Promoting Longevity in Aged Liver through NLRP3 Inflammasome Inhibition Using Tauroursodeoxycholic Acid (TUDCA) and SCD Probiotics

Abstract

This study investigates the combined impact of SCD Probiotics and tauroursodeoxycholic acid (TUDCA) on the biomolecular makeup, histological changes and levels of inflammasome in the liver tissue of 24-month-old male Sprague-Dawley rats. By administering TUDCA (300 mg/kg, intravenously) and SCD Probiotics (3 mL (1 x 108 CFU), orally) daily for a week, the researchers employed ATR-FTIR spectroscopy along with machine learning approaches such as Linear Discriminant Analysis (LDA) and Support Vector Machine (SVM) to analyze the biomolecular profiles. In addition, the study measured the expression levels of inflammasome markers NLRP3, ASC, Caspase-1, IL18, and IL1{beta} using RT-qPCR and examined liver sections for histopathological changes and NLRP3 inflammasome activation. The results revealed significant differences in the levels of lipids, proteins, and nucleic acids, with TUDCA having a noteworthy impact on enhancing lipid bands and reducing cholesterol ester bands, while SCD Probiotics showed the opposite effects. Furthermore, TUDCA was found to decrease the acyl chain length of fatty acids and improve protein conformation, whereas SCD Probiotics increased both the acyl chain length and protein phosphorylation ratio, suggesting a decrease in lipid and protein dynamics from both treatments. The histological assessments showed significant reductions in cellular degeneration, lymphatic infiltration, hepatic fibrosis, and the immunoreactivity of NLRP3 and ASC in the treated groups. SCD Probiotics exhibited a marked reduction in inflammasome-related gene expressions, and the lowest gene expression levels were observed in the group receiving both treatments. Despite an increase in serum AST and LDH levels across all groups, only the SCD Probiotics group showed an increase in albumin levels. The findings suggest that SCD Probiotics, TUDCA, and their combined administration may provide a promising avenue for therapeutic interventions in age-associated liver conditions and may mitigate age-related liver fibrosis while enhancing liver functionality.