Akademik Veri Yönetim Sistemi
MOLECULAR IMMUNOLOGY, cilt.181, ss.93-101, 2025 (SCI-Expanded)
Introduction Our aim was to investigate the protective effects of 18 beta-Glycyrrhetinic-acid (50 and 100 mg/kg i.g) on LPS-induced rat sepsis model by analyzing some immune mechanisms including inflammation, apoptosis, and oxidative stress parameters by different techniques such as Mallory's Trichome staining, ELISA, tissue biochemistry and Western Blotting. Methods Forty-eight Sprague Dawley rats divided into 6 groups as follows: (i) Control, (ii) DMSO, (iii) LPS induced-Sepsis, (iv) LPS induced-Sepsis+ 18 beta-GA 50 mg/kg, (v) LPS induced-Sepsis + 18 beta-GA 100 mg/kg, (vi) 18 beta-GA 100 mg/kg. The pro-inflammatory cytokine (IFN gamma, IL-1 ss, TNF- alpha) levels were measured by ELISA technique. All rat's lung tissues micrographed with Mallory's Trichome stain. Oxidative stress parameters (MDA, GSH, SOD, NRF2, and HO-1), TLR4 signaling, and apoptotic proteins (Bcl-2 and Caspase-3) were detected by using tissue biochemistry and Western blotting. Results LPS administration caused a significant increase in all pro-inflammatory cytokine and oxidant levels. Shedding of bronchiolar epithelium, thickening of alveolar septa and vascular dilatation in LPS groups' lung tissue were revealed according to the histopathological findings. The H-scores of 18 beta-GA50 +LPS and 18 beta-GA100 +LPS groups were significantly lower than LPS groups' (p < 0.05). When lung tissue protein expression profiles were analyzed for HO-1, TLR4, IL-1 beta, TNF-alpha, Bcl-2, and Caspase-3 expression was higher in the LPS group than in the control. In addition, NRF2 and Bcl-2 protein expressions were higher in control, DMSO and 18 beta-GA100 groups, while it was the lowest level in LPS group. Conclusion 18 beta-GA demonstrates significant protective effects against LPS-induced lung injury in rats by modulating various immune mechanisms. These findings indicate that 18 beta-GA, particularly at the higher dose, may be a potential therapeutic agent in managing sepsis by mitigating inflammation, oxidative stress, and apoptosis in lung tissue. The inflammation and oxidative stress parameters were decreased and the apoptotic markers were increased in treatment group. Further molecular studies should be performed to investigate the roles of some significant cellular signaling pathways.