title: 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.
  
  
  OBJECTIVE
  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.
authors.affiliation: Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, New York, USA.
authors.forename: Megan N
authors.initials: MN
authors.lastname: Hall
authors.forename: Megan
authors.initials: M
authors.lastname: Niedzwiecki
authors.forename: Xinhua
authors.initials: X
authors.lastname: Liu
authors.forename: Kristin N
authors.initials: KN
authors.lastname: Harper
authors.forename: Shafiul
authors.initials: S
authors.lastname: Alam
authors.forename: Vesna
authors.initials: V
authors.lastname: Slavkovich
authors.forename: Vesna
authors.initials: V
authors.lastname: Ilievski
authors.forename: Diane
authors.initials: D
authors.lastname: Levy
authors.forename: Abu B
authors.initials: AB
authors.lastname: Siddique
authors.forename: Faruque
authors.initials: F
authors.lastname: Parvez
authors.forename: Jacob L
authors.initials: JL
authors.lastname: Mey
authors.forename: Alexander
authors.initials: A
authors.lastname: van Geen
authors.forename: Joseph
authors.initials: J
authors.lastname: Graziano
authors.forename: Mary V
authors.initials: MV
authors.lastname: Gamble
mesh_terms: D000328:Adult; D001151:Arsenic / Q000097:blood / Q000378:metabolism / Q000633:toxicity* / Q000652:urine; D001459:Bangladesh; D002851:Chromatography, High Pressure Liquid; D003430:Cross-Sectional Studies; D004781:Environmental Exposure / Q000009:adverse effects*; D005978:Glutathione / Q000097:blood* / Q000378:metabolism; D019803:Glutathione Disulfide / Q000097:blood* / Q000378:metabolism; D006801:Humans; D016014:Linear Models
chemical_list: D005978:Glutathione; D001151:Arsenic; D019803:Glutathione Disulfide