Evaluation of controlled-release devices for providing chromium sesquioxide and zinc in Huacaya alpacas at pasture.

OBJECTIVE: To assess the effectiveness of controlled-release devices (CRDs) for providing zinc and for estimating faecal output in alpacas and sheep at pasture. METHODS: The study groups of 10 alpacas and 10 sheep at pasture were paired within species and allocated at random to receive by mouth either one CRD containing chromium sesquioxide designed to function for at least 21 days or two CRDs, one containing chromium sesquioxide and the other zinc oxide designed to release over a nominal 60-day period. Faecal concentrations of chromium, zinc and ash, blood and plasma concentrations of zinc and plasma activity of alkaline phosphatase (ALP) were measured over a period of 117 days after treatment. RESULTS: The mean faecal chromium excretion profiles suggested that the CRDs performed in a similar manner in both species, releasing chromium for nearly 30 days in alpacas and for slightly more than 30 days in sheep. Using a common predetermined release rate of chromium from the CRDs, the daily faecal outputs of alpacas and sheep were estimated to be 0.54 kg dry matter and 0.33 kg dry matter, respectively. The CRD containing zinc oxide provided after 1 week an estimated daily release rate of 40 mg zinc with a lifetime of between 60 and 70 days in both species. The additional zinc did not elicit a response in blood zinc concentrations or in plasma ALP activity. CONCLUSION: The CRDs were retained in the gastrointestinal tracts of the alpacas and sheep and both types functioned as expected. The CRD delivering chromium sesquioxide at a known release rate provided an estimate of faecal dry matter output over a period of almost 3 weeks and the CRD formulated to deliver supplementary zinc did so at the nominal release rate over a period of approximately 60 days in both species. These data indicated that the standard sheep CRD is applicable for use in alpacas.

Oxidative stress and DNA damage in a long-term hexavalent chromium-exposed population in North China: a cross-sectional study.

OBJECTIVE: The International Agency for Research on Cancer classifies hexavalent chromium (Cr(VI)) as a human carcinogen. As reported, cancer mortality was higher in Cr(VI)-contaminated areas. Scientists have recommended studying its health impact on people living in contaminated areas. This study aims to evaluate the health risk for people living in Cr(VI)-contaminated areas. DESIGN: We conducted a cross-sectional study in rural areas of north-eastern China. Malondialdehyde (MDA), glutathione peroxidase (GSH-Px), superoxide dismutase (SOD) and catalase (CAT) were used as oxidative stress parameters, and 8-hydroxy-2 deoxyguanosine (8-OHdG) as a DNA damage biomarker. We collected information on demographics, lifestyles and length of residence from all participants using a questionnaire. Biological specimens and environmental media samples were collected on the same day as the survey was done. We used t-test, χ2 test, Wilcoxon rank-sum test and multivariate linear regression analysis. PARTICIPANTS: The study included 319 participants exposed to Cr(VI) and 307 unexposed participants, with 447 women and 179 men. These participants met the following criteria: (1) living in the areas for more than 10 years; (2) age older than 18 years; and (3) without occupational chromium exposure. RESULTS: Our study revealed that serum concentration of MDA (p<0.001), serum activities of CAT (p<0.001) and GSH-Px (p<0.001), as well as urine concentration of 8-OHdG (p=0.008) in the exposed group were significantly higher than those in the unexposed group. However, serum SOD activity was significantly lower in the exposed group, compared with that in the unexposed group (p<0.001). Cr(VI) exposure and smoking have an interaction effect on GSH-Px activity (p<0.05). Cr(VI) exposure and alcohol drinking also have an interaction effect on GSH-Px activity (p<0.05). Longer residence in the exposed areas increased the oxidative levels (p<0.05). CONCLUSIONS: The findings of this study showed elevated oxidative stress and DNA damage in people exposed to Cr(VI).

Is the Pharmacological Mode of Action of Chromium(III) as a Second Messenger?

Although recent studies have shown that chromium (as the trivalent ion) is not an essential trace element, it has been demonstrated to generate beneficial effects at pharmacologically relevant doses on insulin sensitivity and cholesterol levels of rodent models of insulin insensitivity, including models of type 2 diabetes. The mode of action of Cr(III) at a molecular level is still an area of active debate; however, the movement of Cr(III) in the body, particularly in response to changes in insulin concentration, suggests that Cr(III) could act as a second messenger, amplifying insulin signaling. The evidence for the pharmacological mechanism of Cr(III)'s ability to increase insulin sensitivity by acting as a second messenger is reviewed, and proposals for testing this hypothesis are described.

Antigenotoxic effects of (-)-epigallocatechin-3-gallate (EGCG), quercetin, and rutin on chromium trioxide-induced micronuclei in the polychromatic erythrocytes of mouse peripheral blood.

This study was conducted to investigate the modulating effects of (-)-epigallocatechin-3-gallate (EGCG), quercetin, and rutin on the genotoxic damage induced by Cr(VI) in polychromatic erythrocytes of CD-1 mice. The animals were divided into the following groups: (i) vehicle only; (ii) flavonoids (10 mg/kg EGCG, 100 mg/kg quercetin, 625 mg/kg rutin, or 100-625 mg/kg quercetin-rutin); (iii) Cr(VI) (20 mg/kg of CrO3); and (iv) flavonoids concomitantly with Cr(VI). All of the treatments were administered intraperitoneally (i.p.). The genotoxic damage was evaluated based on the number of micronucleated polychromatic erythrocytes (MN-PCE) obtained from the caudal vein 0, 24, 48, and 72 h after treatment. Groups treated with EGCG and quercetin exhibited no significant statistical changes in induction of MN-PCE. However, CrO3 treatment significantly increased MN-PCE induction 24 and 48 h after injection. Treatment with flavonoids prior to CrO3 exposure decreased MN-PCE induction compared with CrO3 only. The magnitudes of the potency of flavonoids were in the following order: rutin (82%) > quercetin (64%) > quercetin-rutin (59%) and EGCG (44%). The group treated with rutin significantly reduced genotoxic damage in mice treated with Cr(VI) (antioxidant effect). However rutin exerted a marginal genotoxic effect when administered alone (pro-oxidant effect). Our findings suggest protective effects of EGCG, quercetin, and rutin against genotoxic damage induced by Cr(VI).

Genotoxicity and oxidative stress in chromium-exposed tannery workers in North India.

Trivalent chromium (Cr) is an environmental contaminant, which is extensively used in tanning industries throughout the world and causes various forms of health hazards in tannery workers. Therefore, a cross-sectional study design was used to evaluate the DNA damage and oxidative stress condition in tannery workers exposed to Cr in North India. The study population comprised 100 male tanners in the exposed group and 100 healthy males (no history of Cr exposure) in the comparable control group. Baseline characteristics including age, smoking, alcohol consumption habits and duration of exposure were recorded via interviewing the subjects. Blood Cr level (measured by atomic absorption spectrophotometry), DNA damage (measured by comet assay) and oxidative stress parameters (malondialdehyde (MDA), glutathione (GSH) and superoxide dismutase (SOD)) were estimated in both the groups. As a result of statistical analysis, exposed group showed significantly higher level of Cr (p < 0.0001), DNA damage (p < 0.0001), MDA (p < 0.0001), SOD (p < 0.05) and lower level of GSH (p < 0.001) when compared with controls. Smoking, alcohol consumption habits and age had no significant effect (p > 0.05) on DNA damage and oxidative stress parameters in both the groups. In simple and multiple correlation analysis, DNA damage and oxidative stress parameters showed significant correlation with Cr level and duration of exposure in exposed group. The findings of the present study revealed that chronic occupational exposure to trivalent Cr may cause DNA damage and oxidative stress in tannery workers.

Toxic effects of chromium on tannery workers at Sialkot (Pakistan).

Chromium is widely used in the leather industry, and tannery workers are under constant threat of adverse health effects due to its excessive exposure. Our objective was to find out the toxic effects of chromium on tannery workers at Sialkot, Pakistan. A total of 240 males consisting of 120 workers from tanneries at Sialkot and equal number of controls were included. Blood complete counts, high-sensitive C-reactive protein, malondialdehyde and routine biochemical tests were carried out by routine procedures. Chromium levels in blood (BCr) and urine were analyzed using graphite furnace atomic absorption spectrophotometer Perkin Elmer analyst-200. Results revealed that all the workers were male with average age of 33 years and 15 (13%) had skin rashes, 14 (12%) had chronic bronchitis, 10 (8%) had gastritis and 4 (3%) conjunctivitis. The tannery workers had significantly raised median (interquartile range) of BCr 569 (377-726) nmol/L as compared to 318 (245-397) nmol/L in the control (p < 0.001). Sixty-five (54%) workers had BCr levels above the upper limit set by Agency for Toxic Substance and Drug Registry. The urinary chromium excretion was significantly high in workers 131 (46-312) nmol/L as compared to 13 (3-26) nmol/L in controls (p < 0.01). The workers had hematological, hepatic and renal function impairment because of oxidative stress on body systems. It is concluded that about half of the workers had excessive exposure to chromium in the tanneries at Sialkot. They had significantly raised chromium levels in their biological fluids and adverse health effects due to enhanced oxidative stress and inflammatory changes.

Caveolin-1 as a potential high-risk prostate cancer biomarker.

Current diagnostic techniques of prostate cancer cannot efficiently distinguish the latent and low-risk forms from the high-risk significant forms of prostate cancer. Caveolin-1 (Cav-1), except other functions, plays an important role in cell transformation and the process of tumorigenesis. Furthermore, Cav-1 is involved in metastatic processes. It has also been shown that Cav-1 expression is induced under stress conditions, such as oxidative stress. The present study focused on the determination of prognostic markers of aggressive (high-grade) forms of prostate cancer. We determined serum Cav-1 and serum markers of antioxidant activity-glutathione (GSH), 2,2-diphenyl-1-picrylhydrazyl (DPPH), Trolox equivalent antioxidant capacity (TEAC), ferric-reducing antioxidant power (FRAP), N,N-dimethyl-1,4-diaminobenzene (DMPD), free radicals method (FRK) and blue chromium peroxide (Cro) in 97 serum samples (82 prostate cancer patients and 15 controls). We found insignificant differences in Cav-1 between the sera of patients and controls (5.69 in the cancer group vs. 5.42 ng/ml in the control group). However, we found a significant (p<0.004) 2.8-fold elevation of Cav-1 in high tumour stages (TNM T4) compared to lower stages and a significant positive association with histological grading (r=0.29, p=0.028). We also found that in patients with high serum Cav-1 the antioxidant capacity of the body is reduced. These findings indicate that Cav-1 may be an interesting tool for the prediction of disease burden.

Study on the oxidative stress status among cement plant workers.

The cement industry is considered as a major pollution problem because of dust and particulate matter emitted at various steps of cement production. In the present study, volunteer male workers from a cement factory were studied for oxidative and nitrosative stress biomarkers in relation to their serum levels of aluminum (Al) and chromium (Cr). The subjects were divided into two groups of direct and indirect exposure. Subject who worked in production steps were considered as direct exposure group, and those who worked in administration building were considered as indirect exposure group. For comparison, healthy subjects at the same age and socioeconomic status were tested as a control group. Serum levels of lipid peroxidation (LP), total antioxidant capacity (TAC), total thiol molecules (TTM), and nitric oxide (NO) as well as Al and Cr were measured. The results indicated a significant increase in Al (P = 0.001) and Cr (P = 0.009) levels in direct-exposed workers in comparison to healthy control group. Further, a significant increase in Al (P = 0.002) and Cr (P = 0.009) levels was observed in direct-exposed workers as compared to indirect-exposed one. Serum levels of TTM and TAC were significantly lower in both direct- and indirect-exposed groups in comparison to healthy control group (P = 0.00). Serum TTM and TAC were significantly lower in direct-exposed workers as compared to indirect-exposed ones (P = 0.00 and P = 0.024, respectively). There was no significant difference on the level of LP and NO among groups. A correlation was found between serum level of Cr, TAC, and platelets between direct- and indirect-exposed groups (P < 0.05). Further correlation was found among serum level of Cr and those of TTM, platelets, and chronic disease (P < 0.05). Chronic disease had a significant influence adjusted to other predictor variables on the post-shift values of Al (P < 0.05). Although plasma levels of Al and Cr were found in normal ranges, analyses confirm their role in impairment of TMM and TAC.

Aqueous humor and serum levels of chromium in cataract patients with and without diabetes mellitus.

PURPOSE: To evaluate the aqueous humor and serum levels of chromium (Cr) in cataract patients with and without diabetes mellitus. METHODS: Levels of Cr were measured using atomic absorption spectrometry in the serum from 20 patients and aqueous humor aspirates taken during anterior segment surgery from 20 eyes of 20 patients who had diabetic cataracts and from 20 eyes of 20 patients who had senile cataract only. RESULTS: The mean aqueous humor Cr concentration in eyes with diabetes cataract was significantly lower than that from eyes with senile cataract (p < 0.001). There was also a statistically significant difference between the serum Cr concentrations of the diabetic group and the control group (p < 0.001). CONCLUSION: The aqueous humor and serum Cr levels are decreased in eyes with diabetic cataract.

Assessment of efficacy of quercetin-5'-sulfonic acid sodium salt in the treatment of acute chromium poisoning: experimental studies.

Hexavalent chromium compounds exhibit higher toxicity than its trivalent compounds since chromium ions in the +6 oxidation state easily cross biological membranes. It has recently been proposed that substances reducing chromium ions from the +6 to the less toxic +3 oxidation state can be beneficial in management of acute chromium poisoning. In vitro studies also demonstrated quercetin-5 '-sulfonic acid sodium salt (NaQSA) to reduce chromium ions from the +6 to the +3 oxidation state. The aim of the study was to determine efficacy of NaQSA in treatment of acute poisoning with a hexavalent chromium compound. The experiment was carried out on male and female Wistar rats which were divided into 4 experimental (A,B,C,D) and control (K) groups. All animals received intragastrically a single CrO3 dose equal to its LD50. Thirty minutes after administration of CrO3, NaQSA was administered intragastrically at a dose of 50 mg/kg (group A) and 100 mg/kg (group B). In groups C and D, NaQSA was administered ip 2 h after administration of CrO3 and then twice a day for 4 days at doses of 50 mg/kg (group C) and 100 mg/kg (group D). Only intragastric administration of NaQSA at a dose of 100 mg/kg decreased mortality in acute poisoning with CrO3. In groups B and D, aminotransferase activity was statistically significantly dropping from day 7 of the experiment in comparison with the group K, which indicates lesser damage to the liver in animals treated with NaQSA. Bilirubin concentrations in groups B and D were also much lower than in the group K, but the difference between average bilirubin levels in these groups and the K was not statistically significant. The results of the study suggest the usefulness of NaQSA in the treatment of poisoning with hexavalent chromium compounds.

Endotoxin decreases 51CrCl3 uptake in early weaned pigs.

Endotoxin, a product of bacterial infections, was used to investigate the effects acute infections on chromium (Cr) uptake in early weaned (14 d of age) pigs. At d 18, pigs were anesthetized, and a 2-mm silastic jugular catheter was inserted and passed subcutaneously to a dorsal position behind the ear. At d 21, pigs were deprived of food for 7 h and injected intraperitoneally with saline or 25 microg endotoxin (lipopolysaccharide from Escherichia coli serotype 0111:B4) per kg body wt suspended in 9 g/L saline. One hour after dosing, an oral dose of 0.7 mCi of 51CrCl3 was given by micropipet. Blood was sampled from the catheter at intervals until necropsy at 8 h after the 51CrCl3 dose. Blood and tissue samples were counted in a gamma counter. 51Cr in blood was significantly lower at 3, 4, 5, 6, and at 8 h after dosing in endotoxin-injected pigs compared to controls. Eight hours after 51CrCl3 dosing, 51Cr retention was significantly lower in the liver, heart, and kidney in endotoxin-treated pigs and tended to be lower in spleen (p<0.06) and in urine (p<0.16) with endotoxin treatment. These data suggest that during acute infection, there might be decreased Cr uptake and retention.

Sister chromatid exchange induced by chromium compounds in human lymphocytes.

The objective of this study was to study was to compare chromium (Cr), nickel-chromium (Ni-Cr), and control groups for sister chromatid exchange (SCE) in lymphocytes to obtain an understanding of the mutagenic effect of Cr(VI) in humans. Subjects totaled 91 persons from the 3 groups, including 14 Cr and 34 Ni-Cr electroplating workers and 43 control group members. Results showed that blood and urine Cr concentrations were highest among Cr workers (11.39 microg/l, 14.7 microg/g creatinine), next highest among Ni-Cr workers (5.28 microg/l, 6.2 microg/g creatinine), and lowest among the control group (2.36 microg/l, NA). After adjustment for smoking habits, SCE/cell values were 10.6, 9.4, and 8.3 for Cr workers, Ni-Cr workers, and controls, respectively. A synergetic effect was shown on HFC (high-frequency cells) percentages for Cr workers who also smoked. Odds ratios were 31.78 and 3.66 that Cr and Ni-Cr workers would have higher HFC percentages than the control group, respectively. The authors conclude that SCE in lymphocytes is useful for evaluation of the biological effects of environmental mutagens.

Absorption and elimination of trivalent and hexavalent chromium in humans following ingestion of a bolus dose in drinking water.

These studies investigate the magnitude and valence state of chromium absorbed following plausible drinking water exposures to chromium(VI). Four adult male volunteers ingested a single dose of 5 mg Cr (in 0.5 liters deionized water) in three choromium mixtures: (1) Cr(III) chloride (CrCl3), (2) potassium dichromate reduced with orange juice (cr(III)-OJ); and (3) potassium dichromate [Cr(VI)]. Blood and urine chromium levels were followed for 1-3 days prior to and up to 12 days after ingestion. The three mixtures showed quite different pharmacokinetic patterns. CrCl3 was poorly absorbed (estimated 0.13% bioavailability) and rapidly eliminated in urine (excretion half-life, approximately 10 hr), whereas Cr(III)-OJ was absorbed more efficiently (0.60% bioavailability) but more slowly (half-life, approximately 17 hr), and Cr(VI) had the highest bioavailability (6.9%) and the longest half-life (approximately 39 hr). All three chromium mixtures caused temporary elevations in red blood cell (RBC) and plasma chromium concentrations, but the magnitude and duration of elevation showed a clear trend (Cr(VI) > Cr(III)-OJ > CrCl3). The data suggest that nearly all the ingested Cr(VI) was reduced to Cr(III) before entering the bloodstream based on comparison to RBC and plasma chromium patterns in animals exposed to high doses of Cr(VI). These findings support our prior work which suggests that water-soluble organic complexes of Cr(III) formed during the reduction of Cr(VI) in vivo explain the patterns of blood uptake and urinary excretion in humans at drinking water concentrations of 10 mg/liter or less.

Death by tanning--a case of fatal basic chromium sulphate poisoning.

A woman ingested 400 ml of leather tanning solution containing 48 g of basic chromium sulphate (CrOHSO4). This substance forms hydrogen ions and trivalent chromium when it reacts with tissue proteins. The patient died of cardiogenic shock, complicated by pancreatitis and gut mucosal necrosis and haemorrhage. There are no reported cases of toxicity due to oral ingestion of trivalent chromium. Toxicity of hexavalent and trivalent chromium is discussed and suggestions made for management of future cases.