Effect of probiotic Lactococcus lactis D4 administration on transforming growth factor-β1 (TGF-β1) expression in a rat model of unilateral ureteral obstruction-induced renal fibrosis

Abstract

Introduction: Unilateral ureteral obstruction (UUO) is a well-established animal model for studying renal fibrosis and obstructive nephropathy. Transforming Growth Factor-β1 (TGF-β1) plays a key role in renal fibro genesis by promoting fibroblast activation and extracellular matrix accumulation. Lactococcus lactis D4 is known for its immunomodulatory and anti-inflammatory properties; however, its effect on TGF-β1 expression in obstructive nephropathy remains underexplored. Objective: To investigate the effect of probiotic Lactococcus lactis D4 on TGF-β1 expression in renal tissue of rats subjected to UUO. Methods: A post-test-only randomized controlled design was used in 15 male Sprague-Dawley rats (170-220 g), divided into three groups (N=5 each): Control (laparotomy only), P1 (UUO without treatment), and P2 (UUO with Lactococcus lactis D4). The probiotic was administered orally at a dose of 8 × 10⁹ CFU/mL, 0.5 mL/day for 7 days. After 7 days, kidney tissues were collected for histopathological analysis. TGF-β1 expression was assessed using immunohistochemistry and quantified as the percentage of positively stained cells. Results: TGF-β1 expression was significantly different among groups (Control: 33.06±1.14%, P1: 42.67±1.67%, P2: 29.11±1.42%; P=0.000, ANOVA). Post-hoc analysis showed significant increases in TGF-β1 in P1 vs. Control (P=0.001) and significant reductions in P2 vs. P1 (P=0.000). Conclusion: Administration of Lactococcus lactis D4 significantly decreased TGF-β1 expression in the kidneys of rats with UUO-induced renal fibrosis, suggesting its potential as an antifibrotic agent in obstructive nephropathy.