Protective Effects of Alpha-Lipoic Acid Against Oxidative Injury in TNBS-induced Colitis
1Department of Pharmacology Marmara University Farmacy Faculty, İstanbul,Turkey
2Health Services Vocational College Marmara University, İstanbul,Turkey
3Department of Embriology & Histology Marmara University Medical Faculty, İstanbul,Turkey
4Department of Medical Biology Marmara University Medical Faculty, İstanbul,Turkey
5Department of Physiology Marmara University Medical Faculty, İstanbul,Turkey
J Clin Pract Res 2009; 31(1): 15-26
Full Text PDF

Abstract

Purpose: Alpha-Lipoic acid (ALA), which has been intensely investigated as a therapeutic agent for several diseases, is elucidated for its possible protective effect as a potent antioxidant on colonic inflammation.
Materials and Methods: Following intracolonic administration of trinitrobenzene sulphonic acid, Sprague-Dawley rats were treated orally either with saline or ALA (100 mg/kg/day), for three days. On the 4th day, rats were decapitated and distal colon was removed for the macroscopic and microscopic damage scoring, for the measurement of malondialdehyde (MDA), glutathione (GSH) and collagen levels, myeloperoxidase (MPO) and Na+- K+-ATPase activity, luminol and lucigenin chemiluminescences (CL) and oxidant-induced DNA fragmentation. Lactate deydrogenase (LDH) activity, TNF- α, IL-1β, IL-6 and antioxidant capacity (AOC) were assayed in blood samples.
Results: Colitis caused significant increases in the colonic macroscopic and microscopic damage scores, MDA, and collagen levels, MPO activity and CL values, along with a significant decrease in tissue GSH level and Na+- K+-ATP ase activity. Similarly, serum cytokines as well as LDH were elevated in the vehicle-treated colitis group as compared to control group. On the other hand, ALA treatment reversed all these biochemical indices, as well as histopathological alterations induced by TNBS.
Conclusion: ALA protects the colonic tissue via its antioxidant and membrane stabilizing properties.


TNBS ile Oluşturulan Kolitte Alfa Lipoik Asitin Oksidatif Hasara Karşı Koruyucu Etkileri
1Department of Pharmacology Marmara University Farmacy Faculty, İstanbul,Turkey
2Health Services Vocational College Marmara University, İstanbul,Turkey
3Department of Embriology & Histology Marmara University Medical Faculty, İstanbul,Turkey
4Department of Medical Biology Marmara University Medical Faculty, İstanbul,Turkey
5Department of Physiology Marmara University Medical Faculty, İstanbul,Turkey
Journal of Clinical Practice and Research 2009; 1(31): 15-26

Amaç: Alfa-Lipoik asit (ALA), birçok hastalıkta terapötik ajan olarak incelenmektedir. Bu çalışmada potent bir antioksidan olan ALA'nın kolonik inflamasyonda olası protektif etkisinin incelenmesi amaçlanmıştır.
Gereç ve Yöntemler: Sprague-Dawley sıçanlara intrakolonik trinitrobenzeno sülfonik asit (TNBS), uygulamasını takiben 3 gün süreyle oral olarak serum fizyolojik ya da ALA (100 mg/kg/gün) verildi. 4. gün sonunda sıçanlar dekapite edilerek kan ve doku örnekleri alındı. Distal kolonda makroskopik ve mikroskopik hasar skorlaması yapıldı Ayrıca dokuda malondialdeit (MDA), glutatyon (GSH) ve kollagen düzeyleri ile myeloperoksidaz (MPO) ve Na+- K+-ATPase aktiviteleri ve luminol ve lusigenin kemiluminesans (CL) düzeyleri ve oksidan-aracılı DNA fragmentasyonu ölçüldü. Kan örneklerinde Laktat dehidrogenaz (LDH) aktivitesi, TNF- α, IL- 1β, IL-6 ve antioksidan kapasite (AOC) düzeyleri değerlendirildi.
Bulgular: Kolit kolonik makroskopik ve mikroskopik hasar skorlarında, MDA ve kollagen düzeylerinde, MPO aktivitesinde anlamlı artışa, GSH düzeylerinde ve Na+- K+-ATP az aktivitesinde ise anlamlı olarak azalmaya neden olmaktadır. Benzer olarak kolit gruplarında serum sitokinlerinin ve LDH düzeylerinin anlamlı olarak yüksek bulunduğu görülmüştür. ALA uygulaması TNBS ile görülen biyokimyasal ve histopatolojik değişiklikleri anlamlı olarak düzeltmektedir.
Sonuç: ALA'nın antioksidan ve membrane stabilize edici etkilerinden dolayı kolon dokusunda koruyucu etki gösterdiği düşünülmektedir.