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 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.

Catechin Attenuates the Effect of Combined Arsenic and Deltamethrin Toxicity by Abrogation of Oxidative Stress and Inflammation in Wistar Rats

“…The elevated IL-6 and TNF-α levels observed could thus, be a result of these redox-sensitive factors, activated by combined As and DM induced oxidative stress. Several studies have shown that either toxicant can induce the expression of proinflammatory cytokines [7,47]. 8-NO 2 -Gua is a product of the interaction of the highly reactive peroxynitrite, formed when nitric oxide synthase reacts with superoxide, and guanine, during inflammation [48].…”

“…Exposure to arsenic (As) has been associated with a wide range of toxic effects [5,6]. These toxic effects include cancer of various types, diabetes mellitus, hepatomegaly, cerebrovascular and cardiovascular diseases among many others [7]. Arsenic generally exerts its toxicity through the generation of reactive oxygen species and the disruption of cellular antioxidant defense system [8].…”

Effect of Curcumin and N-Acetylcysteine on Brain Histology and Inflammatory Factors (MMP-2, 9 and TNF-α) in Rats Exposed to Arsenic

“…30 A growing number of studies have shown that chronic exposure to arsenic enhances inflammatory responses and subsequently oxidative stress by generating ROS. [31][32][33][34] For example, maternal exposure to arsenic has been reported to be associated with increased placental contents of inflammatory markers such as 8-oxoguanine (8-oxoG), interleukin-1β (IL-1β), TNF-α and interferon-gamma (IFN-γ). 35 In another study, arsenic exposure was associated with increased renal inflammation and decreased estimated glomerular filtration rate.…”

“…35 In another study, arsenic exposure was associated with increased renal inflammation and decreased estimated glomerular filtration rate. 34 Ma et al, 36 illustrated that arsenic results in oxidative stress and inflammation through induction of NADPH oxidase (NOX) activity and overproduction of nitric oxide (NO). A more recent study has reported that chronic exposure to arsenic is associated with lung inflammation and impaired lung function.…”

Arsenic Trioxide Attenuates NF-κB and Cytokine mRNA Levels in the Livers of Cocks

“…3). As exposure can affect inflammation and renal function as shown in Bangladeshi adults [17]. We therefore examined the effect on hepatic immune function by measuring the mRNA levels of hepatic cytokines.…”