N-Acetylcysteine protects against trichloroethene-mediated autoimmunity by attenuating oxidative stress

Abstract

Exposure to trichloroethene (TCE), a ubiquitous environmental contaminant, is known to induce autoimmunity both in humans and animal models. However, mechanisms underlying TCE-mediated autoimmunity remain largely unknown. Previous studies from our laboratory in MRL+/+ mice suggest that oxidative stress may contribute to TCE-induced autoimmune response. The current study was undertaken to further assess the role of oxidative stress in TCE-induced autoimmunity by supplementing with an antioxidant N-acetylcysteine (NAC). Groups of female MRL+/+ mice were given TCE, NAC or TCE + NAC for 6 weeks (TCE, 10 mmol/kg, i.p., every 4th day; NAC, 250 mg/kg/day through drinking water). TCE exposure led to significant increases in serum levels of anti-nuclear, anti-dsDNA and anti-Sm antibodies. TCE exposure also led to significant induction of anti-malondiadelhyde (MDA)- and anti-hydroxynonenal (HNE)-protein adduct antibodies which were associated with increased ANA in the sera along with increased MDA-/HNE-protein adducts in the livers and kidneys, and increases in protein oxidation (carbonylation) in the sera, livers and kidneys, suggesting an overall increase in oxidative stress. Moreover, TCE exposure also resulted in increased release of IL-17 from splenocytes and increases in IL-17 mRNA expression. Remarkably, NAC supplementation attenuated not only the TCE-induced oxidative stress, IL-17 release and mRNA expression, but also the markers of autoimmunity, as evident from decreased levels of ANA, anti-dsDNA and anti-Sm antibodies in the sera. These results provide further support to a role of oxidative stress in TCE-induced autoimmune response. Attenuation of TCE-induced autoimmunity in mice by NAC provides an approach for preventive and/or therapeutic strategies.

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

“…Various concentrations of TCE (Baxter International) were dissolved in corn oil and administered to mice intraperitoneally with repeated doses (100 or 400 µg/kg BW TCE twice weekly for three weeks). The doses were calculated and delivered in 80-100 µl of corn oil based on their body weight (Melani et al, 2003;Wang et al, 2013). TCE doses were selected as they considered safe by Environmental Protection Agency (EPA) (Lane et al, 1982).…”

“…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).…”

“…One of the most concerned issues in the modern society is evaluating the toxicity of environmental (pollutant) chemicals, such as cadmium, mercury, bisphenol A (BPA), dioxin and trichloroethane (TCE). Some of these toxicants show immediate effect whereas others can result in subtle alterations that are delayed in their expression (Wang et al, 2013). TCE is considered as ubiquitous environmental toxicant and it is a volatile organic solvent that has been used in large quantities as an industrial dissolvent, a metal degreaser, a chemical intermediate, and as a component of consumer products (Warren et al, 1998;Wang et al, 2013).…”

“…Some of these toxicants show immediate effect whereas others can result in subtle alterations that are delayed in their expression (Wang et al, 2013). TCE is considered as ubiquitous environmental toxicant and it is a volatile organic solvent that has been used in large quantities as an industrial dissolvent, a metal degreaser, a chemical intermediate, and as a component of consumer products (Warren et al, 1998;Wang et al, 2013). TCE has been originally produced as a safer alternative to other chlorinated solvents; as its acute and chronic toxicities are relatively low (EPA, 2007).…”

“…Al-Griw et al Open Veterinary Journal, (2016), Vol. 6(3): 150-157 reported in various diseases (Khan et al, 2001;Morgan et al, 2005;Oates, 2010;Wang et al, 2013). Proteins perform crucial functions within living cells, but even a relatively minor structural modification of proteins often leads to a marked change (generally lowering) in their functions (Orengo et al, 1999).…”