Ahmet Gökçe

Protective effects of thymoquinone against methotrexate-induced testicular injury

Thymoquinone is the major active component derived from Nigella sativa. Methotrexate is a folic acid antagonist widely used in clinic. Aim of this study was to investigate the possible protective role of thymoquinone on testicular toxicity of methotrexate. Experiments were performed on male C57BL/6 mice (6 weeks old, 20 ± 2 g). The animals were divided into four groups with six mice in each group. Equivalent volumes of saline were injected intraperitoneally (i.p.) in the control group. In the thymoquinone group, mice received thymoquinone i.p. with a dose of 10 mg/kg/day for 4 days. Mice in the methotrexate group received single dose of methotrexate i.p., with a dose of 20 mg/kg. Finally, in the methotrexate plus thymoquinone group, in the first and the following 3 days after methotrexate administration, thymoquinone was injected with a dose of 10 mg/kg/day, i.p. At the end of the experiment, the left testis was quickly removed and divided into two parts for histological examination and biochemical analysis. Methotrexate alone increased total antioxidant capacity and myeloperoxidase activity compared to the controls. Thymoquinone treatment decreased total antioxidant capacity and prevented the increase in the myeloperoxidase activity. Light microscopy showed in mice that receiving methotrexate resulted in interstitial space dilatation, edema, severe disruption of the seminiferous epithelium and reduced diameter of the seminiferous tubules. Administration of thymoquinone reversed histological changes of methotrexate significantly. We suggest that thymoquinone use may decrease the destructive effects of methotrexate on testicular tissue of patients using this agent.

Protective Effect of Thymoquinone in Experimental Testicular Torsion

Objectives: To investigate the protective role of thymoquinone (TQ) on unilateral testicular ischemia-reperfusion (I/R) injury in mice. Materials and Methods: Experiments were performed on male C57BL/6 mice (8 weeks old, 20–25 g). The animals were divided into 3 groups including 6 mice in each group: control (sham), torsion/detorsion (TD) and TD+TQ. Mice, except the sham-operated group, were subjected to left unilateral torsion (720° rotation in the clockwise direction). The experiments were finished after sham operation time for controls, 120 min torsion and 240 min detorsion for the other groups. In the TD+TQ group 10 mg TQ was injected intraperitoneally 30 min before detorsion. Results: In the TD group total oxidative stress (TOS), oxidative stress index (OSI) and malondialdehyde (MDA) levels were higher than in the controls. TQ treatment decreased MDA, TOS and OSI values, but did not affect the total antioxidant capacity and myeloperoxidase activity in the TD+TQ group. Upon histological examination, mice in the TD group displayed moderate-to-severe disruption of the seminiferous epithelium. Treatment with TQ resulted in significantly reduced histological damage associated with I/R injury. Conclusion: Our results suggested that TQ treatment may have a protective effect on testicular I/R injury.

Protective effect of caffeic acid phenethyl ester on cyclosporine A-induced nephrotoxicity in rats.

Introduction. Cyclosporine A, an immunosuppressive agent, is widely used after organ transplantation such as the liver and kidney. However, its widespread use is restricted because it has serious toxic effects on the kidney. Caffeic acid phenethyl ester (CAPE) is a natural product with potent anti-inflammatory, antitumor, and antioxidant activities, and it attenuates inflammation and lipid peroxidation induced by ischemia-reperfusion injury. The purpose of the present study was to investigate the effects of CAPE on cyclosporine A (CsA)-induced nephrotoxicity. Material and Methods. Rats were divided into four groups and treated with saline, CAPE, CsA, and CsA + CAPE. Control rats were given saline; the CAPE group was given CAPE (10 μmol/kg/day) for 11 days intraperitoneally; the CsA group was given CsA (15 mg/kg/day) for 10 days subcutaneously; and the CsA+CAPE group was given CAPE for 11 days, and rats were s.c. injected with CsA in 0.5 ml of saline once a day for 10 days at the same time. Results. The administration of CsA alone resulted in higher myeloperoxidase (MPO) activity, lipid peroxidation, superoxide dismutase (SOD), and catalase (CAT) than in the control. The enzyme activities except CAT in rats treated with CAPE alone were not changed. CAPE treatment prevented the increase in malondialdehyde (MDA) and increased CAT activity more, but did not affect the activities of MPO and SOD enzymes. Discussion. CsA causes renal injury and CAPE prevents CAT- and lipid peroxidation-mediated nephrotoxicity via inhibition of oxidative process.

Update on Drug Interactions With Phosphodiesterase-5 Inhibitors Prescribed as First-Line Therapy for Patients with Erectile Dysfunction or Pulmonary Hypertension

Phosphodiesterase-5 inhibitors (PDE5i, sildenafil, vardenafil, tadalafil and avanafil) are a first-line medical therapy for erectile dysfunction (ED). In all likelihood, PDE5i usage will increase because sildenafil (Viagra® and Revatio®) and tadalafil (Cialis® and Adcirca®) have recently been recommended as first-line therapy for patients with pulmonary hypertension (PH). PDE5i exhibit higher plasma concentrations when co-administered with cytochrome P (CYP) 3A inhibitors, which influences their side-effect profile. The higher PDE5i plasma concentrations, caused by CYP3A inhibitors, influence the severity and timing of PDE5i drug interactions and require dose adjustment. PDE5i are safe when used with most antihypertensive agents, but co-administration with nitrates or α-blockers can cause severe hypotension and syncope. Dose adjustment is also necessary when PDE5i are co-administered with CYP3A inducers. The combination of oral tadalafil and bosentan (endothelin receptor antagonist) reduces tadalafil levels and requires dose adjustment. Current literature reports a number of interactions between PDE5i and other agents and further studies are needed to expand our knowledge base of these interactions. This review discusses relevant PDE5i drug interactions, including those with CYP 450 inhibitors and inducers which are frequently used during the treatment of ED and PH.

Beneficial effect of erdosteine on methotrexate-induced testicular toxicity in mice.

Methotrexate is used to treat certain types of cancer of the breast, skin, head and neck, or lung. Methotrexate can cause serious or life-threatening side effects on liver, lungs, kidneys, and immune system. Methotrexate chemotherapy causes testicular damage in humans. The aim of this study was to investigate the possible protective role of erdosteine on testicular toxicity of methotrexate in mice. Twenty-six male mice were divided into four groups as follows: group 1, control; group 2, erdosteine-treated; group 3, methotrexate-treated; and group 4, methotrexate + erdosteine treated. On the first day of experiment, a single dose of methotrexate was intraperitoneally administered to groups 3 and 4, although a daily single dose of erdosteine was orally administered to group 2 and 4 for 7 days. At the end of the experiment, the testes of the animals were removed and weighed. The levels of total antioxidant capacity and total oxidative stress, and myeloperoxidase activity in the methotrexate group were higher than the control group (p<0.05). Lipid peroxidation levels were not changed in methotrexate group compared with control group. In conclusion, erdosteine could effectively protect the testes in methotrexate-induced toxicity.

Hereditary Behavior of Varicocele

The inheritance of varicoceles and the potential transmission to first-degree relatives has rarely been investigated. In the present study, we examined the first-degree relatives of men with known varicocele to reveal the familial risk for varicocele. Of the patients with clinical varicocele who presented with infertility, testicular pain, or asymmetrical swelling of the scrotum between June 1, 2008 and May 31, 2009, 49 agreed to have their available first-degree relatives contacted for screening of varicoceles (n = 66). A cohort of 100 consecutive men who applied to the department of internal medicine between 2008 and 2009 for checkup procedure without a history of subfertility or a varicocele were used as a control population. Of the 92 first-degree relatives contacted, 66 (71.7%) decided to participate in this study. Of these 66 men, 21 (33.9%) had a palpable varicocele on physical examination. Compared with a control population (12%), the prevalence of palpable varicocele in the first-degree relatives of patients with known varicocele (33.9%) was approximately 3-fold greater (P < .005). Among the first-degree relatives, 4 (21.1%) of 19 fathers and 17 (36.2%) of 47 brothers had palpable varicocele. As a conclusion, a significant increase in varicocele prevalence is present in the first-degree relatives of men with known varicoceles. Patients should be counseled about this increased risk in male relatives of patients.

Effect of Thymoquinone on Oxidative Stress in Escherichia coli–Induced Pyelonephritis in Rats

BACKGROUND Recurrent urinary tract infections are important in children and adults with diabetes mellitus and/or incontinence due to risk of pyelonephritis (PYN) and renal damage. There is a positive correlation released free radicals during PYN and renal damage. Experimental studies showed that antioxidant agents improve renal damage when used immediately after bacterial inoculation. OBJECTIVE The aim of the present study was to evaluate whether treatment by thymoquinone (TQ) before or during Escherichia coli inoculation prevents oxidative damage in acute pyelonephritis (PYN) in an ascending obstructive rat model. METHODS In this study, 42 Wistar rats were grouped as follows: control, PYN (24, 48, and 72 hours), and TQ-PYN (24, 48, and 72 hours). E. coli (1 ×10(9) colony forming units) was inoculated into the bladder via urethral catheterization in both the PYN and TQ groups. TQ injections were performed 24 hours before bacteria inoculation and repeated at 24-hour intervals during the indicated time at a dose of 10 mg/kg body weight intraperitoneally in TQ groups. RESULTS Superoxide dismutase activity was statistically lower in the TQ-PYN-48 and -72 groups than the PYN-48 and -72 groups (P < 0.001, P = 0.004, respectively). Catalase activity was significantly higher in PYN-24, -48, and -72 groups than the control group (P < 0.001). In addition, there was a significant difference between the TQ-PYN-24, -48, and -72 groups and PYN groups in terms of glutathione peroxidase activity (P < 0.001, P = 0.026, P = 0.046, respectively). When the TQ-PYN-72 group was compared with the PYN-72 group, malondialdehyde levels were significantly lower in the TQ-PYN-72 group than in the PYN-72 group (P = 0.033). A histologic examination also confirmed the protective effect of TQ. In statistical analysis of histopathologic findings, there were significant differences between the PYN-24 and TQ-PYN-24, PYN-48 and TQ-PYN-48, and PYN-72 and TQ-PYN-72 groups (P = 0.008, P < 0.001, P < 0.001, respectively). CONCLUSIONS The results indicate that TQ administration attenuated the oxidative damage that occurred in PYN and, therefore, could be used as a supportive agent to protect the kidneys from oxidative damage caused by PYN.

Childhood Enuresis is Associated with Shorter Intravaginal Ejaculatory Latency Time in Healthy Men

PURPOSE In our previous study we showed that there was a significant increase in the prevalence of monosymptomatic enuresis among lifelong premature ejaculators. In this study we compared the intravaginal ejaculatory latency time of men with and without a history of monosymptomatic enuresis, and determined the association between the severity and duration of monosymptomatic enuresis and intravaginal ejaculatory latency time in healthy men. MATERIALS AND METHODS Between March and September 2012 we designed a prospective study in 49 healthy men who had a history of monosymptomatic enuresis and in age matched 49 control cases without a history of monosymptomatic enuresis. All subjects were asked about their history of monosymptomatic enuresis. Each subject was then evaluated using the premature ejaculation diagnostic tool and asked to measure their intravaginal ejaculatory latency times with their female sexual partner using a calibrated stopwatch. RESULTS Men with a history of monosymptomatic enuresis and control cases had a mean age of 33.6 (SD 4.7, range 25 to 43) and 33.8 (SD 5.4, range 25 to 48) years, respectively (p = 0.97). Mean/median intravaginal ejaculatory latency times of men with and without a history of monosymptomatic enuresis were 196.9/126.2 and 426.6/343.2 seconds, respectively (p <0.001). Mean/median premature ejaculation diagnostic tool scores of men with and without a history of monosymptomatic enuresis were 7.1/6 and 2.3/2, respectively (p <0.001). In correlation matrix analysis, intravaginal ejaculatory latency times and premature ejaculation diagnostic tool scores were correlated significantly with monosymptomatic enuresis history, duration and severity (p <0.001). CONCLUSIONS We found that intravaginal ejaculatory latency time in men with a history of monosymptomatic enuresis is significantly shorter than that of controls. We have also shown that there is a strong negative correlation between having a history of monosymptomatic enuresis and intravaginal ejaculatory latency time.

Value of preoperative stone scoring systems in predicting the results of percutaneous nephrolithotomy.

Introduction Guys Stone Score and S.T.O.N.E. Nephrolithometry nomograms have been introduced for systematic and quantitative assessment of kidney stones. The aim of this study was to reveal the value of two scorings systems, Guy and S.T.O.N.E, most frequently used for predicting postoperative stone-free status prior to Percutaneous Nephrolithotomy (PCNL), in the prediction of postoperative results of PCNL. Material and methods We retrospectively examined patients who underwent PCNL. Preoperative abdominopelvic computerized tomography images of these patients were reviewed and scored according to the Guy and S.T.O.N.E. systems. The relationship between the Guy and S.T.O.N.E. scores, and their postoperative stone-free status, complications based on Clavien system, operation time, fluoroscopy time and period of hospitalization was compared. Results We identified a total of 102 patients who underwent PCNL between 2010 and 2014, having met the inclusion criteria. The relationships between the total S.T.O.N.E score and Clavien score (p <0.001); time of operation (p = 0.012) and stone-free status (p <0.001); Guy stone score and Clavien score (p <0.001); and period of hospitalization (p <0.001) and time of operation (p <0.001) were found to be statistically significant. There was no statistically significant relationship between Guy score and stone-free status and no statistically significant relationship was found between fluoroscopy time and both stone scoring systems. Conclusions Guy and S.T.O.N.E. scoring systems may be used as effective instruments particularly for predicting postoperative complications.

Salt and nitric oxide synthase inhibition-induced hypertension: kidney dysfunction and brain anti-oxidant capacity.

The specific aim of this study was to examine the effects of salt-loading on kidney function and brain antioxidant capacity. Wistar rats were divided into four groups: Control rats were given normal drinking water and no drug treatment for 2 weeks. LNNA group: rats were given normal drinking water and the nitric oxide (NO) inhibitor NG-nitro-L-arginine (L-NNA), 3 mg/kg/day. LNNA + Salt group: rats were given drinking water containing salt 2% and 3 mg/kg L-NNA. Salt group: rats were given drinking water containing salt 2% and no drug treatment. Basal blood pressure and the levels of serum BUN, creatinine, uric acid, cortisol, electrolyte, serum antioxidant capacity, and oxidative stress were measured. NO, superoxide dismutase (SOD), and catalase (CAT) levels were measured in the hypothalamus, brainstem, and cerebellum. Salt overload increased the blood pressure of the LNNA + Salt group. Salt-loading enhanced BUN, creatinine, sodium retention. High salt produced an increase in uric acid levels and a decrease in cortisol levels in serum. Additionally, the oxidative stress index in serum increased in the LNNA + Salt group. Salt-loading enhanced brain NO levels, but not SOD and CAT activity. L-NNA increased brain SOD activity, but not CAT and NO levels. In conclusion, salt-loading causes hypertension, kidney dysfunction, and enhances oxidative stress in salt-sensitive rats.