No abstract

Several epidemiological studies have suggested that exposure to arsenic is strongly correlated with the development of cardiovascular diseases such as hypertension. To determine whether arsenic affects vasomotor tone in blood vessels, we investigated the effect of arsenic on vasorelaxation using isolated rat aortic rings in an organ-bath system. Treatment with arsenite inhibited acetylcholine-induced relaxation of the aortic rings in a concentration-dependent manner, whereas several other arsenic species did not have any effect. Consistent with these findings, the levels of guanosine 3',5'-cyclic monophosphate (cGMP) in the aortic rings were significantly reduced by arsenite treatment. In cultured human aortic endothelial cells, treatment with arsenite resulted in a concentration-dependent inhibition of endothelial nitric oxide synthase (eNOS). In addition, higher concentrations of arsenite decreased the relaxation induced by sodium nitroprusside (an NO donor) and 8-Br-cGMP (a cGMP analog) in aortic rings without endothelium. These in vitro results indicate that arsenite is capable of suppressing relaxation in blood vessels by inhibiting eNOS activity in endothelial cells and by impairing the relaxation machinery in smooth muscle cells. In vivo studies revealed that the reduction of blood pressure by acetylcholine infusion was significantly suppressed after arsenite was administered intravenously to rats. These data suggest that an impairment of vasomotor tone due to arsenite exposure may be a contributing factor in the development of cardiovascular disease.

No abstract

The blood Hg level in Korean adults is higher than that in USA and other Western countries, while it is similar to or lower than that in other Asian countries. The blood Hg level is influenced by sociodemographic factors and individual lifestyles including dietary habits. Furthermore, blood Hg is associated with metabolic syndrome, in which Hg exposure may play a role as a possible risk factor for cardiovascular diseases.

Arsenic (As) is a known human carcinogen and widely distributed in the environment. The main route of As exposure in the general population is through food and drinking water. Seafood harvested in Korea contains high-level organoarsenics such as arsenobetaine, arsenocholine, and arsenosugars, which are much less harmful than inorganic arsenics. However, for those who eat large amounts of seafood it is important to understand whether seafood consumption affects urinary levels of inorganic As metabolites such as arsenite, arsenate, monomethylarsonic acid (MMA), and dimethylarsinic acid (DMA). In this study we investigated urinary As metabolites (inorganic As, MMA[V], DMA[V]) and some biological indexes such as AST, GSH, GPX, lipid peroxidation, and uric acid in volunteer study subjects (seven males and nine females). Total urinary As metabolites were analyzed by the hydride generation method, followed by arsenic speciation using HPLC with ICP-mass spectrometry. Study subjects refrained from eating seafood for 3 days prior to the first urine collection and then ingested seafood daily for 6 consecutive days. The first voided urine of the morning was collected from each subject the first day of the consecutive 6 days of seafood ingestion but prior to the first seafood meal. The first voided urine of the morning was also collected on days 1, 2, 3, 4, 5, 6, 7, 10, and 14 after seafood ingestion. The daily mean intake of total As was 6.98 mg, comprised of 4.71 mg of seaweed (67%), 1.74 mg of flat fish (25%), and 0.53 mg of conch (8%). We observed a substantial increase in total urinary As metabolites for subjects consuming seafood from day 1, which recovered to control level at day 10. The increase in total urinary As metabolites was attributed to the increase in DMA, which is a more harmful metabolite than organoarsenics. However, no significant changes in response biological indexes were observed. These results suggest that it is necessary to evaluate As metabolism when assessing the exposure to inorganic As and potential chronic health effects of seafood consumption in Korea.

Iron (Fe) plays essential roles in biological processes, whereas cadmium (Cd) is a toxic and non-essential metal. Two metal transporters, divalent metal transporter 1 (DMT1) and metal transporter protein 1 (MTP1), are responsible for Fe transport in mammals. Here, we studied the effect of dietary Fe on the expression of these metal transporters in peripheral tissues, and the uptake by these tissues of Cd. Mice were fed an Fe-sufficient (FeS: 120 mg Fe/kg) or Fe-deficient (FeD: 2-6 mg Fe/kg) diet for 4 weeks. The total Fe levels in the body were evaluated by measuring tissue Fe concentrations. Tissue Cd concentrations were determined 24 h after the mice received a single oral dose of Cd. Animals fed a FeD diet showed depletion of body Fe levels and accumulated 2.8-fold higher levels of Cd than the FeS group. Quantitative real time RT-PCR revealed that whereas DMT1 and MTP1 were both ubiquitously expressed in all FeS peripheral tissues studied, DMT1 was highly expressed in brain, kidney, and testis, whereas MTP1 was highly expressed in liver and spleen. Depletion of the body Fe stores dramatically upregulated DMT1 and MTP1 mRNA expression in the duodenum as well as moderately upregulating their expression in several other peripheral tissues. The iron response element positive isoform of DMT1 was the most prominently upregulated isoform in the duodenum. Thus, DMT1 and MTP1 may play an important role in not only maintaining Fe levels but also facilitating the accumulation of Cd in the body of mammals.

No abstract

Cadmium (Cd) and arsenic (As) are widely distributed in the environment and are known human carcinogens. Several studies reported that chronic exposure to Cd and As produced renal injuries in humans. As one of the mechanisms, oxidative stress was suggested to play a role in the early process of Cd- and/or As-induced tubular damage in the kidney. This study was performed to evaluate the significance of urinary biomarkers, role of oxidative stress, and effect of coexposure to environmental low-level exposure to Cd and/or As in the general population. Urine samples were collected from 290 adults (86 males and 204 females). Urinary concentrations of Cd and As were measured, and kidney biomarkers of toxicity such as beta(2)-microglobulin and N-acetyl-beta-D-glucosaminidase (NAG) activity determined in urine. Urinary malondialdehyde (MDA) and 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels were measured as oxidative stress indices. The mean concentration of Cd was 1.21 microg/L, 0.84 microg/g creatinine, and As was 5.7 microg/L, 3.95 microg/g creatinine in urine. NAG, MDA, and 8-OHdG were positively correlated with both Cd and As in urine. Positive correlations were also observed between NAG and oxidative indices. The effects of coexposure to Cd and As on biomarkers are more pronounced than for exposure to each metal alone. These findings suggest that chronic exposure to low levels of Cd and/or As might produce tubular damage in the kidney through oxidative stress in humans.