The Effect of Oxidative Stress on Pulmonary Involvement in Patients with Systemic Sclerosis

Systemic sclerosis (SSc) is a connective tissue disease characterized by fibrosis of the skin, blood vessels, skeletal muscles, and visceral organs and associated with some immunological abnormalities and vascular injury. Collagen overproduction by activated stromal fibroblasts, autoantibody production and acral vasospasm known as Raynaud’s phenomenon are the hallmarks of the disease. There are two major subgroups: limited cutaneous SSc and diffuse cutaneous SSc. The kidneys, esophagus, heart, and lungs are the most frequent targets.

Under normal circumstances there is a balance between oxidant agents and antioxidant defense mechanisms, and if this balance is disturbed oxidative stress occurs. Reactive oxygen species (ROS) such as superoxide anion radicals (O2−) are known as oxidant agents. Malondialdehyde (MDA) as a lipid peroxidation end product is an indicator of oxidative stress Xanthine oxidase (XO) is an oxidant enzyme catalyzing oxidation of hypoxanthine to xanthine and xanthine to uric acid, and can produce O2− during these reactions. Superoxide dismutase (SOD) catalyzes the dismutation of O2− to hydrogen peroxide (H2O2), and catalase (CAT) and glutathione peroxidase (GSH-Px) are the enzymes that catalyze the reduction of H2O2 to water. SOD, CAT, and GSH-Px are known as endogenous antioxidant enzymes playing important role in antioxidant defense. Adenosine deaminase is a key enzyme in the degradation of adenine nucleotide .

Free radical mediated damage could be an important basis for the SSc pathogenesis. Oxidative stress is supposed to play a role on endothelial injury at earlier stages of the disease. Modifications of the vascular system leads to loss of the control of vascular tone. The oxygen free radical species can be generated during Raynaud’s phenomenon that causes hypoxic/ischemic episodes, with consequent lipid peroxidation and tissue damage. Free radicals are harmfull to cells, modifying cellular macromolecules including lipids, proteins, carbohydrates and nucleic acids. Variation in prooxidant or antioxidant genes may also be associated with SSc .

There is evidence of an association between oxidative stress and SSc from several studies. Lipid peroxidation products, which are markers of oxidative stress were found at highest levels in patients with interstitial lung disease and in patients with frequent ischemia/ reperfusion episodes. Inflammation can play a predominant role in the generation of reactive oxygen species. Tissue damage by respiratory burst of polymorphonuclear leucocytes can occur especially in lungs. The oxygen free radicals are supposed to contribute to the tissue damage occuring in diffuse lung diseases, a heterogenous group of diseases with pulmonary fibrosis of various degrees of severity. Pulmonary involvement (interstitial lung disease and pulmonary hypertension) and cardiac involvement are major causes of death in SSc. Therefore, the aim of this study was to to measure levels of oxidant and antioxidant enzymes in patients with Ssc, to evaluate possible contibution of oxidative stress to the pathogenesis of SSc and pulmonary involvement and its severity.