Markers of oxidative and nitrosative stress in systemic lupus erythematosus: Correlation with disease activity

Abstract

Objective. Free radical-mediated reactions have been implicated as contributors in a number of autoimmune diseases, including systemic lupus erythematosus (SLE). However, the potential for oxidative/ nitrosative stress to elicit an autoimmune response or to contribute to disease pathogenesis, and thus be useful when determining a prognosis, remains largely unexplored in humans. This study was undertaken to investigate the status and contribution of oxidative/ nitrosative stress in patients with SLE.Methods. Sera from 72 SLE patients with varying levels of disease activity according to the SLE Disease Activity Index (SLEDAI) and 36 age-and sex-matched healthy controls were evaluated for serum levels of oxidative/nitrosative stress markers, including antibodies to malondialdehyde (anti-MDA) protein adducts and to 4-hydroxynonenal (anti-HNE) protein adducts, MDA/HNE protein adducts, superoxide dismutase (SOD), nitrotyrosine (NT), and inducible nitric oxide synthase (iNOS).Results. Serum analysis showed significantly higher levels of both anti-MDA/anti-HNE protein adduct antibodies and MDA/HNE protein adducts in SLE patients compared with healthy controls. Interestingly, not only was there an increased number of subjects positive for anti-MDA or anti-HNE antibodies, but also the levels of both of these antibodies were statistically significantly higher among SLE patients whose SLEDAI scores were >6 as compared with SLE patients with lower SLEDAI scores (SLEDAI score <6). In addition, a significant correlation was observed between the levels of anti-MDA or anti-HNE antibodies and the SLEDAI score (r ‫؍‬ 0.734 and r ‫؍‬ 0.647, respectively), suggesting a possible causal relationship between these antibodies and SLE. Furthermore, sera from SLE patients had lower levels of SOD and higher levels of iNOS and NT compared with healthy control sera.Conclusion. These findings support an association between oxidative/nitrosative stress and SLE. The stronger response observed in serum samples from patients with higher SLEDAI scores suggests that markers of oxidative/nitrosative stress may be useful in evaluating the progression of SLE and in elucidating the mechanisms of disease pathogenesis.

Malondialdeído e grupo sulfidrila como biomarcadores do estresse oxidativo em pacientes com lúpus eritematoso sistêmico

“…Increased level of MDA in the serum 18 and in the erythrocytes 19 was reported in SLE patients. Wang et al 20 and Shah et al 21 associated stronger oxidative stress response with higher SLEDAI scores, similar to the previous report of Tewthanom et al 18 However, we have not identifi ed, in our study, the association of MDA or SH levels with SLEDAI scores. The high levels of MDA in SLE patients indicate that the lipid cell membrane was attacked and that MDA can be a good marker of oxidative stress in this disease.…”

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

“…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.…”

“…Increasing evidence suggests that ROS-modified proteins such as protein carbonyls and lipid peroxidation-derived aldehydes [LPDAs, including malondialdehyde (MDA) and 4-hydroxynonenal (HNE)]-protein adducts may elicit an autoimmune response and contribute to disease pathogenesis (Ben Mansour et al, 2010). Indeed, higher levels of MDA-/HNE-modified proteins and protein carbonyls have been seen in autoimmune disease patients (Ben Mansour et al, 2010;Wang et al, 2010), illustrating a role for these oxidative modified proteins in autoimmune diseases. Oxidative stress can affect cell integrity only when antioxidant mechanisms are no longer able to cope with free radical generation.…”

Measurement of Malondialdehyde, Glutathione, and Glutathione Peroxidase in SLE Patients

“…Reactive oxygen species (ROS) have been considered as risk and enhancer factors for autoimmune diseases [4], and free radical-mediated reactions are implicated in SLE. Oxidative stress has a potential to elicit an autoimmune response and to contribute to the disease pathogenesis thus being useful when determining its prognosis [5]. Alopecia and lupus nephritis are remarkably associated with oxidative stress and impaired antioxidant systems in SLE patients [4].…”