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

15 Citations (Scopus)

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

Fingerprint

Arsenic
Oxidation-Reduction
Glutathione
Inflammation
Kidney
Plasmas
Glutathione Disulfide
Glomerular Filtration Rate
C-Reactive Protein
Blood
Glycoproteins
Specific Gravity
Acids
Oxidative stress
Public health
Medical problems
Drinking Water
Density (specific gravity)
Blood Proteins
Oxidative Stress

Keywords

  • Abbreviations AGP α-1 acid glycoprotein
  • bAs blood arsenic
  • 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
  • eGFR estimated glomerular filtration rate
  • FOX Folate and Oxidative Stress study
  • GFR glomerular filtration rate
  • GSH glutathione
  • GSSG glutathione disulfide
  • NF-κB nuclear factor κB
  • ROS reactive oxygen species
  • uAs urinary arsenic
  • uAs-SG urinary arsenic adjusted for specific gravity
  • wAs water arsenic.

ASJC Scopus subject areas

  • Biochemistry
  • Physiology (medical)

Cite this

Arsenic exposure, inflammation, and renal function in Bangladeshi adults : effect modification by plasma glutathione redox potential. / Peters, Brandilyn A.; Liu, Xinhua; Hall, Megan N.; Ilievski, Vesna; Slavkovich, Vesna; Siddique, Abu B.; Alam, Shafiul; Islam, Tariqul; Graziano, Joseph H.; Gamble, Mary V.

In: Free Radical Biology and Medicine, Vol. 85, 12399, 16.06.2015, p. 174-182.

Research output: Contribution to journalArticle

Peters, Brandilyn A. ; Liu, Xinhua ; Hall, Megan N. ; Ilievski, Vesna ; Slavkovich, Vesna ; Siddique, Abu B. ; Alam, Shafiul ; Islam, Tariqul ; Graziano, Joseph H. ; Gamble, Mary V. / Arsenic exposure, inflammation, and renal function in Bangladeshi adults : effect modification by plasma glutathione redox potential. In: Free Radical Biology and Medicine. 2015 ; Vol. 85. pp. 174-182.
@article{4ea796460649488d854f4377e3baeb5b,
title = "Arsenic exposure, inflammation, and renal function in Bangladeshi adults: effect modification by plasma glutathione redox potential",
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.",
keywords = "Abbreviations AGP α-1 acid glycoprotein, bAs blood arsenic, 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, eGFR estimated glomerular filtration rate, FOX Folate and Oxidative Stress study, GFR glomerular filtration rate, GSH glutathione, GSSG glutathione disulfide, NF-κB nuclear factor κB, ROS reactive oxygen species, uAs urinary arsenic, uAs-SG urinary arsenic adjusted for specific gravity, wAs water arsenic.",
author = "Peters, {Brandilyn A.} and Xinhua Liu and Hall, {Megan N.} and Vesna Ilievski and Vesna Slavkovich and Siddique, {Abu B.} and Shafiul Alam and Tariqul Islam and Graziano, {Joseph H.} and Gamble, {Mary V.}",
year = "2015",
month = "6",
day = "16",
doi = "10.1016/j.freeradbiomed.2015.04.020",
language = "English (US)",
volume = "85",
pages = "174--182",
journal = "Free Radical Biology and Medicine",
issn = "0891-5849",
publisher = "Elsevier Inc.",

}

TY - JOUR

T1 - Arsenic exposure, inflammation, and renal function in Bangladeshi adults

T2 - effect modification by plasma glutathione redox potential

AU - Peters, Brandilyn A.

AU - Liu, Xinhua

AU - Hall, Megan N.

AU - Ilievski, Vesna

AU - Slavkovich, Vesna

AU - Siddique, Abu B.

AU - Alam, Shafiul

AU - Islam, Tariqul

AU - Graziano, Joseph H.

AU - Gamble, Mary V.

PY - 2015/6/16

Y1 - 2015/6/16

N2 - 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.

AB - 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.

KW - Abbreviations AGP α-1 acid glycoprotein

KW - bAs blood arsenic

KW - BMI body mass index

KW - CKD chronic kidney disease

KW - CRP C-reactive protein

KW - CVD cardiovascular disease

KW - EGSH reduction potential of the plasma GSSG/2GSH redox pair

KW - eGFR estimated glomerular filtration rate

KW - FOX Folate and Oxidative Stress study

KW - GFR glomerular filtration rate

KW - GSH glutathione

KW - GSSG glutathione disulfide

KW - NF-κB nuclear factor κB

KW - ROS reactive oxygen species

KW - uAs urinary arsenic

KW - uAs-SG urinary arsenic adjusted for specific gravity

KW - wAs water arsenic.

UR - http://www.scopus.com/inward/record.url?scp=84931272911&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84931272911&partnerID=8YFLogxK

U2 - 10.1016/j.freeradbiomed.2015.04.020

DO - 10.1016/j.freeradbiomed.2015.04.020

M3 - Article

C2 - 25916185

AN - SCOPUS:84931272911

VL - 85

SP - 174

EP - 182

JO - Free Radical Biology and Medicine

JF - Free Radical Biology and Medicine

SN - 0891-5849

M1 - 12399

ER -