Oxidative and nitrosative stress in trichloroethene-mediated autoimmune response

Abstract

Reactive oxygen and nitrogen species (RONS) are implicated in the pathogenesis of several autoimmune diseases. Also, increased lipid peroxidation and protein nitration are reported in systemic autoimmune diseases. Lipid peroxidation-derived aldehydes (LPDAs) such as malondialdehyde (MDA) and 4-hydroxynonenal (HNE) are highly reactive and bind proteins covalently, but their potential to elicit an autoimmune response and contribution to disease pathogenesis remain unclear. Similarly, nitration of protein could also contribute to disease pathogenesis. To assess the status of lipid peroxidation and/or RONS, autoimmune-prone female MRL +/+ mice (5-week old) were treated with trichloroethene (TCE), an environmental contaminant known to induce autoimmune response, for 48 weeks (0.5 mg/ml via drinking water), and formation of antibodies to LPDA-protein adducts was followed in the sera of control and TCE-treated mice. TCE treatment led to greater formation of both anti-MDA-and and-HNE-protein adduct antibodies and higher serum iNOS and nitrotyrosine levels. The increase in TCE-induced oxidative stress was associated with increases in anti-nuclear-, anti-ssDNA-and anti-dsDNA-antibodies. These findings suggest that TCE exposure not only leads to oxidative/nitrosative stress, but is also associated with induction/exacerbation of autoimmune response in MRL +/+ mice. Further interventional studies are needed to establish a causal role of RONS in TCE-mediated autoimmunity.

Cellular and molecular etiology of hepatocyte injury in a murine model of environmentally induced liver abnormality

“…4b). Discussion The exposure to environmental toxic chemicals can cause several detrimental effects in biological cell systems (Topham, 1980;House et al, 1996;Snyder and Andrews, 1996;Griffin et al, 2000;Wang et al, 2007Wang et al, , 2013Al-Griw et al, 2015a,b,c). TCE, a widely used industrial agent and a ubiquitous environmental contaminant, is non-carcinogenic (group 3) because there is inadequate evidence for carcinogenicity in both human and animals according to EPA and National Toxicology Program (NTP) technical report (NTP, 2000;EPA, 2007).…”

“…However, the Agency for Toxic Substances and Disease Registry (ATSDR) indicated that TCE affects many internal organs and systems such as cardiovascular and nervous system (Lawrence, 2006). TCE has been implicated in the development of autoimmune disorders in humans (Cooper et al, 2009) and induces autoimmune response in experimental animals (Wang et al, 2007(Wang et al, , 2013Cooper et al, 2009). However, the mechanisms by which TCE induces/accelerates the autoimmune disease pathogenesis are still unclear.…”

“…In recent years, free radical-mediated reactions as the potential mechanism in the pathogenesis of autoimmune diseases have drawn increasing attention (Khan et al, 2001). TCE is known to generate free radicals, and cause increased lipid peroxidation in both in vivo and in vitro models (Khan et al, 2001;Wang et al, 2007). Several lines of evidence in lupus-prone mice showed that increased generation of ROS was correlated with increased autoantibodies production, illustrating a potential role of oxidative stress in TCE induced autoimmune response (Wang et al, 2007(Wang et al, , 2010.…”

“…TCE is known to generate free radicals, and cause increased lipid peroxidation in both in vivo and in vitro models (Khan et al, 2001;Wang et al, 2007). Several lines of evidence in lupus-prone mice showed that increased generation of ROS was correlated with increased autoantibodies production, illustrating a potential role of oxidative stress in TCE induced autoimmune response (Wang et al, 2007(Wang et al, , 2010. Although there is a large body of literature addressing immune responses during environmental chemicals exposure, the TCE immunotoxicity is poorly understood.…”

“…Although there is a large body of literature addressing immune responses during environmental chemicals exposure, the TCE immunotoxicity is poorly understood. Even though TCE is known to generate free radicals, causes increased oxidative stress and induces autoimmune response (Wang et al, 2007(Wang et al, , 2013, potential mechanisms by which TCE induced ROS generation lead to an autoimmune response and their contribution to disease pathogenesis remains largely unknown.…”