The effect of the hexanic lipidosterolic extract of Serenoa repens on the bladder function in partial bladder outlet obstruction.

Abstract

Introduction. It is believed that the «target» of the hexane extract of Serenoa repens (HESR) is the prostate gland itself. However, there is evidence in the literature that the therapeutic effect of HESR can be carried out at the level of the bladder. We hypothesized about the direct effect of HESR on the obstructive bladder, preventing the development of its dysfunction. Material and methods. The study was conducted on 30 white mongrel female rats. Bladder outlet obstruction (BOO) was modeled by applying a ligature to the urethra on 18G catheter. The animals were divided into groups: experimental – HESR (n = 10); sham/placebo (n = 15) and control (n = 5). From the day following the operation, rats of the experimental series daily received aqueous alcohol suspension of HESR (27.6 mg/kg) intragastrically through a probe, and the sham group received the same volume of 3.5% alcohol solution. After 2 weeks, the survival rate of the animals, the functional state of the bladder, daily diuresis, biochemical changes in blood and urine characterizing the functional state of the kidneys were evaluated. Bladder function was assessed according to infusion cystometry. After examination, the animals were euthanized and the bladders was removed to determine its mass and histological examination. Results. Within 2 weeks in the sham group 10 (67%) rats died due to renal failure, while in the HESR group – only 3 (30%). An obvious overfilling of the bladder in the main and sham groups was revealed. Bladder volume was larger in the HESR group compared to the sham (p<0.05) one. The daily diuresis of the animals of the main group was also higher compared to the sham group, and the decrease in diuresis in the sham group was lower compared to the control (p=0.045). The functional state of the bladder was assessed by filling cystometry. In the sham group, an increase in intravesical pressure occurred immediately after the start of fluid infusion and its growth was accompanied by irregular fluctuations, which is a manifestation of secondary detrusor hyperactivity, while in the HESR group, a gradual increase in pressure without fluctuations up to large volumes of fluid was observed. The dynamics of the volume/pressure index in the main group was close to normal, which indicates better compliance of the wall of the hypertrophied bladder during HESR therapy. The use of HESR contributed to better preservation of kidney function. In terms of daily diuresis, glomerular filtration rate, tubular reabsorption of sodium, daily excretion of urea and creatinine in the urine, statistically significant differences were established between the main and sham groups. In the sham group, a more pronounced activity of creatine phosphokinase was noted compared to the HESR group (p<0.05), which indicates a significant damage to kidney and bladder cells (cytolysis) during BOO. Animals of both groups showed pronounced detrusor hypertrophy. If in the sham group the mass of the bladder exceeded the average value of the control group by 5.7 times, then in the HESR group it was 10.5 times. Histological studies confirmed the development of bladder hypertrophy, which was statistically significantly more pronounced in the HESR group: an increase in the thickness of the detrusor (p<0.001) and bladder wall (p<0.05). At the same time, the area of perimuscular sclerosis foci was significantly larger in the sham group (p<0.05), which indicates bladder decompensation. Thickening of the bladder wall also occurred due to the submucosal layer, which was more noticeable in the sham series (p<0.05) and was associated with the presence of edema, inflammatory infiltrates, and sclerosis in this area. In half of the cases of the sham series, de-epithelialized areas of the bladder mucosa were observed, while in the HESR group they were absent. In the experimental series, in all samples, a pronounced expansion of the vessels of the submucosal layer was noted. At the same time, if in the experimental group inflammatory infiltration was detected only within the submucosal layer, then in half of the cases of the sham series, diffuse infiltration of the entire bladder wall was detected. Conclusion. In BOO detrusor hypertrophy, the use of HESR contributes to the better preservation of the functional parameters of the bladder (compliance and evacuation ability), reduces the degree of inflammation and sclerosis of the bladder wall, prevents the development of decompensation of the bladder and, thereby, contributes to the preservation of kidney function. A significant decrease in the frequency of development and the degree of detrusor hyperactivity against HESR makes it possible to think about it’s direct effect on the smooth muscle cells of the bladder wall and/or on the way of regulating their contractile activity. The mechanisms of the HESR effects on the BOO bladder are currently unclear. This is probably of a complex nature, where the anti-inflammatory effects of Serenoa Repens are expected to play a primary role.