[Recent research progress on natural medicines in treatment of cadmium toxicity].

Cadmium contamination of environment is a subject of serious international concern. Bioaccumulation of cadmium occurs primarily through ingestion of contaminated water and food. Cadmium poisoning came into prominence with the "itai-itai" disease event in Japan in the 1950s. It could also cause damages to liver, kidney, lung and other organs. Thus, the treatment of cadmium poisoning has become a research hotspot. Researchers are trying their best to explore prophylactic and therapeutic medicines for prevention and treatment of cadmium-induced poisoning. So far, chelation therapy, the conventional treatment for heavy metal toxicity, is reported to have a number of safety and efficacy issues. Natural medicines have a variety of advantages such as extensive sources, high safety, less adverse reactions, and thus have great potentials in treating cadmium poisoning. In this review, the progress in the antagonistic effects of natural drugs in cadmium poisoning and their therapeutic mechanisms were summarized in order to provide certain references for the future development and in-depth study of antagonistic substances.

Oral Administration of Probiotics Inhibits Absorption of the Heavy Metal Cadmium by Protecting the Intestinal Barrier.

UNLABELLED: The heavy metal cadmium (Cd) is an environmental pollutant that causes adverse health effects in humans and animals. Our previous work demonstrated that oral administration of probiotics can significantly inhibit Cd absorption in the intestines of mice, but further evidence is needed to gain insights into the related protection mode. The goal of this study was to evaluate whether probiotics can inhibit Cd absorption through routes other than the Cd binding, with a focus on gut barrier protection. In the in vitro assay, both the intervention and therapy treatments of Lactobacillus plantarum CCFM8610 alleviated Cd-induced cytotoxicity in the human intestinal cell line HT-29 and protected the disruption of tight junctions in the cell monolayers. In a mouse model, probiotics with either good Cd-binding or antioxidative ability increased fecal Cd levels and decreased Cd accumulation in the tissue of Cd-exposed mice. Compared with the Cd-only group, cotreatment with probiotics also reversed the disruption of tight junctions, alleviated inflammation, and decreased the intestinal permeability of mice. L. plantarum CCFM8610, a strain with both good Cd binding and antioxidative abilities, exhibited significantly better protection than the other two strains. These results suggest that along with initial intestinal Cd sequestration, probiotics can inhibit Cd absorption by protecting the intestinal barrier, and the protection is related to the alleviation of Cd-induced oxidative stress. A probiotic with both good Cd-binding and antioxidative capacities can be used as a daily supplement for the prevention of oral Cd exposure. IMPORTANCE: The heavy metal cadmium (Cd) is an environmental pollutant that causes adverse health effects in humans and animals. For the general population, food and drinking water are the main sources of Cd exposure due to the biomagnification of Cd within the food chain; therefore, the intestinal tract is the first organ that is susceptible to Cd contamination. Moreover, Cd exposure causes the disruption of the intestinal barrier and further induces the amplification of Cd absorption. The present study confirms that, along with initial intestinal Cd sequestration, oral administration of probiotics can inhibit Cd absorption by protecting the intestinal barrier. A probiotic with both good Cd-binding and antioxidative capacities can be used as a daily supplement for the prevention of oral Cd exposure.

Cadmium toxicity and treatment.

Cadmium is a heavy metal of considerable toxicity with destructive impact on most organ systems. It is widely distributed in humans, the chief sources of contamination being cigarette smoke, welding, and contaminated food and beverages. Toxic impacts are discussed and appear to be proportional to body burden of cadmium. Detoxification of cadmium with EDTA and other chelators is possible and has been shown to be therapeutically beneficial in humans and animals when done using established protocols.

[Analysis of clinical features of mild chronic cadmium poisoning induced by different causes].

OBJECTIVE: To analyze the clinical features of mild chronic cadmium poisoning induced by different causes. METHODS: A total of 90 patients with mild chronic cadmium poisoning, who were hospitalized in our center from 2008 to 2011 and had complete clinical data, were divided into two groups according to the causes of poisoning: environmental pollution group (n = 45) and occupational poisoning group (n = 45). The clinical symptoms, signs, laboratory indices, and treatment outcomes of all patients were analyzed. RESULTS: Compared with the environmental pollution group, the occupational poisoning group had more bone pain, less bone injury (based on imaging findings), and significantly increased abnormal rate of urinary retinol-binding protein (RBP) (P < 0.05); there were no significant differences in urinary ß-2 microglobulin (MG) and urinary microalbumin between the two groups (P > 0.05). Urinary cadmium, urinary RBP, and urinary ß-2 MG had no linear correlation between each other in the two groups. Both groups showed significant changes in urinary cadmium levels after treatment (P < 0.05). CONCLUSION: The clinical features of mild chronic cadmium poisoning induced by various causes are different, and active nutritional support therapy plays a positive role in improving prognosis.

[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.

Heavy Metal Toxicity in Chronic Renal Failure and Cardiovascular Disease: Possible Role for Chelation Therapy.

Exposure to heavy metals is common. This exposure is related to environmental contamination of air, water and soil, occupational exposure, accumulation in food, tobacco, and other factors. Cadmium and lead are notable for their widespread contamination, long-lasting effects in the body, and renal as well as cardiovascular toxicity. Acute toxicity due to high-level exposure, as well as chronic low-level exposure are now well-established pathogenic entities. Both chronic renal failure and ischemic heart disease patients have been treated separately in recent studies with ethylenediaminetetraacetic acid (EDTA) chelation therapy. In patients with chronic kidney disease (serum creatinine: 1.5-4.0 mg/dL) and increased body lead burden, weekly low-dose chelation with calcium EDTA slowed the rate of decline in renal function in patients with diabetes and in non-diabetic patients. In patients with a history of myocardial infarction, the Trial to Assess Chelation Therapy study showed that EDTA chelation decreased the likelihood of cardiovascular events, particularly in patients with diabetes. However, heavy metal levels were not measured in this study. It is clear that more research is needed in this area. There is also a need to more frequently consider and test for the possibility of cadmium and lead toxicity in patients with increased risk, such as those with hypertension, diabetes mellitus, and chronic renal disease.

Extracellular vesicles from human bone marrow mesenchymal stem cells repair organ damage caused by cadmium poisoning in a medaka model.

Treatment modalities for kidney disease caused by long-term exposure to heavy metals, such as cadmium (Cd), are limited. Often, chronic, long-term environmental exposure to heavy metal is not recognized in the early stages; therefore, chelation therapy is not an effective option. Extracellular vesicles (EVs) derived from stem cells have been demonstrated to reduce disease pathology in both acute and chronic kidney disease models. To test the ability of EVs derived from human bone marrow mesenchymal stem cells (hBM-MSCs) to treat Cd damage, we generated a Cd-exposed medaka model. This model develops heavy metal-induced cell damage in various organs and tissues, and shows decreased overall survival. Intravenous injection of highly purified EVs from hBM-MSCs repaired the damage to apical and basolateral membranes and mitochondria of kidney proximal tubules, glomerular podocytes, bone deformation, and improved survival. Our system also serves as a model with which to study age- and sex-dependent cell injuries of organs caused by various agents and diseases. The beneficial effects of EVs on the tissue repair process, as shown in our novel Cd-exposed medaka model, may open new broad avenues for interventional strategies.

[Occupational metal poisoning (author's transl)]. / Berufliche Metallvergiftungen.

The early diagnosis of lead poisoning -- the most common type of occupational metal poisoning -- based on the determination of the haemprecursors coproporphyrin, delta amino laevulinic acid and free erythrocyte protoporphyrin. Treatment with chelating agents increases urinary lead excretion very effectively. Clinical manifestations of mercury poisoning are different with organic and inorganic mercury compounds. Cadmium poisoning results in inhibition of non-specific enzymes. Depending on the mode of exposure, alteration of the epithelium of the renal tubules or skeletal damage is seen. The toxic effects of chromium are primarily due to direct contact and absorption. Chromium is also carcinogenic. The importance of technical prophylaxis is stressed.

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.

Extracorporeal complexation and haemodialysis for the treatment of cadmium poisoning. I. Effects of four chelators on the in vitro elimination of cadmium from human blood.

The effect of ethylenediamine tetraacetic acid (EDTA), glutathione (GSH), citrate and 2,3-dimercaptosuccinic acid (DMSA) on the elimination of cadmium (Cd) from human blood, by complexing haemodialysis, was investigated in vitro. A significant increase in elimination rate was observed with all four chelators compared to that observed without chelators. EDTA was found to be the most effective agent, which at a level of 0.01M in the dialysate facilitated elimination of 80% of the blood Cd originally present.

Role of dietary calcium and calcium binding protein in cadmium toxicity in rats.

Growing male rats were fed a purified diet containing 0.6% Ca (two groups) or 0.1% Ca (two groups) for 8 weeks. One 0.6% Ca group and one 0.1% Ca group received 25 ppm Cd (as CdC12) in the drinking water. Diets were fed on an equalized basis with the 0.1% Ca + Cd group determining the amount of diet fed to the other groups. Water was provided ad libitum. Terminal body weights were not different among the four groups. Packed cell volumes were depressed in the Cd-exposed groups, especially the 0.1% Ca + Cd group. The highest concentrations of Cd were found in the lungs, liver, and kidneys of the 0.1% Ca + Cd group. More Cd was bound to low molecular weight proteins of the intestinal mucosa from the 0.1% Ca + Cd group than the 0.6% Ca + Cd group. Rats fed the 0.1% Ca diet appeared to have a greater capacity to absorb either Ca or Cd than rats fed the 0.6% Ca diet, as shown by an enhanced binding of 45Ca and 115mCd to intestinal calcium-binding protein (CaBP) in the rats fed the low calcium diet. A portion of the mucosal Cd was accounted for as Cd bound to metallothionein. It was concluded, based upon these experiments, that cadmium retention and signs of toxicity are enhanced by feeding low Ca diet and that the increased CaBP activity due to Ca restrictions is responsible for the increased Cd uptake observed.