Rehearsal For Thesis Presentation

Chronic kidney disease (CKD) is a kidney disease characterized by abnormal kidney function or structure lasting more than three months, leading to the accumulation of uremic toxin in the body. Indoxyl sulfate (IS) is a uremic toxin produced from tryptophan through the metabolism of indole by intestinal microbiota and the liver. Furthermore, it causes cytotoxicity and oxidative stress, resulting in systemic effects throughout the body. Probiotics, which are beneficial microorganisms for the host, have shown potential in improving kidney function in numerous studies. Therefore, the aim of this study is to select potential probiotic by ameliorating IS induced kidney cell toxicity in vitro and use combination of probiotic to improve adenine-induced CKD mice model. First, the study used the clearance ability of uremic toxin precursors indole and p-cresol to select four potential strains S4, S46, S53 and S90. Next, preparing cell-free supernatant (CFS) to evaluate the effects of IS-induced toxicity and oxidative stress in the NRK-52E renal tubular epithelial cell line. Results showed that the four strains could partially clear indole and p-cresol, moreover, Lacticaseibacillus paracasei S4, Lc. paracasei S90 and Lactiplantibacillus plantarum S53 significantly protecting against IS-induced renal cell toxicity. In vivo, the study used seven-week-old male C57BL/6 mice with preventive model. The mice were given probiotic containing 2×10⁹ CFU/mL Lc. paracasei RM081, 1×10⁸ CFU/mL Clostridium butyricum (CB), and 1×10⁹ CFU/mL of the three tested strains S4, S53, and S90. They also were fed the feed involved in 0.2% adenine for 18 days to induce CKD. The results showed that mice fed with 0.2% adenine diet had reduced food intake and significantly lower body weight compared to the control (Con) group (p < 0.05). Kidney tissue sections revealed cortical damage and fibrosis, with reduced damage scores observed in the S4 and S53 groups. S4 group showed a significant reduction in blood urea nitrogen (BUN) level, and all of the groups demonstrated decreasing blood creatinine concentration significantly (p < 0.05). Additionally, S4 group exhibited a trend of reducing fecal indole, p-cresol, and serum p-cresyl sulfate (PCS), and significantly reduced IS level (p < 0.05). S4 and S53 groups also significantly decreased serum fluorescein isothiocyanate-dextran (FITC-D) concentration (p < 0.05), indicating that intestinal barrier function and gut permeability were improved. In conclusion, the potential probiotic of Lc. paracasei S4, Lc. paracasei S90 and L. plantarum S53 can protect renal epithelial cell against IS induced damage, however, the combination of probiotic S4 group might be the most potential treatment in improving kidney function and gut permeability in CKD mice model.
 
Keywords: Chronic kidney disease, Uremic toxin, Indoxyl sulfate, Probiotic

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