Crocetin attenuating Urinary tract Infection and adherence of uropathogenic E. coli in NRK-52E cells via an inflammatory pathway

Urinary tract infections (UTI) are commonly treated with broad-spectrum antibiotics, but treatment has limitation due to causes of nephrotoxicity in uroepithelial cells. Recently, the researcher focuses their research on alternative therapy for the treatment of UTI. This study evaluated the anti-infectious effect of crocetin against adherence of pathogenic [2-¹⁴ C]-acetate labeled Escherichia coli (MTCC-729) to rat proximal renal tubular cells (NRK-52E cells) and explores the possible mechanism of action.

In vitro cytotoxicity and radio acetate labeled tests were performed on NRK-52E cells. The rats were divided into five different groups as follows: normal control (NC), disease control (DC), and various doses of crocetin (1.25, 2.5, and 5 mg/kg) treated group rats. White blood cells in blood, urine, and bacterial colony counts were estimated at regular intervals. Pro-inflammatory cytokines, such as interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), interleukin-10 (IL-10), and interleukin-8 (IL-8), were also estimated. In the current study, we estimated the mRNA expression of toll-like receptor-4 (TLR-4) and toll-like receptor-2 (TLR-2) in the renal and bladder tissues.

Crocetin significantly (p < .05) inhibited the adherence of E. Coli in NRK-52E cells. Crocetin suppresses the lipid peroxidation (LPO) 42% in cells treated with H₂ O₂ cells without crocetin. The white blood cells (WBC) count in blood and urine were augmented and crocetin treatment significantly (p < .05) reduced the WBC in urine and blood. The pro-inflammatory cytokines, such as IL-6, MCP-1, IL-10, and IL-8, significantly (p < .05) increased in the DC group and crocetin significantly (p < .05) reduced the pro-inflammatory cytokines. Dose-dependent treatment of crocetin significantly reduced the mRNA expression of TLR2 and TLR4 in the renal and bladder tissues.

Crocetin considerably reduced the bacterial adherence to NRK-52E cells, attenuated the H₂ O₂ induced toxicity in NRK-52E cells and also improved the renal tubular function, and reduced the inflammatory response via altering the inflammatory and antioxidant markers.

As we all know that urinary tract infection is the most common disease worldwide. In this study, we scrutinized the protective effect of crocetin against urinary tract infection. Crocetin treatment considerably reduced the zone of inhibition and improved radioactivity. Crocetin significantly reduced the levels of cytokines and inflammatory mediators. Crocetin can be used as a protective drug in the treatment of urinary tract infections.