Influence of Cranberry Extract on Tamm-Horsfall Protein in Human Urine and its Antiadhesive Activity Against Uropathogenic Escherichia coli.

LC-MS characterized cranberry extract from the fruits of Vaccinium macrocarpon inhibited under in vitro conditions the bacterial adhesion of Escherichia coli strain 2980 uropathogenic E. coli (UPEC strains UTI89, NU14) to T24 bladder cells and adhesion of UPEC strain CFT073 to A498 kidney cells in a concentration-dependent manner. Within a biomedical study, urine samples from 16 volunteers (8 male, 8 female) consuming cranberry extract for 7 d (900 mg/d) were analyzed for potential antiadhesive activity against UPEC by ex vivo experiments. Results indicated inhibition of adhesion of UPEC strain UTI89 to human T24 bladder cells. Subgroup analysis proved significant inhibition of bacterial adhesion in case of urine samples obtained from male volunteers while female urine did not influence the bacterial attachment. Differences between antiadhesive capacity of urine samples from male/female volunteers were significant. Protein analysis of the urine samples indicated increased amounts of Tamm-Horsfall protein (THP, syn. uromodulin) in the active samples. Inhibition of bacterial adhesion by the urine samples was correlated to the respective amount of THP. As it is known that THP, a highly mannosylated glycoprotein, strongly interacts with FimH of UPEC, this will lead to a decreased interaction with uroplakin, a FimH-binding transmembrane protein of urothelial lining cells. From these data it can be concluded that the antiadhesive effect of cranberry after oral intake is not only related to the direct inhibition of bacterial adhesins by extract compounds but is additionally due to an induction of antiadhesive THP in the kidney.

Urine uromodulin estimation in partial bladder outlet obstruction and cyclophosphamide-induced haemorrhagic cystitis models in rats.

INTRODUCTION: Uromodulin (UMOD) is a glycoprotein excreted by the thick ascending limb of the Henle's loop and distal convoluted tubule cells, playing various, yet still unclear roles. An abnormal urinary UMOD excretion is observed in many pathophysiological conditions. The aim of our study was to assess urine UMOD excretion in experimental partial bladder outlet obstruction (PBOO), reflecting BPH in humans, and in cyclophosphamide-induced haemorrhagic cystitis (CP-HC). MATERIALS AND METHODS: PBOO and CP-HC rats and two appropriate control groups were studied. The PBOO model was surgically induced by partial proximal urethral obstruction and CP-HC by four i.p. cyclophosphamide administrations (every two days). 24-hour urine collections were performed in both PBOO (on 3rd, 7th, 12th and 15th day after surgery) and CP-HC rats (on 1st, 3rd, 5th and 7th day). UMOD was determined with the ELISA method. Both 24-hour urinary UMOD excretion and urinary UMOD concentrations were determined. RESULTS: In the overall assessment, PBOO rats were characterized by decreased mean urinary UMOD concentration. However, as the urine volume, except for transient drop on 3rd day following PBOO operation, was steadily increasing, the daily urinary uromodulin excretion did not differ from the control one. Contrary to PBOO, CP-HC rats demonstrated mean urinary concentration similar to that of the control rats, while their 24hr UMOD excretion in urine was almost doubled due to urine volume increase (from 1.6 up to almost 3 fold). The highest UMOD urinary output was observed after the 3rd and 4th doses of cyclophosphamide. DISCUSSION: A reduced urinary UMOD excretion in early PBOO phase may be considered as a marker of distal tubular cells damage due to incomplete bladder emptying and increased pressure retrograding to distal tubules. This effect disappears with structural, adaptive histological changes of the bladder wall leading to an improved voiding. In CP-HC animals, the elevated urinary UMOD level may be associated with complex inflammatory response due to the cytotoxic CP action. UMOD assessment in this model may reflect renal and urological toxicity as UMOD excretion rises with the cumulative cyclophosphamide dose.

Modulatory effect of Chandraprabha Vati on antimicrobial peptides and inflammatory markers in kidneys of mice with urinary tract infection.

INTRODUCTION: Chandraprabha Vati (CV) is an Indian polyherbal Siddha drug, traditionally used as an anti-inflammatory agent for arthritis and urinary ailments. This study explores its effect on mice with urinary tract infection. MATERIALS AND METHODS: The in-organic constituents of CV were determined by atomic absorption spectroscopy and phytochemical analysis was carried out. The supplementing dose of CV to infected experimental mice was determined by in vitro antimicrobial assay. Transurethrally infected animals were supplemented with CV extract for 20 days after confirmation of UTI. The animals were euthanized as per the guidelines and the tissues were harvested from the control and infected mice for histopathological examination the antimicrobial peptide Tamm-Horsfall protein (THP) and inflammatory markers (tumor necrosis factor-α and nuclear factor kappa-light-chain-enhancer of activated B cells) to ascertain the modulatory effects of CV. Indicators for oxidative stress and protein levels were also quantified to validate the efficacy of CV. RESULTS: Terpenoids and flavanoids were majorly found to constitute CV along with zinc and iron as in-organic content. Histological and immunohistochemical studies confirmed the pronounced infection in the kidney of the uropathogenic Escherichia coli-infected animals. Supplementation of CV significantly restored the increased levels of the antimicrobial proteins, THP, and inflammatory markers. CONCLUSIONS: This study explored the efficacy of the aqueous extract of CV as an alternative medication for the synthetic analogues administered for UTI. This study also provides information on the possible role of THP as an antimicrobial protein in the kidney in preventing infection due to uropathogenic E coli.