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

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 m(2) (p = 0.08), respectively. In stratified analyses, the effect of As exposure on CRP was observed only in participants having EhGSH > median (uAs p(Wald) = 0.03; bAs p(Wald) = 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: Arsenic; Bangladesh; C-reactive protein; Cystatin C; Free radicals; Glomerular filtration rate; Glutathione; Inflammation; Kidney; Oxidative stress; Redox; α-1 acid glycoprotein.