Enhanced reactivity to malondialdehyde-modified proteins by systemic lupus erythematosus autoantibodies

R, Ben Mansour; Lassoued, Saloua; A, Elgaied; Haddouk, Samy; Marzouk, Samar; Bahloul, Z.; Masmoudi, Hatem; Attia, Hamadi; Ms, Aïfa; Fakhfakh, Feiza

doi:10.3109/03009740903362511

Cited by 56 publications

(61 citation statements)

References 56 publications

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“…After centrifugation at 3000 rpm for 15 min, the OD in the butanol phase was at 532 nm. Results are expressed in nmol/g of total protein [Ben Mansour et al 2010] Protein carbonyl groups. The protein-bound carbonyl concentration was measured as described previously [Flohe and Gunzler, 1984].…”

Section: Lipid Peroxidationmentioning

confidence: 99%

Lipid peroxidation, proteins modifications, anti-oxidant enzymes activities and selenium deficiency in the plasma of hashitoxicosis patients

Mseddi

Mansour

Mnif

et al. 2015

Therapeutic Advances in Endocrinology

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Objectives: The aim of this study was to explore the oxidative stress profile in hashitoxicosis (HTX) and to compare it with that of healthy subjects. Patients and methods: Spectrophotometric methods were used to evaluate the oxidative stress markers. The selenium level was investigated by atomic absorption. Results: High levels of thiobarbituric acid reactive species (TBARS) and conjugated dienes were found in HTX patients (p = 0.034 and p = 0.043, respectively) compared with healthy controls. For antioxidant enzymes, superoxide dismutase (SOD) and catalase activities increased, whereas that of glutathione peroxidase (GPx) decreased (p = 0.000, p = 0.014, p = 0.000, respectively) compared with controls. A reduction in the level of selenium (p = 0.029) and thiol groups (p = 0.008) were shown in patients; however, levels of carbonyl group and malondialdehyde (MDA) protein adducts decreased (p = 0.000) compared with controls. Positive correlation was shown between levels of free thyroxine (FT4) and TBARS (r = 0.711, p = 0.048) and between FT4 level and SOD activity (r = 0.713, p = 0.047). Conversely, GPx activity presented a negative correlation with FT4 and free triiodothyronine (FT3) levels (r = -0.934, p = 0.001; r = -0.993, p = 0.000, respectively). In addition, GPx activity showed positive correlation with selenium level (r = 0.981, p = 0.019) and the FT3 level correlated negatively with the level of thiol groups (r = -0.892, p = 0.017). Conclusions: This study shows the presence of an oxidative stress and selenium deficiency in HTX patients and suggests that the hyperthyroid state is strongly implicated in the establishment of this disturbed oxidative profile.

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Section: Lipid Peroxidationmentioning

confidence: 99%

Lipid peroxidation, proteins modifications, anti-oxidant enzymes activities and selenium deficiency in the plasma of hashitoxicosis patients

Mseddi

Mansour

Mnif

et al. 2015

Therapeutic Advances in Endocrinology

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“…Indeed, SLE is a disease characterized by an increased oxidative damage. [11][12][13][14] Free radical-mediated reactions are implicated in endothelial dysfunction in SLE, 15 and renal oxidative stress plays an important mechanistic role in the development of autoimmune-mediated hypertension.…”

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confidence: 99%

Chronic Hydroxychloroquine Improves Endothelial Dysfunction and Protects Kidney in a Mouse Model of Systemic Lupus Erythematosus

et al. 2014

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S ystemic lupus erythematosus (SLE) is a multisystemic chronic autoimmune inflammatory disorder that is associated with a high risk for the development of renal and cardiovascular disease, 1,2 which are major causes of mortality in these patients. 3 It predominantly affects young women of child-bearing age, the same population that is at lowest relative risk of atherosclerotic heart disease. In fact, women with lupus (age, 35-44 years) are >50 times as likely as healthy women without lupus to have a myocardial infarction. 4 Indeed, SLE is characterized by a high incidence of hypertension, 5-7 a wellestablished risk factor for the development and acceleration of atherosclerosis and ischemic heart disease. Oxidative stress and the inactivation of nitric oxide (NO) by vascular superoxide anion (O 2 ·− ) play a critical role in the pathogenesis of endothelial dysfunction, an early event in most cardiovascular diseases, including hypertension. 8,9 Reactive oxygen species (ROS) have been considered as risk and enhancer factors for autoimmune diseases, 10 and oxidation is one of the major factors responsible for atheroma development in this context. Indeed, SLE is a disease characterized by an increased oxidative damage.11-14 Free radical-mediated reactions are implicated in endothelial dysfunction in SLE, 15 and renal oxidative stress plays an important mechanistic role in the development of autoimmune-mediated hypertension. 16Abstract-Hydroxychloroquine has been shown to be efficacious in the treatment of autoimmune diseases, including systemic lupus erythematosus. Hydroxychloroquine-treated lupus patients showed a lower incidence of thromboembolic disease. Endothelial dysfunction, the earliest indicator of the development of cardiovascular disease, is present in lupus.Whether hydroxychloroquine improves endothelial function in lupus is not clear. The aim of this study was to analyze the effects of hydroxychloroquine on hypertension, endothelial dysfunction, and renal injury in a female mouse model of lupus. NZBWF1 (lupus) and NZW/LacJ (control) mice were treated with hydroxychloroquine 10 mg/kg per day by oral gavage, or with tempol and apocynin in the drinking water, for 5 weeks. Hydroxychloroquine treatment did not alter lupus disease activity (assessed by plasma double-stranded DNA autoantibodies) but prevented hypertension, cardiac and renal hypertrophy, proteinuria, and renal injury in lupus mice. Aortae from lupus mice showed reduced endotheliumdependent vasodilator responses to acetylcholine and enhanced contraction to phenylephrine, which were normalized by hydroxychloroquine or antioxidant treatments. No differences among all experimental groups were found in both the relaxant responses to acetylcholine and the contractile responses to phenylephrine in rings incubated with the nitric oxide synthase inhibitor N G -nitro-l-arginine methyl ester. Vascular reactive oxygen species content and mRNA levels of nicotinamide adenine dinucleotide phosphate oxidase subunits NOX-1 and p47 phox were increased in lupus...

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“…Oxidative stress with an increase in malondialdehyde (MDA) and a decrease in antioxidant thiols plays a strong role in the progression of SLE disease [6]. Inhibition of oxidative stress may represent newly discovered molecular and cellular targets for the treatment of SLE [1].…”

Section: Introductionmentioning

confidence: 99%

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

Gheita

Kenawy

2014

Methods in Molecular Biology

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Oxidative stress contributes to chronic inflammation of tissues and plays a central role in immunomodulation, which may lead to autoimmune diseases such as systemic lupus erythematosus (SLE) and antiphospholipid syndrome. Markers of oxidative damage include malondialdehyde (MDA), antioxidant scavengers as glutathione (GSH), and glutathione peroxidase (GSH Px), which all correlate well with SLE disease activity. Amelioration of some clinical manifestations of SLE may be expected by targeting lipid peroxidation with dietary or pharmacological antioxidants. Here, we describe the detection of the key players of oxidant/antioxidant imbalance in SLE.

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Enhanced reactivity to malondialdehyde-modified proteins by systemic lupus erythematosus autoantibodies

Abstract: These data reinforce the role of oxidative stress and especially lipid peroxidation products in the progression of SLE disease.

Cited by 56 publications

References 56 publications

Lipid peroxidation, proteins modifications, anti-oxidant enzymes activities and selenium deficiency in the plasma of hashitoxicosis patients

Lipid peroxidation, proteins modifications, anti-oxidant enzymes activities and selenium deficiency in the plasma of hashitoxicosis patients

Chronic Hydroxychloroquine Improves Endothelial Dysfunction and Protects Kidney in a Mouse Model of Systemic Lupus Erythematosus

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

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