Aim of our homework is to understand molecular mechanism of urinary tract infections, especially the usefulness of cranberry juice or tablets in preventing recurrent UTIs .
During evolution, distinct uropathogenic microbes predominantly derived from the gut microflora, have developed potent strategies to undermine the urogenital immune defence . Thanks to the recent discoveries concerning molecular mechanism underlying UTI, it has been possible to implement new preventive strategies.
Cranberries (Vaccinium macrocarpon Ait.) have been used widely for several decades for the prevention and treatment of urinary tract infections.
The Cochrane Collaboration evidences that cranberry juice may decrease the number of recurrent symptomatic UTIs over a 12 month period, particularly for young and middle-aged women. After that, a lot of studies compare cranberry juice and capsules with placebo, juice or water. Meta-analyses have established that recurrence rates over 1 year are reduced approximately by 35% in young to middle-aged women. However, there is a non-significant reduction of UTIs associated with Vaccinium macrocarpon treatment during pregnancy. The efficacy of cranberry in other groups (i.e. elderly, paediatric patients, those with neurogenic bladder, those with chronic indwelling urinary catheters) is questionable. Despite this, some studies about use of cranberry tablets for the prevention of UTIs in spinal cord injured patients concluded that the extract should be considered for the prevention of UTIs in those patiens with neurogenic bladder. Moreover patients with a high GFR may receive the most benefit.
But, which mechanism is involved? Traditionally, the juice was thought to cause acidification of the urine increasing excretion of hippuric acid as potential antimicrobial mechanisms. Moreover ascorbic acid in the cranberry juice may facilitate non-enzymatic generation of nitric oxide (NO) which possesses potent antimicrobial activities. The growth of E. coli was markedly inhibited in mildly acidified urine when nitrite was present.
Nevertheless, recently it has been discovered that cranberries contain a substance that can prevent bacteria from sticking on the walls of the bladder. Bacterial antiadhesion activity is operated by a group of proanthocyanidins (PACs) with A-type linkages against both antibiotic susceptible and resistant strains of type I and P-fimbriated UPEC [6] [7]. Proanthocyanidins contain alpha-Gal(1-->4)beta-Gal receptor sequences similar to those on epithelial cells in the urinary tract [9].
Cranberry juice alters also the conformation of the surface macromolecules on E. coli HB101pDC1 (mutant with P-fimbriae). The equilibrium length of polymer (P-fimbriae) on this bacterium decreased from approximately 148 to approximately 48 nm upon being exposed to cranberry juice. Highly acidic conditions were not necessary for the prevention of bacterial adhesion, since neutralization of cranberry juice solutions to pH = 7.0 allowed us to observe differences in adhesion between the E. coli strains.
Besides, activated macrophages increase the expression of COX-2 and iNOS in response to bacterial infection and inflammation that can be attenuated in a dose-dependent way by the amount of PAC loaded into the chitosomes of the LPS-stimulated macrophages.
Some authors discussed the potential interaction between warfarin and cranberry juice. Specifically, cranberry juice may inhibit the activity of CYP2C9, the primary isoenzyme involved in the metabolism of warfarin. In spite of this, the available data do not seem to show a clinically relevant interaction between cranberry juice and warfarin.
Little is known about the dose range of the antimicrobial effect. Furthermore, it has not been studied directly in the urogenital system. A study suggests that proathocyanidins can inhibit E. coli adherence to biologically relevant model systems of primary cultured bladder and vaginal epithelial cells. This effect occurs in a dose dependent relationship.
To conclude, cranberry treatment is a safe, well-tolerated supplement that does not have significant drug interactions. Although investigations are in the early stages, experimental and preclinical studies suggest that cranberry components may have other potential benefits, including anti-infective, anticancer and antioxidant effects, which may be considered as positive for different age-related conditions. In addition, cranberry components may induce positive cardiovascular and metabolic changes, and may improve neuropsychological activity. These results suggest further clinical researches with the purpose to valorize the role of the products extracted by cranberries for women’s treatment.
REFERENCES
Martina Ferraresi
Fabrizio Mele
