Abstract

Abstract Background and Aims Urinary tract infections (UTIs) are estimated to account for over 7 million office visits per year. UTIs are about 50 times more frequent in women than in men, however, in men the incidence steeply increases after 50 years of age for prostate involvement. UTI diagnosis is based on symptoms and urinalysis. Antibiotic therapy is often required in subjects with relapsing UTIs. Therefore, it would be useful to develop a therapeutic strategy based on natural active compounds, free from side effects (such as on renal function), that could counteract UTIs recurrence. For this purpose, tannins (TNs) could represent a valid therapeutic alternative. TNs are polyphenolic compounds known for their anti-inflammatory, antimicrobial and antioxidant effects. Recent studies highlighted how TNs intake can counteract UTI recurrence, improving the quality of life. The aim of our study was to evaluate the beneficial action of chestnut TNs administered as oral food supplement (OFS) in recurrent UTI patients. Method OFS was characterized by HPLC/DAD/MS analysis for its content in secondary polyphenolic metabolites and by Folin-Ciocalteau in vitro tests for its antioxidative and anti-free radical activity with stable radical DPPH•. For in vivo tests, 16 chronic kidney disease (CKD) patients (8 female and 8 males) who suffered from recurrent UTIs, were recruited. The OFS was administered in 2 cps/ day, for 9 weeks. Patients were evaluated at T0= baseline and T1= after 9 weeks of OFS treatment. We performed laboratory and urinary tests, and the quality of life (SCL-90R questionnaire) and body composition (bioimpedentiometry) assessment. All parameters and questionnaires were evaluated at T0 and T1. At the same time, oxidative stress (OS) and antioxidant defenses were monitored using CR4000 (FORD and FORT tests). Results HPLC/DAD/MS quali-quantitative analysis allowed for an in depth chemical characterization of the individual polyphenols present in the OFS: total tannins amount is 10.542mg/g, whereas total anthocyanins are 1.885mg/g. The Folin Ciocalteu assay results show a total polyphenols content of 68.7mg/g GAE; the antiradical activity by DPPH assay is 94% for a solution 0.519mg/mL of powder. The epidemiological features of the population were reported in Table 1 and it was divided into two subgroups, according to gender. Laboratory parameters were reported in Table 2. During the study, we observed a drop out of three female subjects because of gastrointestinal (GI) disorders (nausea, gastric heartburn). We did not find any significative change in body composition parameters after OFS treatment. We highlighted a significant reduction (Table 3) of ESR only in male patients (16,7± 2,2 mm/h vs 11,3± 1,5 mm/h, p=0,0062). The urinalysis, showed a significant reduction of leukocytes in both subgroups (male: 43,5 (1-450) n/uL vs 15 ± 5,7 n/uL p = 0,0391; female: 28,5 (1-990) n/uL vs 7 (1-91) n/uL p= 0,0625) but urinary bacterial flora, after OFS supplementation significantly decreased only in male subjects (428 ± 143,4 n/uL vs 34 (0- 450) n/uL p= 0,0156). Interestingly we observed a significant reduction of OS parameters after OFS treatment as reported in Table 4. We also observed a reduction of the anxious and depressive components in male subjects in the SCL-90R questionnaire. Conclusion TNs seem to exert an antimicrobial action in a gender dependent manner, useful to counteract the recurrence of UTIs. OFS contains Serenoa repens, a substance with peripheral, antispastic and antiandrogenic action that could induce nausea and vomiting. Female patients dropped out for GI disorders had lower body weight and SR probably were overdosed for their body mass. In male subjects, the decrease in anxiety and depression at the end of the study, could be linked to the improvement of the urinary symptomatology. A randomized clinical trial conducted a larger population is needed to confirm these findings and explain the correlation with gender.

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