure may have a role in prostate cancer development.

Bradykinin potentiating factor isolated from Buthus occitanus venom has a protective effect against cadmium-induced rat liver and kidney damage.

Bradykinin and its related peptides are widely distributed in venomous animals, including scorpion. A peptide fraction isolated from the venom of the Egyptian scorpion Buthus occitanus was proved to have a bradykinin-potentiating activity. The aim of the present study was conducted to investigate whether the treatment with bradykinin potentiating factor (BPF) offers more beneficial effects in reversing cadmium-induced oxidative stress in rat liver and kidney. Adult male rats, equally divided into control and two treated groups, 10 animals in each group. group (I) was orally given (1 ml) saline and served as a control group; group (II) of rats was given cadmium chloride (4 mg/kg) alone, once daily an oral dose for 7 successive days; group (III) of rats was given ip injection (1 ml) BPF, once daily a dose for 7 successive days prior to CdCl(2) treatment and on the next 7 successive days with the same dose of cadmium as group II. Both organs were subjected to histopathological analysis with the light microscope. The activities of alanine aminotransferase (ALT), asparate aminotransferase (AST) and alkaline phosphatase (ALP) in serum were measured as indicators of the liver function. As parameters of the kidney function, creatinine, uric acid and urea concentrations in serum were determined. Also, malondialdehyde (MDA), reduced glutathione (GSH), super oxide dismutase (SOD) and catalase (CAT) were determined in both tissues. Cd exposure caused a significant decrease or inhibition in the activities of GSH, SOD, and CAT, with significant increase in the level of MDA, in versus to control groups in both liver and kidney. Also, when Cd was treated in co-administration with BPF induced increase or stimulation in the activity of GSH, SOD, and CAT, with significant decrease in the level of MDA when compared to Cd group in both organs. Histopathological changes of liver and kidney were also in accordance with the biochemical findings. Our data showed that Cd treatment induced histopathological alteration in the liver, severe hydropic degeneration in centrolobular zones. Inflammatory cells infiltration around the congested central vein and an obvious injury in some renal tubules. Bradykinin potentiating factor (BPF) administration prevented the histopathological alterations which observed in Cd-groups and both liver and kidney had essentially normal appearance in histopathological examination. In conclusion, BPF markedly ameliorated cadmium-induced liver and kidney tissue damage as evidenced by histological and biochemical examinations and acts as a potent scavenger of free radicals to protect the liver and kidney against the deleterious effect of acute cadmium intoxication.

Cadmium toxicity revisited: focus on oxidative stress induction and interactions with zinc and magnesium.

Discovered in late 1817, cadmium is currently one of the most important occupational and environmental pollutants. It is associated with renal, neurological, skeletal and other toxic effects, including reproductive toxicity, genotoxicity, and carcinogenicity. There is still much to find out about its mechanisms of action, biomarkers of critical effects, and ways to reduce health risks. At present, there is no clinically efficient agent to treat cadmium poisoning due to predominantly intracellular location of cadmium ions. This article gives a brief review of cadmium-induced oxidative stress and its interactions with essential elements zinc and magnesium as relevant mechanisms of cadmium toxicity. It draws on available literature data and our own results, which indicate that dietary supplementation of either essential element has beneficial effect under condition of cadmium exposure. We have also tackled the reasons why magnesium addition prevails over zinc and discussed the protective role of magnesium during cadmium exposure. These findings could help to solve the problem of prophylaxis and therapy of increased cadmium body burden.

Cadmium--is there something to fear?

Cadmium (Cd, cadmium in Latin) is a heavy metal widely present in nature. Like Hg, Pb, and As, cadmium belongs to elements with an unknown physiopathologic role. The progress of civilization, urbanization, and industrialization may lead to significant risk of cadmium pollution in the natural environment. The authors draw attention to the likely causes and effects of environmental pollution with cadmium and its effects on human health. Environmental and occupational exposures are discussed. Strong correlations between cadmium dose, exposure time, tissue concentration, and clinical symptoms in humans are emphasized.

The effects of a vitamin D-deficient diet on chronic cadmium exposure in rats.

Itai-itai disease (IID) of humans is one of the most severe forms of chronic cadmium (Cd) intoxication. Itai-itai disease occurs mainly in post-menopausal women and is characterized by osteoporosis with osteomalacia, renal tubular disorder, and renal anemia. Some researchers insist the major cause of IID is not Cd, but rather malnutrition, especially hypovitaminosis D. We administrated a low concentration of Cd chloride intravenously to ovariectomized female rats that were fed a vitamin D-deficient diet or a normal diet for fifty weeks. The vitamin D-deficient diet decreased serum concentration of vitamin D, but it did not affect the metabolism of the kidney or bone. Cadmium treatment alone induced a decrease in serum concentration of vitamin D, as well as renal dysfunction, renal anemia, and abnormal bone metabolism. Osteoporosis with osteomalacia, tubular nephropathy, fibrous osteodystrophy, and bone marrow hyperplasia occurred following Cd treatment. In rats treated with Cd and administered a vitamin D-deficient diet, the toxic effects of Cd on kidney, bone, and hematopoiesis were enhanced in comparison to rats treated with Cd and a normal diet. The present experiment demonstrated that hypovitaminosis D did not evoke morphologic features of IID in humans but did enhance Cd-induced toxicity in the rat model of this disease.

[Clinical and biochemical syndromes of cadmium-induced acute porphyrinopathy].

AIM: To study the specific features of porphyrin metabolic disturbances in cadmium poisoning. MATERIAL AND METHODS: The paper describes a patient who has developed clinical and biochemical syndromes of acute porphyrinopathy after exposure to cadmium-containing paint the vapors. The levels of delta-aminolevulinic acid, porphobilinogen, coproporphyrin, and uroporphyrin in urine and those of coproporphyrin and protoporphyrin in feces were measured. The concentrations of lead, cadmium, and copper were determined in whole blood and urine; selective screening of amino acids for hereditary metabolic diseases was made. RESULTS: The clinical signs of acute porphyrinopathy developed in the patient mimicked those of acute porphyries known by the current classification. The biochemical syndrome more corresponded to lead poisoning. However, the blood and urinary lead levels were not greater than the normal values, but the blood showed a 4-fold increase in cadmium, which seemed to induce porphyrin dysmetabolism.