Chronic Arsenic Exposure and Blood Glutathione and Glutathione Disulfide Concentrations in Bangladeshi Adults

Abstract

Background: In vitro and rodent studies have shown that arsenic (As) exposure can deplete glutathione (GSH) and induce oxidative stress. GSH is the primary intracellular antioxidant; it donates an electron to reactive oxygen species, thus producing glutathione disulfide (GSSG). Cysteine (Cys) and cystine (CySS) are the predominant thiol/disulfide redox couple found in human plasma. Arsenic, GSH, and Cys are linked in several ways: a) GSH is synthesized via the transsulfuration pathway, and Cys is the rate-limiting substrate; b) intermediates of the methionine cycle regulate both the transsulfuration pathway and As methylation; c) GSH serves as the electron donor for reduction of arsenate to arsenite; and d) As has a high affinity for sulfhydryl groups and therefore binds to GSH and Cys.Objectives: We tested the hypothesis that As exposure is associated with decreases in GSH and Cys and increases in GSSG and CySS (i.e., a more oxidized environment).Methods: For this cross-sectional study, the Folate and Oxidative Stress Study, we recruited a total of 378 participants from each of five water As concentration categories: < 10 (n = 76), 10–100 (n = 104), 101–200 (n = 86), 201–300 (n = 67), and > 300 µg/L (n = 45). Concentrations of GSH, GSSG, Cys, and CySS were measured using HPLC.Results: An interquartile range (IQR) increase in water As was negatively associated with blood GSH (mean change, –25.4 µmol/L; 95% CI: –45.3, –5.31) and plasma CySS (mean change, –3.00 µmol/L; 95% CI: –4.61, –1.40). We observed similar associations with urine and blood As. There were no significant associations between As exposure and blood GSSG or plasma Cys.Conclusions: The observed associations are consistent with the hypothesis that As may influence concentrations of GSH and other nonprotein sulfhydryls through binding and irreversible loss in bile and/or possibly in urine.Citation: Hall MN, Niedzwiecki M, Liu X, Harper KN, Alam S, Slavkovich V, Ilievski V, Levy D, Siddique AB, Parvez F, Mey JL, van Geen A, Graziano J, Gamble MV. 2013. Chronic arsenic exposure and blood glutathione and glutathione disulfide concentrations in Bangladeshi adults. Environ Health Perspect 121:1068–1074; http://dx.doi.org/10.1289/ehp.1205727

Arsenic and the Cardiovascular System

“…In another cross-sectional study, a total of 378 participants from areas with different arsenic water concentrations were recruited and their blood GSH and GSSG were evaluated through HPLC. The results showed that the interquartile range increase in water arsenic was negatively associated with blood GSH and urine arsenic levels [21]. These observations are consistent with other observations in animal studies where arsenic exposure influences GSH levels in blood [22,23].…”

Blood glutathione redox status and global methylation of peripheral blood mononuclear cell DNA in Bangladeshi adults

“…19 Males had higher blood GSH concentrations, less oxidized blood GSH E h values, and higher blood SAM levels than females (p < 0.0001). Eversmokers also had higher GSH concentrations, less oxidized blood GSH E h values, and higher SAM levels than never-smokers.…”

“…Participants were selected based on well water As (wAs) exposure such that the final study sample represented the full range of wAs concentrations in the region, as described previously. 19 Participants were excluded if they were pregnant and/or planned to become pregnant within 3 mo, were currently taking nutritional supplements (within the past 3 mo) or had known diabetes, cardiovascular or renal disease or other diseases known to be associated with oxidative stress.…”

“…Whole blood and plasma GSH and GSSG were assayed by the method of Jones et al, 56 as previously described. 19 Briefly, blood samples were collected in the field laboratory with a butterfly syringe, immediately processed for derivatization, and stored at −80°C until delivered to Columbia University for analysis. Of each sample, 20 μl was injected onto the HPLC, and metabolites were detected using a Waters 474 scanning fluorescence detector with 335 nm excitation and 515 nm emission (Waters Corp.).…”

MS-Based Metabolomics for the Investigation of Neuro-Metabolic Changes Associated with BDE-47 Exposure in C57BL/6 Mice

“…Downstream metabolite, cysteine is regarded as a rate-limiting substrate in glutathione (GSH) biosynthesis [32]. Notably, GSH is known as a principle antioxidant required for liver detoxification reactions.…”