Oxidative and Nitrosative Stress in Trichloroethene-Mediated Autoimmune Response
Posted Sep 11 2009 4:57pm
Autoimmune diseases such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA) and scleroderma are chronic and life-threatening disorders that affect ~3% of United States population, and are among the leading causes of death for women under the age of 65.
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.
In conclusion, this studies demonstrate that long-term, low dose Trichloroethene(TCE) exposure leads to both oxidative and nitrosative stress and induction/exacerbation of autoimmune response. Increased formation of LPDAs such as MDA and HNE, leading to the formation of neoantigens, may elicit autoimmune responses by stimulating T and B lymphocytes.
Further, persistent increases in antibodies to LPDA-protein adducts may lead to formation of immune complexes whose deposition in tissues could be a pathogenic mechanism of autoimmune diseases. The proposed sequence of events leading to autoimmune response.
However, extensive interventional studies are needed to establish the causal role of RONS in TCE-mediated autoimmunity. Establishing the role of oxidative/nitrosative stress in autoimmune diseases through exposure to such chemicals as TCE, could be a step forward toward attributing the role of environmental chemicals in autoimmune diseases.
The anticipated sequence of events leading to autoimmune diseases following trichloroethene-induced oxidative stress.