Arsenic exposure, inflammation, and renal function in Bangladeshi adults: effect modification by plasma glutathione redox potential

Brandilyn A. Peters, Xinhua Liu, Megan N. Hall, Vesna Ilievski, Vesna Slavkovich, Abu B. Siddique, Shafiul Alam, Tariqul Islam, Joseph H. Graziano, Mary V. Gamble

Research output: Contribution to journalArticle

16 Scopus citations

Abstract

Abstract Exposure to arsenic (As) in drinking water is a widespread public health problem leading to increased risk for multiple outcomes such as cancer, cardiovascular disease, and possibly renal disease; potential mechanisms include inflammation and oxidative stress. We tested the hypothesis that As exposure is associated with increased inflammation and decreased estimated glomerular filtration rate (eGFR) and examined whether the effects of As were modified by plasma glutathione (GSH), glutathione disulfide (GSSG), or the reduction potential of the GSSG/2GSH pair (EhGSH). In a cross-sectional study of N = 374 Bangladeshi adults having a wide range of As exposure, we measured markers of inflammation (plasma C-reactive protein (CRP), α-1 acid glycoprotein (AGP)), renal function (eGFR), GSH, and GSSG. In covariate-adjusted models, a 10% increase in water As, urinary As adjusted for specific gravity (uAs), or blood As (bAs) was associated with a 0.74% (p = 0.01), 0.90% (p = 0.16), and 1.39% (p = 0.07) increase in CRP, respectively; there was no association with AGP. A 10% increase in uAs or bAs was associated with an average reduction in eGFR of 0.16 (p = 0.12) and 0.21 ml/min/1.73 m2 (p = 0.08), respectively. In stratified analyses, the effect of As exposure on CRP was observed only in participants having EhGSH > median (uAs pWald = 0.03; bAs pWald = 0.05). This was primarily driven by stronger effects of As exposure on CRP in participants with lower plasma GSH. The effects of As exposure on eGFR were not modified significantly by EhGSH, GSH, or GSSG. These data suggest that participants having lower plasma GSH and a more oxidized plasma EhGSH are at increased risk for As-induced inflammation. Future studies should evaluate whether antioxidant treatment lowers plasma EhGSH and reduces risk for As-induced diseases.

Original languageEnglish (US)
Article number12399
Pages (from-to)174-182
Number of pages9
JournalFree Radical Biology and Medicine
Volume85
DOIs
StatePublished - Jun 16 2015
Externally publishedYes

Keywords

  • Abbreviations AGP α-1 acid glycoprotein
  • BMI body mass index
  • CKD chronic kidney disease
  • CRP C-reactive protein
  • CVD cardiovascular disease
  • EGSH reduction potential of the plasma GSSG/2GSH redox pair
  • FOX Folate and Oxidative Stress study
  • GFR glomerular filtration rate
  • GSH glutathione
  • GSSG glutathione disulfide
  • NF-κB nuclear factor κB
  • ROS reactive oxygen species
  • bAs blood arsenic
  • eGFR estimated glomerular filtration rate
  • uAs urinary arsenic
  • uAs-SG urinary arsenic adjusted for specific gravity
  • wAs water arsenic.

ASJC Scopus subject areas

  • Biochemistry
  • Physiology (medical)

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    Peters, B. A., Liu, X., Hall, M. N., Ilievski, V., Slavkovich, V., Siddique, A. B., Alam, S., Islam, T., Graziano, J. H., & Gamble, M. V. (2015). Arsenic exposure, inflammation, and renal function in Bangladeshi adults: effect modification by plasma glutathione redox potential. Free Radical Biology and Medicine, 85, 174-182. [12399]. https://doi.org/10.1016/j.freeradbiomed.2015.04.020