Effect of Alpha Lipoic Acid Treatment on SOD and NLRP3 Levels in Experimental Rat Colitis Model

Year 2025, Volume: 5 Issue: 1, 38 - 48, 17.03.2025

Gülbeyaz Özkan , Derya Demir , İrem Taner , Nur Banu Bal , Mürşide Demirel

https://doi.org/10.62425/jlasp.1565052

Abstract

Ulcerative colitis is a disease accompanied by chronic inflammation of the mucosa and submucosa layers of the colon. Colon inflammation causes the release of reactive oxygen and nitrogen derivatives due to excessive activation of immune system cells, and oxidative stress. In our study, the serum and colon NOD-like receptor protein 3 (NLRP3) levels and colon superoxide dismutase (SOD) levels were investigated in the acetic acid-induced colitis model in rats. Furthermore, this study aims to investigate the regulatory effects of alpha-lipoic acid, a potent antioxidant, on these parameters. In our study, 34 healthy 8-10 week-old male Wistar Albino rats weighing 200-250 g were used. The animals were divided into 5 groups with 6 in the control group and 7 in each study group. To induce colitis, 4% acetic acid was administered intrarectally to the animals, except for the control group. Subsequently, treatment was initiated with alpha-lipoic acid, mesalamine, and a combination of both, continuing for 14 days. Diarrhea scores of the animals were recorded throughout the treatment procedure. After the experiment, serum and colon tissue NLRP3, as well as SOD levels in the colon were evaluated. The diarrhea score was observed to significantly increase in the colitis group compared to the other groups, while it significantly decreased in the mesalamine+alpha-lipoic acid group. In the colitis group, NLRP3 levels in the serum and colon tissue were the highest, while colon SOD levels were the lowest. These parameters were significantly regulated in the mesalamine+alpha lipoic acid group compared to the other groups. In conclusion, it was determined that NLRP3 inflammasome activity increases and SOD levels decrease in cases of colitis; moreover, the combination of alpha-lipoic acid with mesalamine had a more pronounced regulatory effect on these values compared to their use alone.

Keywords

Alpha lipoic acid, diarrhea, colitis, inflammation, oxidation

Deneysel Sıçan Kolit Modelinde Alfa Lipoik Asit Tedavisinin SOD ve NLRP3 Seviyesi Üzerine Etkisi

Abstract

Ülseratif kolit, kolonun mukozal ve submukozal tabakalarının kronik inflamasyonuyla seyreden bir hastalıktır. Kolon inflamasyonu, immün sistem hücrelerinin aşırı aktivasyonuna yol açarak reaktif oksijen ve nitrojen türevlerinin salınmasına ve oksidatif strese sebep olmaktadır. Çalışmamızda, ratlarda asetik asitle oluşturulmuş kolit modelinin serum ve kolon dokusu NOD benzeri reseptör proteini 3 (NLRP3) ile kolon süperoksit dismutaz (SOD) düzeyleri üzerine etkileri araştırılmıştır. Ayrıca, güçlü bir antioksidan olan alfa lipoik asitin bu parametreler üzerine düzenleyici etkilerinin araştırılması da amaçlanmıştır. Araştırmamızda, 8-10 haftalık 200-250 g ağırlığında sağlıklı 34 adet erkek Wistar Albino ırkı sıçan kullanıldı. Hayvanlar kontrol grubunda 6, deney gruplarında 7 hayvan olacak şekilde 5 gruba ayrıldı. Kontrol grubu dışındaki hayvanlara kolit indüksiyonu amacıyla %4 asetik asit intrarektal olarak uygulandı. Daha sonra alfa lipoik asit, mesalamin ve her ikisinin birlikte kullanılmasıyla tedaviye başlandı ve 14 gün süreyle devam edildi. Tedavi prosedürü boyunca hayvanların diyare skorları kaydedildi. Deney sonrası sıçanların serum ve kolon dokularındaki NLRP3 seviyeleri ile kolon SOD seviyeleri değerlendirildi. Diyare skorunun kolit grubunda diğer gruplara göre anlamlı olarak yükseldiği; mesalamin+alfa lipoik asit grubunda ise anlamlı olarak azaldığı saptandı. Kolit grubunda, serum ve kolon dokusu NLRP3 seviyesinin en yüksek, kolon SOD seviyesinin ise en düşük seviyede olduğu belirlendi. Mesalamin+alfa lipoik asit grubunda bu parametrelerin diğer gruplara göre anlamlı olarak düzenlendiği görüldü. Sonuç olarak, kolit olgularında NLRP3 inflamazomunun arttığı, SOD düzeyinin azaldığı; alfa lipoik asitin mesalamin ile olan kombinasyonun bu değerler üzerine düzenleyici etkilerinin tek başına kullanımına göre daha iyi olduğu kanaatine varıldı.

Keywords

Alfa lipoik asit, diyare, kolit, inflamazom, oksidasyon

Ethical Statement

Gazi Üniversitesi Hayvan Deneyleri Yerel Etik Kurulu’ndan G.Ü.ET-24.037 onay numarası ve 30.04.2024 tarihiyle alınmıştır.

Supporting Institution

TÜBİTAK 2209-A

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