Title: N-Acetylcysteine protects against trichloroethene-mediated autoimmunity by attenuating oxidative stress.
Authors: Wang, Gangduo; Wang, Jianling; Ma, Huaxian; Ansari, G A S; Khan, M Firoze
Published In Toxicol Appl Pharmacol, (2013 Nov 15)
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, 10mmol/kg, i.p., every 4th day; NAC, 250mg/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.
PubMed ID: 23993974
MeSH Terms: Acetylcysteine/pharmacology*; Animals; Antibodies, Antinuclear/blood; Autoantibodies/blood; Autoimmune Diseases/chemically induced; Autoimmune Diseases/drug therapy*; Female; Interleukin-17/genetics; Interleukin-17/metabolism; Kidney/drug effects; Kidney/metabolism; Lipid Peroxidation/drug effects; Liver/drug effects; Liver/metabolism; Mice; Mice, Inbred MRL lpr; Oxidative Stress/drug effects*; Protein Carbonylation/drug effects; RNA, Messenger/genetics; RNA, Messenger/metabolism; Spleen/cytology; Spleen/drug effects; Spleen/metabolism; Trichloroethylene/toxicity*