Effect of selenite on the disposition of arsenate and arsenite in rats

Department of Pharmacology and Pharmacotherapy, University of Pécs, Medical School, Szigeti út 12, H-7643, Pécs, Hungary.
Toxicology (Impact Factor: 3.62). 05/2003; 186(1-2):33-50. DOI: 10.1016/S0300-483X(02)00604-2
Source: PubMed


Selenite (SeIV) and inorganic arsenicals counter the toxicity of each other. SeIV inhibits arsenic methylation in hepatocytes, however, it is unknown whether it decreases the formation of the highly toxic monomethylarsonous acid (MMAsIII). Therefore, we examined, in comparison with the methylation inhibitor periodate-oxidised adenosine (PAD), the effect of SeIV (10 micromol/kg, i.v.) on the appearance of arsenic metabolites in blood, bile and urine as well as the distribution of arsenic metabolites in the liver and kidneys in rats injected i.v. with 50 micromol/kg arsenite (AsIII) or arsenate (AsV). Arsenic metabolites were analysed by HPLC-hydride generation-atomic fluorescence spectrometry (HPLC-HG-AFS). In rats given either arsenical, PAD decreased the excretion and tissue concentrations of methylated arsenic metabolites (MMAsIII, monomethylarsonic acid [MMAsV], and dimethylarsinic acid [DMAsV]), while increasing the tissue retention of AsV and AsIII. The effect of SeIV on arsenic disposition differed significantly from that of PAD. For example, both in AsIII- and AsV-injected animals, SeIV lowered the tissue levels of MMAsIII and MMAsV, but increased the levels of DMAsV. SeIV almost abolished the biliary excretion of MMAsIII in AsV-exposed rats, but barely influenced it in AsIII-dosed rats. The SeIV-induced changes in arsenic disposition may largely be ascribable to formation of the known complex containing trivalent arsenic and selenide (SeII), which not only depends on but also influences the availability and effects of these metalloid species in tissues. By such complexation SeII compromises monomethylation of arsenic when trivalent arsenic availability is limited (e.g. in AsV-exposed rats), but affects it less when the presence of AsIII is overwhelming (e.g. in AsIII-dosed rats). As an auxiliary finding, it is shown that DMAsV occurs in the blood of rats not injected with arsenic and that DMAsV formation in rats can be followed by measuring the build-up of blood-borne DMAsV.

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    • "Toxicity due to trivalent arsenic might be attributed to direct binding with the -SH group [3]. In addition, zinc and selenium are essential for the activity of many enzymes that defend biological systems against damage caused by activated oxygen [10,11]. Recent advances have shown that supplemental sulfhydryl (thiol), zinc or selenium can act as complimentary chelator (adjuvant) agents, increasing the efficacy of known chelators, or by acting independently [12, 23,24]. "
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    ABSTRACT: Arsenic, which causes human carcinogenicity, is ubiquitous in the environment. This study was designed to evaluate modulation of arsenic induced cancer by resveratrol, a phytoalexin found in vegetal dietary sources that has antioxidant and chemopreventive properties, in arsenic trioxide (As2O3)-induced Male Wistar rats. Adult rats received 3 mg/kg As2O3 (intravenous injection, iv.) on alternate days for 4 days. Resveratrol (8 mg/kg) was administered (iv.) 1 h before As2O3 treatment. The plasma and homogenization enzymes associated with oxidative stress of rat kidneys were measured, the kidneys were examined histologically and trace element contents were assessed. Rats treated with As2O3 had significantly higher oxidative stress and kidney arsenic accumulation; however, pretreatment with resveratrol reversed these changes. In addition, prior to treatment with resveratrol resulted in lower blood urea nitrogen, creatinine and insignificant renal tubular epithelial cell necrosis. Furthermore, the presence of resveratrol preserved the selenium content (0.805 ± 0.059 µg/g) of kidneys in rats treated with As2O3. However, resveratrol had no effect on zinc level in the kidney relative to As2O3-treated groups. Our data show that supplementation with resveratrol alleviated nephrotoxicity by improving antioxidant capacity and arsenic efflux. These findings suggest that resveratrol has the potential to protect against kidney damage in populations exposed to arsenic.
    Nutrition research and practice 04/2014; 8(2):220-6. DOI:10.4162/nrp.2014.8.2.220 · 1.44 Impact Factor
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    • "The arsenic contents in cardiac tissues of all rats were analyzed following the method in the literature [18] with an atomic fluorescence spectrometry system (AFS930; Beijing Jitian Instrument Co. Ltd., Beijing, China). "
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    ABSTRACT: Arsenic trioxide (As2O3) shows substantial anticancer activity in patients with acute promyelocytic leukemia (APL). Unfortunately, limiting the application of this effective agent to APL patients is severe cardiotoxicity. Resveratrol, the natural food-derived polyphenolic compound, is well known for its antioxidant properties and protects the cardiovascular system. But the potential role of resveratrol against As2O3 in heart via nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) is unclear. The present study evaluated the effects of pretreatment with resveratrol and As2O3 on oxidative stress and cardiac dysfunction in rat. In the present study, resveratrol decreased As2O3-induced reactive oxygen species generation, oxidative DNA damage, and pathological alterations. In addition, cardiac dysfunction parameters, intracellular calcium and arsenic accumulation, glutathione redox ratio, and cAMP deficiency levels were observed in As2O3-treated rats; these changes were attenuated by resveratrol. Furthermore, resveratrol significantly prohibited the downregulation of both Nrf2 and HO-1 gene expressions that were downregulated by As2O3, whereas resveratrol did not alter As2O3-induced nitric oxide formation. Thus, the protective role of resveratrol against As2O3-induced cardiotoxicity is implemented by the maintenance of redox homeostasis (Nrf2-HO-1 pathway) and facilitating arsenic efflux. Our findings suggest coadministration with resveratrol, and As2O3 might provide a novel therapeutic strategy for APL.
    Evidence-based Complementary and Alternative Medicine 11/2013; 2013(11):407839. DOI:10.1155/2013/407839 · 1.88 Impact Factor
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    • "2011 ) . Earlier reports suggest antago - nistic roles between As and Se ( Levander 1977 ) , such that As and Se may reduce each other ' s toxicity by affecting biotransforma - tion , distribution , and excretion ( Csanaky and Gregus 2003 ; Kenyon et al . 1997 ) . "
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    ABSTRACT: Several reports indicate that drinking water arsenic (WAs) and manganese (WMn) are associated with children's intellectual function. Very little is known, however, about possible associations with other neurologic outcomes such as motor function. We investigated the associations of WAs and WMn with motor function in 304 children in Bangladesh, 8-11 years of age. We measured As and Mn concentrations in drinking water, blood, urine, and toenails. We assessed motor function with the Bruininks-Oseretsky test, version 2, in four subscales-fine manual control (FMC), manual coordination (MC), body coordination (BC), and strength and agility-which can be summarized with a total motor composite score (TMC). REsults: Log-transformed blood As was associated with decreases in TMC [β = -3.63; 95% confidence interval (CI): -6.72, -0.54; p < 0.01], FMC (β = -1.68; 95% CI: -3.19, -0.18; p < 0.05), and BC (β = -1.61; 95% CI: -2.72, -0.51; p < 0.01), with adjustment for sex, school attendance, head circumference, mother's intelligence, plasma ferritin, and blood Mn, lead, and selenium. Other measures of As exposure (WAs, urinary As, and toenail As) also were inversely associated with motor function scores, particularly TMC and BC. Square-transformed blood selenium was positively associated with TMC (β = 3.54; 95% CI: 1.10, 6.0; p < 0.01), FMC (β = 1.55; 95% CI: 0.40, 2.70; p < 0.005), and MC (β = 1.57; 95% CI: 0.60, 2.75; p < 0.005) in the unadjusted models. Mn exposure was not significantly associated with motor function. Our research demonstrates an adverse association of As exposure and a protective association of Se on motor function in children.
    Environmental Health Perspectives 07/2011; 119(11):1665-70. DOI:10.1289/ehp.1103548 · 7.98 Impact Factor
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