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Introduction. Bladder outlet obstruction (BOO) occurs in more than 20 percent of the adult population and may lead to changes in the structure and function of the bladder. The main objective of the study was to evaluate the expression of Toll-like receptor 4 (TLR 4) and Toll-like receptor 9 (TLR 9) in the animal model of BOO as potential triggers of the inflammation phase in the bladder. In addition, the modulating effect of alpha-1 adrenergic antagonist (tamsulosin) on TLR 4 and TLR 9 expression and inflammatory markers was assessed. Material and Methods. Thirty-two male, 9-week-old Sprague Dawley rats were randomly divided into 4 groups: SOP—sham-operated rats with a placebo (water); SOB—sham-operated rats with an alpha-1 adrenergic antagonist; BOOP—rats with BOO and a placebo; and BOOB—rats with BOO and an alpha-1 adrenergic antagonist. The rats were given a placebo or alpha-1 adrenergic antagonist for 15 days. Next, urine and the bladder were collected from the rats for histopathological and biochemical study. Results. Histopathological analysis showed chronic inflammation without acute inflammation in the bladder. TLR 4 showed positive cytoplasmic reactivity in the urothelium and the smooth muscles of the bladder. TLR 9 showed positive cytoplasmic reactivity only in the urothelium. BOO caused an increase in TLR 4 and TLR 9 expression. Furthermore, treatment with an alpha-1 adrenergic antagonist had no significant effect on TLR 4 and TLR 9 expression in rats with BOO. BOO caused a significant increase in urine concentration of interleukin 6 (IL-6), while alpha-1 antagonist reduced the urine concentration of IL-6 and the concentration of interleukin 18 (IL-18). Conclusions. The results suggest the participation of TLR 4 and TLR 9 receptors in the induction of inflammation in the bladder, which is the first phase in the development of pathophysiological changes in BOO.

Multiple sclerosis (MS) is an autoimmunological disease leading to neurodegeneration. The etiology of the disease remains unknown, which strongly impedes the development of effective therapy. Most MS treatments focus on modulating the activity of the immune system. Dimethyl fumarate (DMF) exerts a broad spectrum of action, such as modulating immune cell differentiation towards anti-inflammatory subtypes, influencing cytokine production, regulating immune cell migration into the central nervous system, and activating intracellular antioxidant mechanisms. It is well established that activation of the nuclear factor E2 (Nrf2)-dependent pathway, leading to expression of the second-phase antioxidant enzymes, is influenced by DMF. In our experiments we used female Lewis rats in an animal model of MS - experimental allergic encephalomyelitis (EAE). The rats were fed with dimethyl fumarate to test the expression of heme oxygenase-1 (HO-1), one of the second-phase antioxidant enzymes, at specific time points of the symptomatic phases of the disease: on the first day of the occurrence of clinical symptoms (10th day post immunization, DPI); at the peak of clinical symptoms (14th DPI); and at the end of the relapse (21st DPI). The results showed that HO-1 expression, at both the mRNA and protein level, is influenced by DMF administration only at the very beginning of the symptomatic phase of EAE, and not at the peak of clinical symptoms, nor at the end of the relapse. This indicates that the regulation of the Nrf2-dependent antioxidant pathway by DMF occurs at a certain time interval (early EAE/MS) and strongly underlines the importance of the earliest introduction of the therapy to the patient. .