European Urology Today: June/July 2023

New concepts on complementary treatment for cystitis The effectiveness of natural compounds in ameliorating drug-induced cystitis/IC/OAB-symptoms

Yet, at the moment, none of these fulfilled the criteria for becoming an isolated marker, and combinations of several biomarkers will probably facilitate obtaining the appropriate level of specificity and selectivity to allow their use in clinical practice. [6] So far, we have successfully established animal models of cyclophosphamide- induced cystitis [7] and retinyl-acetate/ corticosterone-induced detrusor overactivity [8, 9]. In the experiments, several biomarkers were used to, analyse bladder urothelium, bladder detrusor muscle, urine, and the central micturition areas. The possible link between OAB and depression was revealed, opening new prospects for further studies on the disease. [8] “Due to the complex etiopathogenesis of these syndromes, studies are aimed at the biomarkers connected with either inflammation or nerve growth...” Traditional herbal drugs for refractory cystitis/OAB Nutraceuticals are defined as foods, plants or herbs that provide possible health benefits, including the prevention and treatment of chronic diseases. [10] Some of them have been reported to relieve IC symptoms and be potent modulators of OAB. The inclusion of herbal drugs into the treatment protocol has been proven to be an ambiguous act [5]. No competitive agents to the existing pharmacological treatment have been found and even promising options lack well- designed studies to confirm their efficacy. [11] Among several herbal compounds most recognised are Gosha-jinki-gan [12], Hachi-mi-jio- gan [13], resiniferatoxin or capsaicin. [14] In general, the herbal drugs are thought to have

poorer efficacy but also less adverse effects in comparison to common drugs [15], and are reported as a complementary treatment rather than a monotherapy. [15, 16] Only a few clinical trials have been published, e.g. Betschart et al. analysed Bryophyllum pinnatum for its safety and effectiveness [17], Xiao et al. studied Weng-li-tong [15], Chen et al. analysed cinnamon patches for OAB symptoms. Schloss used Urox ® (a herbal mixture of Crateva nurvala, Equisetum arvense and Lindera aggregate) for the treatment of nocturnal enuresis [18, 19], and Schoendorfer for OAB symptoms and urinary incontinence. [20] Worth recognising is also the possible role of other natural substances, e.g. L-arginine, or quercetin, that were reported to have potential to reduce some of the IC symptoms. [10] Several authors proposed also probiotics used for irritable bowel syndrome as a treatment option for IC with coexisting IBS due to the “organ cross-talk” theory. [21] In our experiments we reviewed the reversion of the effects of cyclophosphamide or corticosterone/retinyl-acetate by administration of herbal compounds, i.e. Asiatic acid [7], Urox ® [9], or Potentilla chinensis [22], and, most interestingly, cannabinoid ligands e.g. arachidonyl-2’-chloroethylamide (ACEA) [8] and GPR55 agonist, O-1602 [23]. The studies included analyses of conscious cystometry findings, measurements of urothelium thickness and bladder oedema, as well as selected biomarkers. For the first time, we revealed a positive influence of these compounds on major urodynamic findings, including characteristic for both cystometric and voiding phase, i.e. bladder basal pressure, inter-contraction interval, bladder compliance, detrusor overactivity index, non-voiding contraction amplitude, and voided volume. Administration of these agents successfully restored concentrations of several biomarkers both in bladder urothelium (e.g.

Haemorrhagic cystitis may take the form of a serious disease, origin of which comes from the effect of various agents on bladder mucosa, including chemotherapeutic drugs. The most common ones are cyclophosphamide and ifosfamide, toxicity of which is connected with urinary tracts and may lead to macroscopic haematuria in 7-53% of cases. [1] The effectiveness of the most recognisable method of treatment (i.e. mesna) remains controversial though. Finally, other alkylating agents like thiotepa or 9-nitrocamptothecin, and certain medications, e.g. penicillins and their derivatives, may be involved in the onset of haemorrhagic cystitis via an immunological mechanism, as well. [2] On the other hand, IC is a specific condition, symptoms of which tend to overlap with other genitourinary disorders like OAB, or endometriosis, making the diagnosis and appropriate treatment a truly challenging task. [3] Antimuscarinic drugs are well-known agents that earned their place in the nowadays management of IC/OAB. However, one should consider their side effects, leading to the phenomenon of the low proportion of patients still on drugs at 1-year observation. [4] Thus, it seems natural that new substances receive growing attention in the trend towards novel concepts of complementary medical treatment aimed at drug-induced cystitis and IC. [5] It is coherent with the finding that 75% of individuals affected take complementary medicines. [5] Biomarkers of IC/OAB Due to the complex etiopathogenesis of these syndromes, studies are aimed at the biomarkers connected with either inflammation or nerve growth, including urothelial differentiation proteins, proteoglycan proteins, urinary nerve growth factors, cytokines, and chemokines. [3,6] The most promising results were related to the diagnostic use of the nerve growth factor (NGF), the brain derived neurotrophic factor (BDNF), C-reactive protein (CRP), prostaglandins, and cytokines. [6]

Dr. Łukasz Zapala Clinic of General, Oncological and Functional Urology Medical University of Warsaw (PL)


Prof. Andrzej Wróbel 2nd Dept. of Gynaecology Medical University of Lublin (PL)


Prof. Piotr Radziszewski

Clinic of General, Oncological and Functional Urology Medical University of Warsaw (PL)


There is a growing need for further discoveries in the treatment modalities of drug-induced cystitis/ interstitial cystitis (IC)/overactive bladder (OAB).

EAU Section for Urologists in Office (ESUO)

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European Urology Today June/July 2023


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