Abstract
Background:
Vascular endothelial dysfunction is a central event in pathogenesis of a variety of human diseases. Systemic sclerosis is one of such diseases. The oxidative stress and depletion of antioxidants in the serum is believed to be one of the factors in causing this dysfunction.
Aims:
The aim of this case control study was to compare the levels of antioxidants in the serum of patients with systemic sclerosis and the normal age and sex matched controls.
Materials and Methods:
Our study consisted of 16 successively admitted patients with systemic sclerosis and 16 healthy, age and sex matched controls. The age group of patient's ranged between 25 and 55 years. The duration of the disease in patients ranged from 1 to 8 years. The serum of patients and controls were assayed for the levels of antioxidants (GSH, NO, MDA, SOD and GPX) by spectrophotometry. The statistical method of analysis used was the one sample t-test.
Results:
The median levels of antioxidants in the control patients were: SOD-4.14 units/ml; GSH-4.76 units/ml; NO-5.58 nmol/l; MDA-0.53 nmol/l and GPX-49 μmol/l. The levels of NO, GSH and SOD were decreased in these patients with a significant P value (<0.001) whereas the levels of GPX and MDA were normal to increased with a significant P value.
Conclusion:
The depletion of antioxidants and oxidative stress in serum might be responsible for the vascular dysfunction and other hallmark manifestations of systemic sclerosis. Therefore micronutrient antioxidant supplements may be of therapeutic value.
Keywords: Glutathione peroxidase, glutathione, malondialdehyde, nitric oxide, superoxide dismutase
Introduction
What was known?
Oxidant-antioxidant imbalance is postulated as one of the pathogenic mechanisms in systemic sclerosis.
Scleroderma is a connective tissue disease that involves changes in skin, blood vessels, muscles and internal organs. It is a type of autoimmune disorder, a condition that occurs when immune system mistakenly attacks and destroys the body tissues. The cause is not known.[1] Various etiological factors have been postulated like genetic, environmental, immune mediated, infective and toxic etc., There are 3 main hallmarks of system sclerosis:
Cellular and humoral immunity activation
Microvascular damage and
Widespread tissue fibrosis.[2]
Many lines of independent research have pointed out the role of oxidative stress as a fascinating pathogenic link between 3 main hallmarks of systemic sclerosis.[3] In this study the levels of antioxidants were assayed in the serum of patients with systemic sclerosis, and compared with the levels in healthy age and sex matched controls.
Materials and Methods
The study consisted of 16 patients with systemic sclerosis (3 limited and 13 diffuse cutaneous systemic sclerosis) who attended the outpatient department of Dermatology STD and Leprosy, GMC, Srinagar. All the patients were females with age group ranging between 25 and 55 years. The disease duration ranged from 1 to 8 years. A complete history with a detailed physical examination was done in each patient including a modified Rodnan's scoring system for skin thickness (which ranged from 3 to 11 in these patients). A total of 5 ml of the patients blood sample were taken, which was centrifuged to isolate the serum in the Department of Biochemistry, GMC Srinagar, in which the levels of antioxidants (NO, GSH, MDA, SOD and GPX) were assayed by spectrophotometry. Informed consent was obtained from each patient. The study was approved by the local ethical committee.
Results
The median levels of antioxidants in the controls were SOD-4.14 units/ml, GSH-4.76 units/ml, MDA-0.53 nmol/l, GPX-49 μmol/l and NO-5.58 nmol/ml. The serum levels of NO, GSH and SOD were decreased in the patients with a significant P value while as the levels of GPX and MDA were increased with a significant P value.
Statistical analysis
It was done by one sample t-test (two-tailed); significance was set at P < 0.05.
Discussion
Systemic sclerosis is a connective tissue disease that involves changes in skin, blood vessels, muscles and internal organs. It is a type of autoimmune disorder, a condition that occurs when the immune system mistakenly attacks and destroys the healthy body tissues. The cause is not known. Various etiological theories that have been postulated include genetic, environmental, immune-mediated, infective and toxic etc.,[1] It usually affects people in the age group of 30-50 years with the M:F ratio of 3-4:1. It can occur with the connective tissue disease like lupus erythematosus, dermatomyositis and polymyositis when it is called mixed connective tissue disease.[3,4] It is of 2 types: Localized or limited cutaneous sclerosis and diffuse systemic sclerosis.[5,6]
There are a number of diseases where oxidative stress and depletion of antioxidant defense mechanisms are a prominent feature, examples include: Systemic sclerosis, hepatic cirrhosis, pre-eclampsia, pancreatitis, rheumatoid arthritis, mitochondrial diseases, neonatal oxidative stress and dialysis.[7]
An oxidant-antioxidant imbalance has been suggested as another etiopathogenic mechanism in systemic sclerosis, especially in the development of pulmonary fibrosis and drugs with antioxidant effects have been tested in systemic sclerosis e.g., Pirfenidone, an anti-inflammatory drug that has antioxidant and antifibrotic effects improved the vital capacity and prevented acute exacerbations of idiopathic interstitial lung disease (2005, a randomized controlled study). N-acetylcysteine, a precursor of GSH has shown a lower rate of worsening in pulmonary function in a randomized controlled study.[8] Many lines of independent research have pointed out the role of oxidative stress as a fascinating pathogenic link between the 3 main hallmarks of systemic sclerosis, viz. cellular and humoral immunity activation, microvascular damage and widespread tissue fibrosis.[9,10]
Conclusion
The deficiency of antioxidants in the serum of patients with systemic sclerosis may predispose them toward the irreversible tissue injury and since our study has shown the decreased levels of antioxidants (NO, GSH and SOD with a significant P value), the micronutrient antioxidant supplements may be of therapeutic value in these patients.
What is new?
Modulation of fibrosis in systemic sclerosis by NO and antioxidants, however large case studies are needed.
Acknowledgment
Dr. Sabiya Majid, Department of Biochemistry, GMC, Srinagar.
Footnotes
Source of Support: Nil
Conflict of Interest: Nil.
References
- 1.Mayes MD. Classification and epidemiology of scleroderma. Semin Cutan Med Surg. 1998;17:22–6. doi: 10.1016/s1085-5629(98)80058-8. [DOI] [PubMed] [Google Scholar]
- 2.Haustein UF. Systemic sclerosis-scleroderma. Dermatol Online J. 2002;81:3. [PubMed] [Google Scholar]
- 3.Herric AL. Vascular function in systemic sclerosis. Curr Opin Rheumatol. 2000;12:527. doi: 10.1097/00002281-200011000-00009. [DOI] [PubMed] [Google Scholar]
- 4.Herric AL, Rieley F, Schofield D. Micronutrient antioxidant status in patients with primary Raynaud's phenomenon and systemic sclerosis. J Rheumatol. 1994;21:1477–83. [PubMed] [Google Scholar]
- 5.Musellim B, Iktimur H, Uzun H, Ongen G. The oxidant antioxidant balance in systemic sclerosis cases with interstitial lung involvement. Rheumatol Int. 2006;27:163–7. doi: 10.1007/s00296-006-0184-6. [DOI] [PubMed] [Google Scholar]
- 6.Erre GL, Passiu G. Antioxidant effect of iloprost: Current knowledge and therapeutic implications for systemic sclerosis. Rheumatismo. 2009;61:90–7. doi: 10.4081/reumatismo.2009.90. [DOI] [PubMed] [Google Scholar]
- 7.Herric AL, Worthington H, Rieley F. Dietary intake of micronutrient antioxidants in relation to blood levels in patients with systemic sclerosis. J Rheumatol. 1996;23:650–3. [PubMed] [Google Scholar]
- 8.Horrobin DF. Essential fatty metabolism in diseases of connective tissue with special reference to scleroderma and sjogren's syndrome. Med Hypotheses. 1984;14:233–47. doi: 10.1016/0306-9877(87)90123-x. [DOI] [PubMed] [Google Scholar]
- 9.Nelson JL. Microchimerism and the pathogenesis of systemic sclerosis. Curr Opin Rheumatol. 1998;10:564–71. doi: 10.1097/00002281-199811000-00010. [DOI] [PubMed] [Google Scholar]
- 10.Mayes MD, Lacey JV, Jr, Beebe-Dimmer J, Gillespie BW, Cooper B, Laing TJ, et al. Prevalance, incidence, survival and disease characteristics of systemic sclerosis in a large US population. Arthritis Rheum. 2003;48:2246–55. doi: 10.1002/art.11073. [DOI] [PubMed] [Google Scholar]