Fahad Bashraheel

Antioxidant and Antifibrotic Effect of a Herbal Formulation In Vitro and in the Experimental Andropause via Nrf2/HO-1 Signaling Pathway

The Korean herbal formulation Ojayeonjonghwan is used for improving late-onset hypogonadism (LOH) symptoms such as erectile dysfunction (ED). A previous research suggested that a modified Ojayeonjonghwan (KH-204) could be used as an alternative to the treatment for ED. The pharmacological effects were examined in different conditions, including in vitro and in vivo. We measured the survival rate of TM3 Leydig cells under the oxidative stress condition. The s.c. injection of leuprorelin was used to induce androgen deprivation. We measured serum testosterone levels, oxidative stress, and apoptosis. The results of the treatment by KH-204 (1) preserved TM3 cells from oxidative stress by improving the expression of nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1); (2) lowered the expression of transforming growth factor-beta (TGF-β) 1/SMAD; (3) increased the average of serum testosterone in androgen-deprived male rats; (4) kept the activation of spermatogenesis; (5) upgraded the contents of 8-hydroxy-20-deoxyguanosine (8-OHdG) and degraded the contents of superoxide dismutase (SOD); and (6) reduced apoptosis. We studied that KH-204 improved testicular dysfunction in LOH. It is likely, at least in part, to degrade oxidative stress through the Nrf2/HO-1 pathway. These findings may offer credible evidences for the use of new alternative therapies to treat LOH.

Effects of Next-Generation Low-Energy Extracorporeal Shockwave Therapy on Erectile Dysfunction in an Animal Model of Diabetes

Purpose Gene therapy, stem cell therapy, and low-energy extracorporeal shockwave therapy (ESWT) have been investigated as treatments for refractory erectile dysfunction (ED), but inconclusive evidence has been obtained. We investigated the effect of a next-generation electromagnetic cylinder ESWT device on an animal model of ED. Materials and Methods Diabetes mellitus (DM)-induced rats were divided into 3 groups: group 1, control; group 2, DM; and group 3, DM+ESWT. Rats were treated with ESWT 3 times a week for 2 weeks. After the treatment course, intracavernous pressure was measured and the corpus cavernosum and cavernous nerve were evaluated. Results In the DM group, all parameters predicted to be significantly lower in the ED model had statistically significantly decreased (p<0.01). As a measurement of erectile function, intracavernous pressure was evaluated. The DM+ESWT group exhibited significantly restored erectile function compared to the DM group (p<0.05). Moreover, ESWT treatment restored smooth muscle content, as assessed by Massons trichrome staining (p<0.05). Finally, corporal tissue and the dorsal nerve were evaluated by immunohistochemistry, Western blotting, and ELISA. After ESWT treatment, vascular endothelial growth factor (VEGF), endothelial nitric oxide synthase (eNOS), platelet endothelial cell adhesion molecule-1, cyclic guanosine monophosphate, and neuronal nitric oxide synthase (nNOS) expression levels were restored to levels in the DM group (p<0.05). Conclusions Electromagnetic cylinder ESWT device resulted in increased VEGF, nNOS, and eNOS expression; reduced smooth muscle atrophy; and increased endothelial cell regeneration in a DM-associated ED model. Our data suggest that safe and effective application could be possible in future clinical studies.

Lycium chinense Mill improves hypogonadism via anti-oxidative stress and anti-apoptotic effect in old aged rat model

Abstract Purpose: To evaluate the pharmacological effects of goji berry (Lycium chinense P. Mill) in an animal model of late-onset hypogonadism (LOH). Materials and methods: Thirty 18-month-old male Sprague–Dawley (SD) rats were used as the LOH aged rat model. Rats were divided into five groups: a control group (n = 6), low concentration goji berry extract group (150 mg/kg/day) (n = 6), high concentration goji berry extract group (300 mg/kg/day) (n = 6), low concentration goji berry complex extract group (150 mg/kg/day) (n = 6), and high goji berry complex concentration extract group (300 mg/kg/day) (n = 6). After six weeks of treatment, sperm counts and motility, serum testosterone level, androgen receptor (AR) expression, oxidative stress marker, and apoptotic factors were examined. Results: Goji berry extracts increased testosterone level to 2.07 ± 0.06 pmol/L in the goji berry 150 mg/kg group, 2.39 ± 0.08 pmol/L in the goji berry 300 mg/kg group, 2.97 ± 0.03 pmol/L in the goji berry complex 150 mg/kg group, and 3.34 ± 0.04 pmol/L in the goji berry complex 300 mg/kg group compared to 1.86 ± 0.03 pmol/L in the control group, respectively (p < .05). AR expressions were increased in testis tissue significantly but were not significant in prostate tissue. Conclusions: Goji berry might improve LOH by reversing testicular dysfunction via an anti-oxidative stress mechanism without inducing prostate disease.

Gender- and cholesterol-specific predictive value of body mass index in renal cell carcinoma: A multicenter study

Recently, there have been some reports on preoperative body mass index (BMI) and total cholesterol (TC) as a prognostic predictor for patients with renal cell carcinoma (RCC) but the topic is controversial and still poorly understood. So we analyzed the effects of BMI and TC on the prognosis of RCC.

AB099. Improvement of persistent detrusor overactivity after relief of bladder outlet obstruction treated by phytotherapeutic agent

Background Many patients with benign prostatic hyperplasia need treatment for remaining storage symptoms after surgery. Therefore, we evaluated the effect of plant combination on persistent detrusor overactivity (DO) after relief of bladder outlet obstruction (BOO). Methods Rats were assigned as three groups: control (n=6), persistent DO (n=6), and persistent DO treated with the plant combination (n=6) groups. Persistent DO after relief of partial BOO was made and 6 of them were orally administered with the plant combination. Results After 4-week treatment with the plant combination, significantly reduced DO by cystometry was observed compared with persistent DO group. Moreover, oxidative stress, pro-inflammatory cytokines, and M3 muscarinic receptor were significantly increased. Additionally, significantly decreased oxidative stress, pro-inflammatory cytokines, and M3 muscarinic receptor in the bladder were observed after treatment with the plant combination. Conclusions Treatment with the plant combination improves persistent DO after relief of BOO mediated by antioxidative and anti-inflammatory effect. Further study is necessary to identify exact mechanism of treatment effect of the plant combination.

AB098. Defocused low-energy shock wave can stimulate penile tissues to produce more energy for growth and proliferation in a DMED rat model

Background Defocused low-energy shock wave therapy (DL-ESWT) is a novel and potential way in regeneration medicine, and now it has been used in many areas which have demonstrated its unique superiority. At present, some researchers have applied ESWT to clinical therapy for erectile dysfunction (ED), which achieves satisfactory therapeutic effects. However, the metabolic change of corpus cavernosum with ESWT is still unclear. To investigate the metabolic change of corpus cavernosum with ESWT in a rat model of DMED induced by streptozotocin (STZ). Methods We divided human umbilical vein endothelial cells (HUVECs) in three groups. Group 1 is control group, without ESWT. Group 2 is half treated group, with ESWT for former three passages. Group 3 is full treated group, and we applied ESWT to HUVECs for every passage. After five passages, we collected the cells, supernatants and proteins for ELISA and Western blot. The DMED rats were randomly divided into 2 groups (N=10 per group): 1 DMED group, 2 DMED + ESWT group. The normal group (N=10, without STZ) is the control group. Erectile function and other expression experiments were carried out after STZ injection of 8 weeks. ESWT was repeated 3 times per week with one day’s break, for a total duration of 4 weeks. Immediately after recording of intracavernous pressure (ICP), the penis was then harvested for histologic analysis, ELISA and western blotting. Results The ratio of ICP/MAP was significantly higher in the ESWT group than in the DMED groups (P<0.05). Expression of growth factors increases after ESWT in vitro (P<0.05). ESWT can promote proliferation of endothelial cells in corpus cavernosum. The result was significantly higher in the ESWT group than in the DMED group (P<0.05). ESWT can improve cell metabolism in vivo. The expression of mitochondrial membrane proteins is higher in the ESWT group than in the DMED group (P<0.05). And the lactate concentration is higher in the ESWT group than in the DMED group (P<0.05). Conclusions There was a metabolic coupling between oxidative phosphorylation and anaerobic glycolysis of cells in the corpus cavernosum. And after ESWT there were a lot of lactic acid produced by anaerobic glycolysis of endothelial cells taking part in the tricarboxylic acid cycle of cells in corpus cavernosum, which could generate a great deal of energy to support growth and proliferation.

AB095. Antioxidant and antifibrotic effect of a herbal formulation in vitro and in the experimental andropause via Nrf2/HO-1 signalling pathway

Background A Korean herbal formulation, Ojayeonjonghwan, is used to treat late-onset hypogonadism (LOH) symptoms including erectile dysfunction (ED). A previous research suggested that a modified Ojayeonjonghwan (KH-204) could be used as an alternative to treatment for ED. Pharmacological effects of KH-204 were examined in different conditions, including in vitro and vivo (an androgen-deprived rat model). Methods We measured the survival rate of TM3 Leydig cells treated by KH-204 under the oxidative stress condition. The s.c. injection of leuprorelin was used to induce the androgen-deprivation. We removed and weighed the testes and epididymides, which would be used to histopathological examination, from the rats in experimental and control groups. Furthermore, we also measured serum testosterone levels, oxidative stress and apoptosis. Results The results of treated by KH-204: (I) preserved TM3 cells from oxidative stress by improving the expression of nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1); (II) lowered the expression of Transforming growth factor-beta (TGF-β) 1/SMAD; (III) increased the average of serum testosterone in androgen-deprived male rats; (IV) kept the activation of spermatogenesis; (V) upgraded contents of 8-hydroxy-20-deoxyguanosine (8-OHdG) and degraded contents of superoxide dismutase (SOD); and (VI) meaningfully reduced apoptosis. Conclusions We studied the efficacy of KH-204 as an alternative therapy to improve testicular dysfunction in LOH. The efficacies of KH-204 are likely, at least in part, to degrade oxidative stress through the Nrf2/HO-1 pathway. These findings may offer credible evidences for the use of new complementary and alternative therapies to treat LOH.

AB099. The anti-inflammatory and anti-microbial effects of the novel herbal formulation (WSY-1075) on chronic bacterial prostatitis rat model

Objective The aim of this study was to investigate the anti-inflammatory and anti-microbial effects of a new herbal formula (WSY-1075) in a chronic bacterial prostatitis rat model. Methods Thirty two male Wistar rats were used in the study. Experimental chronic bacterial prostatitis was induced by instillation of bacterial suspension (Escherichia coli 108 per mL) into the prostatic urethra. Animals were followed for 4 weeks. After the induction of prostatitis, the rats were randomly divided into one of four treatment groups: control (n=8), ciprofloxacin (n=8), WSY-1075 (400 mg/kg) (n=8), and WSY-1075 (400 mg/kg) + ciprofloxacin (n=8). After 4 weeks of treatment, the prostatic pro-inflammatory cytokine [tumor necrosis factor-α, interleukin (IL)-6, and IL-8] levels, anti-oxidant effects (superoxide dismutase) and histological findings were noted. Results The use of ciprofloxacin, WSY-1075, and WSY-1075 with ciprofloxacin showed statistically significant decreases in bacterial growth and improvements in the reduction of prostatic inflammation compared with the control group (P<0.05). The WSY-1075 with ciprofloxacin group showed a statistically significant decrease in bacterial growth and improvement in prostatic inflammation compared with the ciprofloxacin group (P<0.05). Conclusions These results suggest that WSY-1075 may have anti-inflammatory and antimicrobial effects, as well as a synergistic effect with ciprofloxacin. Therefore, we suggest that the combination of WSY-1075 and ciprofloxacin may be effective in treating chronic bacterial prostatitis to obtain a higher rate of treatment success.

AB070. Comparison of photoselective vaporization versus holmium laser enucleation for treatment of benign prostate hyperplasia in a small prostate volume

Objective Photoselective vaporization of the prostate (PVP) using GreenLight and Holmium laser enucleation of the prostate (HoLEP) is an important surgical technique for management of benign prostate hyperplasia (BPH). We aimed to compare the effectiveness and safety of PVP using a 120 W GreenLight laser with HoLEP in a small prostate volume. Methods Patients who underwent PVP or HoLEP surgery for BPH at our institutions were reviewed from May 2009 to December 2014 in this retrospective study. Among them, patients with prostate volumes <40 mL based on preoperative trans-rectal ultrasonography were included in this study. Peri-operative and post-operative parameters—such as International Prostate Symptom Score (IPSS), quality of life (QoL), maximum urinary flow rate (Qmax), post-void residual urine volume (PVR), and complications—were compared between the groups. Results PVP was performed in 176 patients and HoLEP in162 patients. Preoperative demographic data were similar in both groups, with the exception of PVR. Operative time and catheter duration did not show significant difference. Significant improvements compared to preoperative values were verified at the postoperative evaluation in both groups in terms of IPSS, QoL, Qmax, and PVR. Comparison of the postoperative parameters between the PVP and HoLEP groups demonstrated no significant difference, with the exception of IPSS voiding subscore at one month postoperatively (5.9 vs. 3.8, P<0.001). There was no significant difference in postoperative complications between the two groups. Conclusions Our data suggest that PVP and HoLEP are efficient and safe surgical treatment options for patients with small prostate volume.

AB097. KH-204 reduces oxidative stress-induced testicular apoptosis via ERK and Akt pathways

Objective A Korean herbal formulation, Ojayeonjonghwan, is used to treat late-onset hypogonadism (LOH) symptoms including erectile dysfunction (ED). A previous study demonstrated that a modified Ojayeonjonghwan (KH-204) could be developed as a therapeutic alternative medicine to improve ED. We examined the pharmacological effects of KH-204 in vitro and in an androgen-deprived rat model. Methods The survival rate of TM3 Leydig cells treated with KH-204 was measured based on oxidative stress. Androgen-deprivation was induced by s.c. injection of leuprorelin. After daily intake of KH-204 for four weeks, the testes and epididymides from rats in all groups were removed, weighed and subjected to histological examination. In addition, testosterone level, oxidative stress, and apoptosis were measured. Results The results showed that KH-204 protected TM3 cells from oxidative stress via activation of the ERK and Akt pathways. The level of testosterone and activation of spermatogenesis in androgen-deprived male rats were significantly enhanced, and germ cell apoptosis was reduced after treatment. Conclusions We investigated the effect of KH-204 as an alternative treatment to reverse testicular dysfunction in LOH. The therapeutic effects are likely, at least in part, attributable to reduced oxidative stress via ERK and Akt-dependent signaling pathways.