Effect of curcumin on TLR4/NF-κB pathway and urinary epithelial barrier in rats with chronic urinary tract infection

  Objective  To investigate the effect of curcumin on urinary barrier and Toll-like receptor 4 (TLR4)/nuclear factor-κB (NF-κB) pathway in rats with chronic urinary tract infection.

  Methods  Totally 48 male Sprague-Dawley rats were randomly divided into a sham operation group and a model group (with intragastric administration of saline), a positive drug group (with intragastric administration of Sanjin Tablet – a Chinese traditional medicine for treatment of urinary tract infections at the dosage of 3.67 g/kg), and low, moderate and high dose curcumin groups (with intragastric administration of curcumin at dosages of 0.075, 0.15, 0.3 g/kg). The treatments were conducted once a day continuously for 14 days. The chronic urinary tract infection model was established by urethra injection of 0.1 ml Escherichia coli suspension (concentration: 1 × 10⁷/ml) in all the rats except for those of sham operation group. By the end of last treatments, the rats′ urine in six hours, specimens of venous blood and bladder tissue were collected for detections of urine volume, urinary leukocyte count, serum interleukin (IL)-6 and IL-8 with enzyme-linked immunosorbent assay (ELISA), and tissular NF-κB/E-cadherin/zonula occludens protein 1 (ZO-1) with Western blot.

  Results  Compared with the sham-operation rats, the model rats had significantly decreased urine volume (2.46 ± 0.35 vs. 3.47 ± 0.65), serum IL-6 (0.13 ± 0.03 vs. 0.26 ± 0.05) and IL-8 (0.53 ± 0.16 vs. 1.32 ± 0.33), bladder tissular E-cadherin (0.18 ± 0.02 vs. 0.69 ± 0.07) and ZO-1 (0.08 ± 0.02 vs. 0.43 ± 0.04) (all P < 0.05) but significantly increased urinary leukocyte count (115.69 ± 14.89 vs. 23.48 ± 3.58) and bladder tissular TLR4 (1.05 ± 0.11 vs. 0.23 ± 0.04) and NF-κB (0.86 ± 0.09 vs. 0.09 ± 0.01) (P < 0.05 for all). Significantly increased bladder tissular E-cadherin (0.35 ± 0.06) and ZO-1 (0.35 ± 0.05) were detected in the rats with moderate curcumin but decreased urinary leukocyte count (64.83 ± 7.43), serum IL-6 (0.18 ± 0.02) and IL-8 (0.68 ± 0.14), and bladder tissular TLR4 (0.35 ± 0.04) and NF-κB (0.33 ± 0.04) in the rats with moderate and high curcumin in comparison with those in the model rats (P < 0.05 for all).

  Conclusion  Curcumin may has anti-inflammatory effect by down-regulating TLR4/NF-κB pathway in rats with bacteria- induced chronic urinary tract infection.