Emin Ozbek

Protective effect of curcumin in cisplatin-induced oxidative injury in rat testis: mitogen-activated protein kinase and nuclear factor-kappa B signaling pathways

BACKGROUND The aim of this study was to investigate the cellular/biochemical mechanisms by which cisplatin (CIS) causes testicular toxicity. We evaluated the role of inducible nitric oxide synthase (iNOS) expression, mitogen-activated protein kinase (MAPK) and nuclear factor-kappa B (NF-kB) activation in the pathogenesis of testicular damage induced by CIS, and investigated the effects of curcumin (CMN) against CIS-induced testicular injury in rats. METHODS Rats were divided into five equal groups: (1) control, (2) CIS, (3) CMN, (4) CIS + CMN and (5) CIS + corn oil. After the treatment, body and testicular weights, and plasma testosterone levels were observed, along with the biochemical, histopathological and immunohistochemical changes in testes. RESULTS Testicular weight, plasma testosterone levels, activities of glutathione peroxidase (GSH-Px) and glutathione (GSH) levels significantly decreased, whereas the level of malondialdehyde (MDA) and nitric oxide (NO) significantly increased with CIS compared with the controls. A significant increase in plasma testosterone levels, GSH levels and GSH-Px activity, and a decrease in MDA and NO levels in testicular tissue were observed with CIS + CMN compared with that with CIS alone. There was marked staining for iNOS, MAPK/p38 and NF-kB/p65 expression with CIS compared with the control and CIS + CMN groups. CIS caused irregular seminiferous tubules, reduction of seminiferous epithelial layers, significant maturation arrest and perivascular fibrosis. CMN administration to CIS-treated rats significantly prevented these histopathologic changes. CONCLUSIONS MAPK and NF-kB activation have a significant role in CIS-induced testicular toxicity. CMN has a strong potential for use as a therapeutic adjuvant in CIS gonadotoxicity.

Melatonin administration prevents the nephrotoxicity induced by gentamicin.

Objective To investigate the effect of melatonin on the antioxidant enzyme activity and renal tubular necrosis induced by gentamicin.

Potential chemoprotective effect of melatonin in cyclophosphamide- and cisplatin-induced testicular damage in rats.

OBJECTIVE To evaluate the effect of melatonin on cyclophosphamide (CP)- and cisplatin-induced testicular toxicity with use of sperm parameters and biochemical and histopathologic approaches. DESIGN Experimental study. SETTING Vakif Gureba Hospital, Istanbul, Turkey. ANIMALS Six-week-old adult male Wistar albino rats (N = 48). INTERVENTION(S) Cyclophosphamide was administered to rats by gavage at a single dose of 100 mg/kg body weight, only once. Cisplatin was injected intraperitoneally at single doses of 7 mg/kg/d for five consecutive days. Melatonin was both administered separately and coadministered with CP and cisplatin intraperitoneally at a dose of 10 mg/kg body weight. MAIN OUTCOME MEASURE(S) Body and testicular weight, epididymal sperm characteristics, plasma T, and histopathologic structure of the testicular tissue were determined. Malondialdehyde (MDA) and reduced glutathione (GSH) levels and glutathione peroxidase (GSH-Px) activity were assessed in testicular tissue. RESULT(S) Body and testicular weight, epididymal sperm count, motility and morphology, plasma T levels, the activities of GSH-Px, and GSH levels were significantly decreased whereas the level of MDA was significantly increased in rats of the CP and cisplatin group. Melatonin treatment increased GSH levels and GSH-Px activity, decreased MDA level in testicular tissue, and increased plasma T level. Cyclophosphamide and cisplatin caused irregular seminiferous tubules, reduction of seminiferous epithelial layers, significant maturation arrest, and perivascular fibrosis. Melatonin significantly improved histopathologic changes. CONCLUSION(S) Melatonin may prevent CP- and cisplatin-induced testicular damage.

Atorvastatin Prevents Gentamicin-Induced Renal Damage in Rats through the Inhibition of p38-MAPK and NF-kB Pathways

Background and aims. Gentamicin (GM) is still considered to be an important antibiotic against life-threatening, gram-negative bacterial infections despite its known nephrotoxic effects. We aimed to evaluate the potential protective effect of atorvastatin (ATO) against GM-induced nephrotoxicity in rats. Materials and methods. The rats were randomly divided into five groups of six animals each: control, GM (100 mg/kg/day), ATO (10 mg/kg/day), GM + ATO, and GM + Vehicle. Kidney function tests, tissue oxidative stress parameters, and histopathological and immunohistochemical studies clarified GM nephrotoxicity. Results. GM caused a marked reduction in renal functions and increased oxidative stress parameters. Histopathological examination revealed tubular necrosis especially in the renal cortex in GM rats. On immunohistochemical evaluation, GM rat showed more intense expressions of mitogen-activated protein kinase (MAPK), nuclear factor kappa B (NF‐kB), and inducible nitric oxide synthase (iNOS) compared with control. Kidney function tests and tissue oxidative stress parameters were normalized in the GM + ATO group. Histopathological and immunohistochemical pictures were also greatly ameliorated. Conclusions. ATO acts in the kidney as a potent scavenger of free radicals to prevent the toxic effects of GM via the inhibition of MAPK and NF-kB signaling pathways and iNOS expression.

Increased Plasma Adrenomedullin Levels in Patients with Behçet’s Disease

Background: Behçet’s disease (BD) is a chronic systemic inflammatory disorder affecting multiple organs with a generalized vasculitis of arteries and veins. Endothelial dysfunction is one of the prominent features of BD. Adrenomedullin (AM) is a peptide produced not only in normal adrenal medulla but also in the vascular smooth muscle cells and endothelial cells, and its role in the course of BD has not been previously described. Objective: To detect changes of plasma AM concentrations in patients with BD compared with age- and sex-matched healthy subjects by using high-performance liquid chromatography (HPCL). We also investigated if disease activity or the duration of BD correlates with AM levels. Methods: Forty-two consecutive patients with BD (38.5 ± 11.1 years, 19 male and 23 female) and 20 healthy age- and sex-matched control subjects (39.5 ± 10.9 years, 8 male and 12 female) were included in this study. We measured plasma AM levels by HPCL, and acute-phase reactants including α1-antitrypsin and α2-macroglobulin, neutrophil count and the erythrocyte sedimentation rate. Results: Mean ± SD plasma AM levels in patients with BD (73.22 ± 25.55 pmol/l) were significantly higher (p < 0.001) than in healthy control volunteers (21.35 ± 12.37 pmol/l). Patients with active BD had similar plasma AM concentrations (79.32 ± 21.89 pmol/l) with patients with inactive disease (67.44 ± 29.92 pmol/l). On the other hand, patients with longer duration of the disease (mean duration, 13.9 ± 3.8 years) had significantly higher plasma AM levels (83.99 ± 19.71 pmol/l; p = 0.005) than patients (62.45 ± 26.57 pmol/l) with shorter duration of the disease (mean duration, 5.5 ± 2.3 years). All acute-phase reaction parameters were found to be significantly increased in the active disease. Conclusion: Considering its endothelial cell implications, AM may be involved in reparatory vessel endothelium mechanisms, especially in the chronic disease.

Possible association of the 5-HTTLPR serotonin transporter promoter gene polymorphism with premature ejaculation in a Turkish population

We evaluated the genotypes of the serotonin transporter gene (5-HTT) in patients with premature ejaculation (PE) to determine the role of genetic factors in the etiopathogenesis of PE and possibly to identify the patient subgroups. A total of 70 PE patients and 70 controls were included in this study. All men were heterosexual, had no other disorders and were either married or in a stable relationship. PE was defined as ejaculation that occurred within 1 min of vaginal intromission. Genomic DNA from patients and controls was analyzed using polymerase chain reaction, and allelic variations of the promoter region of the serotonin transporter gene (5-HTTLPR) were determined. The 5-HTTLPR (serotonin transporter promoter gene) genotypes in PE patients vs. controls were distributed as follows: L/L 16% vs. 17%, L/S 30% vs. 53% and S/S 54% vs. 28%. We examined the haplotype analysis for three polymorphisms of the 5-HTTLPR gene: LL, LS and SS. The appropriateness of the allele frequencies in the 5-HTTLPR gene was analyzed by the Hardy-Weinberg equilibrium using the chi2-test. The short (S) allele of the 5-HTTLPR gene was significantly more frequent in PE patients than in controls (P<0.05). We suggest that the 5-HTTLPR gene plays a role in the pathophysiology of all primary PE cases. Further studies are needed to evaluate the relationship between 5-HTTLPR gene polymorphism and patient subgroup (such as primary and secondary PE) responses to selective serotonin reuptake inhibitors as well as ethnic differences.

Melatonin Attenuates Unilateral Ureteral Obstruction–Induced Renal Injury by Reducing Oxidative Stress, iNOS, MAPK, and NF-kB Expression

PURPOSE To investigate whether melatonin (MLT) treatment has any protective effect on unilateral ureteral obstruction (UUO)-induced kidney injury in rats. MATERIALS AND METHODS Six animals were included in each of the following five groups: group 1, sham operation but no treatment; group 2, unilateral ureteral ligation but no treatment; group 3, sham operation + MLT; group 4, unilateral ureteral ligation + MLT; group 5, unilateral ureteral ligation +5% ethanol (the vehicle of MLT). The injected dose of MLT was 1 mg/kg/day (intraperitoneal). MLT and vehicle were injected daily, beginning 5 days before the unilateral ureteral ligation or sham operation and until 10 days after it. At 10 days after UUO, all rats were sacrificed with high-dose ketamine. Malondialdehyde, glutathione, nitric oxide (NO), and 8-hydroxydeoxyguanosine levels and inducible NO synthase (iNOS), p38-mitogen-activated protein kinase (p38-MAPK), and nuclear factor kappa B (NF-kB) expression were studied. Histopathological examination of the obstructed kidney was also performed. RESULTS UUO was accompanied by a significant increase in malondialdehyde, NO, and 8-hydroxydeoxyguanosine along with a significant decrease in glutathione levels in the kidney tissue, as well as a significant elevation in iNOS, p38-MAPK, and NF-kB expression. MLT treatment resulted in reduction of the parameters of oxidative stress and the iNOS, p38-MAPK, and NF-kB expression. MLT treatment also reduced the development of leukocyte infiltration and interstitial fibrosis in UUO rats. CONCLUSIONS MLT may prevent UUO-induced kidney damage in rats by reducing oxidative stress. The mechanism for this is likely mediated via reduction in the expression of iNOS, p38-MAPK, and NF-kB, since MLT reduces the activation of these pathways.

Protective Effect of a Potent Antioxidant, Pomegranate Juice, in the Kidney of Rats with Nephrolithiasis Induced by Ethylene Glycol

PURPOSE We aimed to study the protective effects of pomegranate juice (PJ) on ethylene glycol (EG)-induced crystal deposition in renal tubules, renal toxicity, and inducible nitric oxide synthase (iNOS) and nuclear factor-kappaB activities in rat kidneys. MATERIALS AND METHODS Fifty-six rats were divided into four equal groups: Control, EG, EG + 50 microL PJ/d (PJ50), and EG + 100 microL PJ/d (PJ100). Rats were sacrified on days 10 and 45. Tissue sections were evaluated under light and polarized microscopy for the presence and degree of crystal deposition and toxicity in the kidneys. Crude extracts of the cortex were used to determine reduced gluthatione (GSH), nitric oxide (NO), and malondialdehyde (MDA) levels. RESULTS In the EG group, crystal depositions were more evident and mild crystalization was observed in proximal tubules on day 10; severe crystalization and granulovacuolar epithelial cell degeneration were observed on day 45. There was limited or no crystal formation in the EG + PJ-given groups. There were completely normal renal and tubular structures in the control group. There was no significant difference between the four groups in serum levels of sodium, potassium, blood urea nitrogen, and creatinine in any sampling time. Hyperoxaluria, a marked increase in MDA and NO levels, and decrease of GSH were observed in the EG-given groups compared with the others. There were marked iNOS and p65 expressions in only the EG-given rats compared with control and PJ groups, immunohistochemically. CONCLUSION This experiment shows the protective effect of PJ in the EG-induced crystal depositions in renal tubules.

The role of adrenomedullin in varicocele and impotence.

Objective To assess the levels of adrenomedullin (a vasodilatory peptide) in penile blood before and after injection with papaverine in impotent men, and in the internal spermatic vein in infertile patients with varicocele, comparing the results with levels in the brachial vein in the same patients.

Protective Effect of Montelukast Which Is Cysteinyl-Leukotriene Receptor Antagonist on Gentamicin-Induced Nephrotoxicity and Oxidative Damage in Rat Kidney

Nephrotoxicity is a major complication of gentamicin (GEN). We aimed to evaluate the potential protective effect of montelukast (MK) against GEN-induced nephrotoxicity in rats. Thirty-two rats were randomly divided into four groups, each consisting of eight animals as follows: (1) the rats were control; (2) intraperitoneally injected with GEN 14 consecutive days (100 mg/kg/day); (3) treated with GEN plus distilled water via nasogastric gavage for 14 days; and (4) treated with GEN plus MK (10 mg/kg/day) for 14 days. After 15 days, rats were killed and their kidneys were taken and blood analysis was performed. Twenty-four hours urine collections were obtained in standard metabolic cages a day before the rats were killed. Tubular necrosis and interstitial fibrosis scoring were determined histopathologically in a part of kidneys; nitric oxide (NO), malondialdehyde (MDA), and reduced glutathione (GSH) levels were determined in the other part of kidneys. Statistical analyses were made by the chi-square test and analysis of variance. Serum urea and creatinine levels were significantly higher in rats treated with GEN alone, than the rats in control and GEN + MK groups.The GSH levels in renal tissue of only GEN-treated rats were significantly lower than those in control group, and administration of MK to GEN-treated rats significantly increased the level of GSH. The group that was given GEN and MK had significantly lower MDA and NO levels in kidney cortex tissue than those that was given GEN alone. In rats treated with GEN + MK, despite the presence of mild tubular degeneration and tubular necrosis are less severe, and glomeruli maintained a better morphology when compared with GEN group. We can say that MK prevents kidney damage with antioxidant effect, independently of NO.