Additive effect of oral LDD175 to tamsulosin and finasteride in a benign prostate hyperplasia rat model

Abstract

ObjectiveWe investigated the benefits of the BKCa agonist 4-chloro-7-trifluoromethyl-10H-benzo[4,5]furo[3,2-b]indole-1-carboxylic acid (LDD175) combined with tamsulosin and finasteride, in a benign prostatic hyperplasia (BPH) rat model.Materials and methodsCastration was performed by bilateral orchiectomy under ketamine anesthesia. A rat model of BPH was established by daily intramuscular administration of testosterone propionate plus 17β-estradiol for 8 weeks. Model rats were administered combinations of 20 mg/kg LDD175, 0.01 mg/kg tamsulosin and 1 mg/kg finasteride once daily by oral gavage for 4 weeks from week 6 to 9 post-surgery. Intraurethral pressure induced by electrostimulation of the hypogastric nerve was measured at the end of administration. Body and genitourinary organ weights were recorded, serums were assayed for hormone concentrations, and tissues were subjected to histopathology, and analyses of α1-adrenoceptor mRNA and protein expression levels after treatment.ResultsCombined LDD175, tamsulosin, and finasteride significantly decreased prostatic index, serum hormone levels, epithelial thickness, and prostate expression of α1-adrenoceptors in BPH model rats. The 3-drug combination was more effective than any other combination or LDD175 alone.ConclusionThese results suggest that LDD175 addition to tamsulosin and finasteride may be beneficial for the treatment of BPH patients who do not respond to tamsulosin plus finasteride.

Origanum majorana L. Extract Attenuated Benign Prostatic Hyperplasia in Rat Model: Effect on Oxidative Stress, Apoptosis, and Proliferation

“…The G*Power program for Windows (version 3.1.9.7) was used to compute the sample size according to the procedures specified [ 32 ]. Following previous studies [ 5 , 33 , 34 , 35 , 36 , 37 ], we assumed that the means for five groups (vehicle, BPH, finasteride, O. majorana 250 and 500 mg/mL) would be (5.50, 10.17, 7.50, 23.82, and 5.63) for MDA, and (800.05, 567.06, 658.23, 115.20 and 991.462) for SOD. Considering the standard deviation (SD) within each group, 1.24 for MDA and 105.168 for SOD, effect size (f) would be 4.67 for MDA and 2.635 for SOD.…”

Inhibition of α1‐adrenoceptor reduces TGF‐β1‐induced epithelial‐to‐mesenchymal transition and attenuates UUO‐induced renal fibrosis in mice

“…Sham‐operated mice had their ureters exposed and manipulated but not ligated. Tamsulosin was injected intraperitoneally to mice at the dose of 0.4 mg/kg/day 13 . The same amount volume of corn oil was administrated as sham control.…”

“…Tamsulosin was injected intraperitoneally to mice at the dose of 0.4 mg/kg/day. 13 The same amount volume of corn oil was administrated as sham control. The kidneys and plasma were harvested at days 7 and 14 after UUO.…”

Multivitamin and Mineral Supplementation Containing Phytonutrients Scavenges Reactive Oxygen Species in Healthy Subjects: A Randomized, Double-Blinded, Placebo-Controlled Trial

“…Quantitative polymerase chain reaction (qPCR) array was performed using AccuPower ® Customized qPCR Panel Kit (Bioneer, Daejeon, Korea) as described previously [27]. Briefly, total RNA was extracted using a TRIZOL reagent (Invitrogen Co., Carlsbad, CA, USA).…”