Aging erythrocyte membranes as biomimetic nanometer carriers of liver-targeting chromium poisoning treatment.

Chromium poisoning has become one of the most common heavy metal poisoning occupational diseases with high morbidity and mortality. However, most antidotes detoxify the whole body and are highly toxic. To achieve hepato-targeted chromium poisoning detoxification, a novel hepato-targeted strategy was developed using aging erythrocyte membranes (AEMs) as biomimetic material coated with a dimercaptosuccinic acid (DMSA) nanostructured lipid carrier to construct a biomimetic nano-drug delivery system. The particle size, potential, drug loading, encapsulation rate, in vitro release, and stability of the nanoparticles (NPs) were characterized. Confocal microscopy and flow cytometry showed that the prepared NPs could be phagocytized by RAW264.7 macrophage cells. The efficacy of AEM-DMSA-NPs for targeted liver detoxification was evaluated by in vitro MTT analysis and an in vivo model of chromium poisoning. The results showed that the NPs could safely and efficiently achieve targeted liver chromium poisoning detoxification. All the results indicated that the biomimetic nano-drug delivery system mediated by aging erythrocyte membranes and containing DMSA nanoparticles could be used as a novel therapeutic drug delivery system potentially targeting liver detoxification.

N-acetylcysteine and ascorbic acid therapy for acute hepatic injury after hexavalent chromium ingestion.

WHAT IS KNOWN AND OBJECTIVE: Hexavalent (VI) chromium is a powerful oxidant that can produce cellular oxidative stress and multi-organ system dysfunction. The role of antioxidants such as N-acetylcysteine (NAC) and ascorbic acid in alleviating organ damage in humans remains unclear. CASE DESCRIPTION: We present a 47-year-old male who ingested 30 mL of plating solution and developed hepatic injury. He was treated with NAC and ascorbic acid with improvement in hepatic function. However, his clinical conditions and jaundice worsened again after discontinuing these therapies. WHAT IS NEW AND CONCLUSION: Our findings suggest a potential role for antioxidant therapy for acute hexavalent chromium poisoning.

[Clinical analysis of 24 cases of occupational chromium rhinopathy].

Occupational chromium rhinopathy is chronic nasal damage caused by chromic anhydride, chromate and dichromate 6-valent chromium compounds. In 2016, 700 people who were exposed to chromium slag in steel plant were checked out. 24 people were found to have nasal injuries. The expert group confirmed 1 case of occupational severe chromium rhinosis and 23 cases of occupational mild chromium rhinosis.There was no significant difference in the incidence, type of work and duration of injury among 24 patients (P>0.05) . Active measures should be taken to prevent chromium rhinopathy and the technological process should be reformed. Occupational health education and occupational health monitoring should be strengthened to avoid exposure of chromium and its compounds through nose and respiratory tract, and to reduce or eliminate the occurrence of chromium rhinosis.

Transcriptome analysis reveals the molecular mechanism of hepatic metabolism disorder caused by chromium poisoning in chickens.

Chromium (Cr) is one of the most important environmental pollutants which are released into the environment due to their wide usage in numerous industries. The excess of Cr (VI) can induce hepatotoxicity, while the molecular mechanism that is involved in Cr (VI)-induced hepatotoxicity is unclear. We demonstrated the induction of chromium poisoning model in chickens to identify the differentially expressed genes (DEGs), and their functions were analyzed under different physiological and pathological conditions. Histopathological examination and transcriptome data for chromium-poisoned livers and control livers were annotated with Illumina® HiSeq 2000. The histopathological examination in chromium poisoning groups showed diapedesis, hemolysis, degeneration, nucleus pycnosis, and central phlebectasia in the liver. A total of 334 genes were upregulated and 509 genes were downregulated. The most strongly upregulated genes were HKDC1, DDX4, ACACA, FDFT1, CYYR1, PPP1R3C, and SLC16A14, while the most downregulated genes were MYBPC3, CCKAR, PCK1, and CPT1A. A Gene Ontology (GO) term with the highest enrichment of DEGs is small molecule metabolic process. In cell component domain, the term with the highest enrichment is extracellular matrix. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways showed that glucose metabolism, lipid metabolism, and protein metabolism were the most important metabolic pathways in the liver. The current study first time provides important clues and evidence for identifying the differentially expressed genes in livers due to Cr (VI)-induced liver injury in chickens.

Severe metallosis and elevated chromium in serum following implantation of the joint unloading implant system.

In recent years, the minimally invasive joint-preserving implant system has been developed. The main goal of this device is to unload the medial knee compartment without affecting the lateral compartment. The current authors describe a severe metallosis and elevated chromium in serum following implantation of the joint unloading implant system of a 50-year-old male patient, presented to our hospital 3 years after implantation of a KineSpring System into his left knee due to unicompartmental medial osteoarthritis (OA) in an external hospital. Radiographs showed radiological signs for loosening of the screws in the tibia and a progressive OA on the medial and patellofemoral compartments. Revision surgery with removing of the unloading device was performed at our hospital. The intraoperative situs presented a severe metallosis around the device. Five days after revision surgery, the laboratory parameters revealed an elevated value for chromium in serum, while nickel and cobalt values in serum were normal. Reliable clinical data about the long-term results of the KineSpring System is desperately needed. Further studies are warranted to work out the effects of cobalt and chromium levels and further side effects following the implantation of the extra-articular absorber system.

Metal-on-Metal Hip Joint Prostheses: a Retrospective Case Series Investigating the Association of Systemic Toxicity with Serum Cobalt and Chromium Concentrations.

INTRODUCTION: There have been concerns about prosthesis failure and the potential for systemic toxicity due to release of cobalt and chromium from metal-on-metal hip joint prostheses (MoM-HP). There is conflicting evidence on whether there is a correlation between higher cobalt and chromium concentrations and systemic toxicity. METHODS: We undertook a retrospective review of consecutive patients with MoM-HP referred for outpatient review in toxicology clinics in London, UK, and in the USA recorded in the Toxicology Investigators Consortium (ToxIC) Registry from June 2011 to June 2015. RESULTS: Thirty-one cases were identified; the median (IQR) serum cobalt concentration was 10.0 (3.8-32.8) mcg/L, and the median (IQR) serum chromium concentration was 6.9 (3.7-18.7) mcg/L. Twenty-three (74.2%) had symptoms, most commonly lethargy, hearing loss, and tinnitus. The odds ratios of symptomatic/asymptomatic patients for metal ion concentrations above/below 7 mcg/L were 1.87 (95% CI 0.37-9.57, p = 0.45) and 0.60 (95% CI 0.10-3.50, p = 0.57) for cobalt and chromium, respectively. Two (6.5%) patients with systemic cobalt toxicity had median (IQR) serum cobalt concentrations significantly higher than those without systemic features (630.4 [397.6-863.2] mcg/L versus 9.8 [2.9-16.4] mcg/L; p = 0.017). However, overall, there were no differences between cobalt (p = 0.38) or chromium (p = 0.92) concentrations between symptomatic and asymptomatic patients and no clinical features or investigation results correlated with cobalt or chromium concentration. CONCLUSION: Two (6.5%) of 31 individuals referred for assessment of MoM-HP were diagnosed with systemic cobalt toxicity. However, despite a high prevalence of reported symptoms, neither symptoms nor investigation results correlated with serum cobalt or chromium concentrations.

Do Dietary Habits Influence Trace Elements Release from Fixed Orthodontic Appliances?

The objective was to investigate the effect of dietary habits on the release of Cr and Ni ions from orthodontic appliances by hair mineral analysis. Patients (N = 47) underwent electronic questionnaire survey to investigate the effect of dietary habits on Cr and Ni levels in hair. The research was carried out on hair sampled at the beginning and in the 4th, 8th, and 12th months of the treatment. The content of Cr and Ni in the collected samples was determined by ICP-OES. The study showed that consumption of acidic dietary products may have the effect on increasing the release of Cr and Ni ions from orthodontic appliances. The release of Cr from orthodontic appliances in patients who consumed fruit juice, coffee, yoghurt, and vinegar was higher. The coefficients enabling comparison of metal ions release pattern at a given sampling points were defined. The comparison of the coefficients yielded the information on the possible magnification of metal ions released as the result of the additional factor consumption of acidic food or drink that intensifies metal ions release. The following magnification pattern was found for chromium: coffee (7.57 times) > yoghurt (2.53) > juice (1.86) > vinegar (1.08), and for nickel: vinegar (2.2) > coffee (1.22) > juice (1.05). Yoghurt did not intensify the release of nickel. Concluding, orthodontic patients should avoid drinking/eating coffee, yoghurt, fruit juices, and vinegar.

Application of ICP-MS and HPLC-ICP-MS for diagnosis and therapy of a severe intoxication with hexavalent chromium and inorganic arsenic.

ICP-MS and HPLC-ICP-MS were applied for diagnosis and therapeutic monitoring in a severe intoxication with a liquid containing hexavalent chromium (Cr(VI)) and inorganic arsenic (iAs). In this rare case a liver transplantation of was considered as the only chance of survival. We developed and applied methods for the determination of Cr(VI) in erythrocytes and total chromium (Cr) and arsenic (As) in blood, plasma, urine and liver tissue by ICP-MS. Exposure to iAs was diagnosed by determination of iAs species and their metabolites in urine by anion exchange HPLC-ICP-MS. Three days after ingestion of the liquid the total Cr concentrations were 2180 and 1070µg/L in whole blood and plasma, respectively, and 4540µg/L Cr(VI) in erythrocytes. The arsenic concentration in blood was 206µg/L. The urinary As species concentrations were <0.5, 109, 115, 154 and 126µg/L for arsenobetaine, As(III), As(V), methylarsonate (V) and dimethylarsinate (V), respectively. Total Cr and As concentrations in the explanted liver were 11.7 and 0.9mg/kg, respectively. Further analytical results of this case study are tabulated and provide valuable data for physicians and toxicologists.

Effects of the Oral Administration of K2Cr2O7 and Na2SeO3 on Ca, Mg, Mn, Fe, Cu, and Zn Contents in the Heart, Liver, Spleen, and Kidney of Chickens.

This study aimed to investigate the effects of selenium on the ion profiles in the heart, liver, spleen, and kidney through the oral administration of hexavalent chromium. Approximately 22.14 mg/kg b.w. K2Cr2O7 was added to water to establish a chronic poisoning model. Different selenium levels (0.00, 0.31, 0.63, 1.25, 2.50, and 5.00 mg Na2SeO3/kg b.w.) around the safe dose were administered to the experimental group model. Ca, Mg, Mn, Fe, Cu, and Zn were detected in the organs through flame atomic absorption spectrometry after these organs were exposed to K2Cr2O7 and Na2SeO3 for 14, 28, and 42 days. Results showed that these elements exhibited various changes. Ca contents declined in the heart, liver, and spleen. Ca contents also decreased on the 28th day and increased on the 42nd day in the kidney. Mn contents declined in the heart and spleen but increased in the kidney. Mn contents also decreased on the 28th day and increased on the 42nd day in the liver. Cu contents declined in the heart and spleen. Cu contents increased on the 28th day and decreased on the 42nd day in the liver and kidney. Zn contents declined in the heart and spleen. Zn contents increased on the 28th day and decreased on the 42nd day in the liver and kidney. Fe contents decreased in the heart and liver. Fe contents increased on the 28th day and decreased on the 42nd day in the spleen and kidney. Mg contents did not significantly change in these organs. Appropriate selenium contents enhanced Mn and Zn contents, which were declined by chromium. Conversely, appropriate selenium contents reduced Ca, Fe, and Cu contents, which were increased by chromium. In conclusion, the exposure of chickens to K2Cr2O7 induced changes in different trace elements, and Na2SeO3 supplementation could alleviate this condition.

Content of trace elements and chromium speciation in Neem powder and tea infusions.

Total concentrations of selected trace elements in Neem powder and in Neem tea were determined by inductively coupled plasma mass spectrometry (ICP-MS). The data revealed that despite high total concentrations of the potentially toxic elements Al and Ni in Neem powder, their amounts dissolved in Neem tea were low. Total concentrations of the other toxic elements Pb, As and Cd were also very low and do not represent a health hazard. In contrast, total concentrations of the essential elements Fe, Cu, Zn, Se Mo and Cr in Neem powder were high and also considerable in Neem tea. Consuming one cup of Neem tea (2g per 200 mL of water) covers the recommended daily intakes for Cr and Se and represents an important source of Mo and Cu. Speciation analysis of Cr by high performance liquid chromatography (HPLC) coupled to ICP-MS with the use of enriched Cr isotopic tracers to follow species interconversions during the analytical procedure demonstrated that toxic Cr(VI) was not present either in Neem powder or in Neem tea. Its concentrations were below the limits of detection of the HPLC-ICP-MS procedure applied. The speciation analysis data confirmed that even Cr(VI) was added, it was rapidly reduced by the presence of antioxidants in Neem leaves. By the use of enriched Cr isotopic spike solutions it was also demonstrated that for obtaining reliable analytical data it is essential to apply the extraction procedures which prevent Cr species interconversions, or to correct for species transformation.

[Heavy metal poisoning and renal injury in children].

Along with global environmental pollution resulting from economic development, heavy metal poisoning in children has become an increasingly serious health problem in the world. It can lead to renal injury, which tends to be misdiagnosed due to the lack of obvious or specific early clinical manifestations in children. Early prevention, diagnosis and intervention are valuable for the recovery of renal function and children's good health and growth. This paper reviews the mechanism of renal injury caused by heavy metal poisoning in children, as well as the clinical manifestations, diagnosis, and prevention and treatment of renal injury caused by lead, mercury, cadmium, and chromium.

Outline of occupational chromium poisoning in China.

The present study analyzed the feature of occupational chromium poisoning in China since the 1980s. The collected data were acquired from 18 previous surveys of chromium poisoning in 14 cities of China. The method of risk assessment was applied to calculate the relative risk and 95% CI, p < 0.05 was considered as a significant risk. The results showed that nasal disease was the most common sign of occupational chromium poisoning, and the prevalence rate of nasal disease was 17.83% in total population of 6,998. Further, the risk analysis showed that occupational chromium poisoning led to an increased risk of lung or liver cancer in male workers due to the definite carcinogenicity of hexavalent chromium. Significantly, an increased risk of spontaneous or threatened abortion was also found in female workers. In conclusion, these studies suggest that early detection of impaired reproductive function or impaired lung or liver function in female or male workers is essential for controlling occupational chromium poisoning in China.

Assessment of the mode of action underlying development of rodent small intestinal tumors following oral exposure to hexavalent chromium and relevance to humans.

Abstract Chronic exposure to high concentrations of hexavalent chromium (Cr(VI)) in drinking water causes intestinal adenomas and carcinomas in mice, but not in rats. Cr(VI) causes damage to intestinal villi and crypt hyperplasia in mice after only one week of exposure. After two years of exposure, intestinal damage and crypt hyperplasia are evident in mice (but not rats), as are intestinal tumors. Although Cr(VI) has genotoxic properties, these findings suggest that intestinal tumors in mice arise as a result of chronic mucosal injury. To better understand the mode of action (MOA) of Cr(VI) in the intestine, a 90-day drinking water study was conducted to collect histological, biochemical, toxicogenomic and pharmacokinetic data in intestinal tissues. Using MOA analyses and human relevance frameworks proposed by national and international regulatory agencies, the weight of evidence supports a cytotoxic MOA with the following key events: (a) absorption of Cr(VI) from the intestinal lumen, (b) toxicity to intestinal villi, (c) crypt regenerative hyperplasia and (d) clonal expansion of mutations within the crypt stem cells, resulting in late onset tumorigenesis. This article summarizes the data supporting each key event in the MOA, as well as data that argue against a mutagenic MOA for Cr(VI)-induced intestinal tumors.

[Worldwide cancer mortality among chromium platers].

The elevated risk of lung cancer among chromate-producing workers has been confirmed by many epidemiological studies. Although chromium has been most used in the chromium plating industry and many platers are employed in small-scale factories, cancer studies have been documented in only a few investigations. We have conducted several prospective cohort studies in Japanese chromium platers and recently extended them through 2003. We additionally surveyed epidemiological studies among chromium platers carried out in other parts of the world. Occupational chromium exposure through chromium plating work may be a risk factor for mortality not only from lung cancer but also malignant lymphoma and brain tumor. The age at first exposure to chromium may be a more important factor than the duration of exposure for an increased risk of lung cancer and malignant lymphoma.

[Re-evaluation of the fundamentals of trace elements].

The roles of trace elements have been extensively studied for decades. However, recent advances in both molecular and epidemiological studies on trace elements have provided new information and concepts on the actions of trace elements. Some of our fundamental knowledge on the roles of trace elements based on classical data should be replaced by new concept based on new findings. This series of "Re-evaluation of the Fundamentals of Trace Elements" aims to provide new fundamentals on trace elements by reviewing rapidly advancing knowledge in this study area. The first article is a critical review on the role of chromium in human nutrition.

Effects of chronic chromium(vi) exposure on blood element homeostasis: an epidemiological study.

One hundred chromate production workers chronically exposed to low-level of hexavalent chromium [Cr(vi)] and eighty healthy individuals free from Cr exposure were recruited to the study. Personal sampling of airborne Cr was conducted and Cr content was quantified by Flame Atomic Absorption Spectrometry (FAAS). At the end of the sampling shift, blood samples were collected and element concentrations were measured by inductively coupled plasma mass spectrometry (ICP-MS) for Cr, Cd, Cu, Mo and Se and inductively coupled plasma atomic emission spectrometry (ICP-AES) for Ca, Fe, Mg and Zn. According to our results, 90% of the chromate production workers were exposed to airborne Cr in a concentration lower than 50 µg m(-3), which is the threshold limit value recommended by the American Conference of Governmental Industrial Hygienists and Chinese Ministry of Health. After Cr(vi) exposure, a significant increase in blood Cr, Cd, Fe, Mg, Mo, Se and Zn concentrations was observed, as well as a significant decrease in Ca concentration. A decrease in blood Cu was only observed among female workers. Blood Cr concentrations of the exposed workers (median = 15.68 ng mL(-1)) was four times higher than that of the controls (median = 3.03 ng mL(-1)), and significantly correlated with airborne Cr (r = 0.568, P<0.001). In addition, the inter-element correlations exhibited significant differences between the two groups. Our findings of the related health effects suggested that the underlying mechanisms of chronic Cr(vi) exposure on blood element homeostasis might be partly explained by oxidative stress in the body, dysfunction of Fe metabolism and renal injury.

Effect of nickel and chromium exposure on buccal cells of electroplaters.

The electroplating industry commonly involves the use of nickel and chromium. An assessment of the genotoxic effects of these metals can be carried out by micronucleus (MN) test in buccal cells. Other nuclear anomalies (NA) observed in buccal cells viz., karyorrhexis, pyknosis and karyolysis are also the indicators of genotoxicity. The current study aims at determining the extent of genotoxic damage in relation to the duration of exposure to nickel and hexavalent chromium via micronuclei induction and other nuclear anomalies. The present investigation included 150 subjects of which 50 individuals with no history of nickel/chromium exposure (Group I) were taken as control, 50 electroplaters exposed to nickel and hexavalent chromium for duration of less than 10 years (Group II) and 50 electroplaters exposed for ≥10 years (Group III) were included. Slides of buccal cells were prepared and the frequency of MN (‰) and NA (‰) were calculated. ANOVA was applied to test significance. Results were considered significant at p < 0.05 and p < 0.001. Group III showed the highest MN frequency (1.08 ± 0.54‰, p < 0.05), karyorrhexis (20.75 ± 6.29, p < 0.05), karyolysis (3.50 ± 1.91, p < 0.001), binucleate (4.75 ± 2.75, p < 0.05) and enucleated cells (5.75 ± 1.70, p < 0.05). Significant increase in frequencies between Group II and III was found as duration of exposure increased. Plasma nickel and chromium levels were also determined which showed a positive correlation with frequency MN and other nuclear abnormalities (p < 0.01).

Blood chromium levels of children working in gem-polishing industries in India.

The gem-polishing industry in Jaipur, India employs a substantial proportion of children. The process of polishing may result in exposure to chromium in working children. Thus, this study aims to find out the levels of chromium in these working children and the associated factors. Blood samples were analysed for chromium using atomic absorption spectrophotometer. The mean blood chromium levels were 2.51 ± 1.11 mg/100 ml and 2.33 ± 1.10 mg/100 ml in working and school children, respectively, which is well within the permissible levels. However, the practice of employing children should be totally curbed.