Abdulmuttalip Simsek

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.

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.

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.

A single-nucleotide polymorphism in the matrix metalloproteinase-1 promoter enhances bladder cancer susceptibility.

To explore the association between the promoter polymorphism (that influences the transcriptional level) of matrix metalloproteinase‐1 (MMP‐1, associated with tumour cell invasion and metastasis) and bladder cancer in a Turkish population.

New Biomarkers for the Quick Detection of Acute Kidney Injury

Acute kidney injury (AKI) is a common and strong problem in the diagnosis of which based on measurement of BUN and serum creatinine. These traditional methods are not sensitive and specific for the diagnosis of AKI. AKI is associated with increased morbidity and mortality in critically ill patients and a quick detection is impossible with BUN and serum creatinine. A number of serum and urinary proteins have been identified that may messenger AKI prior to a rise in BUN and serum creatinine. New biomarkers of AKI, including NGAL, KIM-1, cystatin-C, IL-18, and L-FABP, are more favourable tests than creatinine which have been identified and studied in several experimental and clinical training. This paper will discuss some of these new biomarkers and their potential as useful signs of AKI. We searched the literature using PubMed and MEDLINE with acute kidney injury, urine, and serum new biomarkers and the articles were selected only from publication types in English.

Effects of Pomegranate Juice on Hyperoxaluria-Induced Oxidative Stress in the Rat Kidneys

To evaluate the role of the inducible nitric oxide synthase (iNOS), selective nuclear factor-kB (NF-kB), and p38-mitogene-activated protein kinase (p38-MAPK) on hyperoxaluria-induced oxidative stress and stone formation in rat kidneys. The rats were divided into five groups: group 1, control group; group 2: ethylene glycol (EG) group; group 3: EG + pomegranate juice (PJ)-low group; group 4: EG + PJ-middle group; group 5: EG + PJ-high group. Rats were sacrificed on 7, 15, and 45 days. The iNOS expression, p65-NF-kB and p38-MAPK activity, and oxidative stress markers were evaluated in the kidney. Crystal depositions were evident on day 7, and mild and severe crystallization were observed on day 15 and 45 in EG group, respectively. There was limited or no crystal formation in rats in both middle- and high-dose PJ groups when compared to low-dose PJ group. Crystal depositions, iNOS, p38-MAPK and p65-NF-kB activity, and oxidative stress markers were found to be decreased by middle- and high-dose PJ treatment. PJ was found to have inhibitory effects on renal tubular cell injury and oxidative stress caused by oxalate crystals by reducing ROS, iNOS, p38-MAPK, and NF-kB expression.

The effect of regular exercise on penile nitric oxide synthase expression in rats

Erectile dysfunction (ED) is a major public health problem that seriously affects the quality of life of patients and their partners and its prevalence increases significantly with ageing. In this study, we tested the hypothesis that age-associated decrease in penile endothelial (eNOS) and neuronal nitric oxide synthase (nNOS) activity in aged rats may be increased by regular exercise. A total of 28 young (4 m) and aged (24 m) male rats were divided into four equal groups: group 1 - young control; group 2 - young trained; group 3 - old control and group 4 - old trained group. Groups 2 and 4 rats were trained to swim for 30 min a day and 5 days a week, which lasted 8 weeks. At the end of 8 weeks, rats were sacrificed and penile tissues evaluated for eNOS and nNOS activities. eNOS and nNOS activities were evaluated by immunohistochemistry in paraffinized penile tissues and results assessed semiquantitatively. Results also were compared with healthy age-matched and adult (4 m) controls. Serum level of testosterone (T) was determined using ELISA kits (Beckman Coulter, Fullerton, CA, USA). In penile tissues of aged control rats, eNOS and nNOS staining were weakly positive; however in trained groups, eNOS and nNOS immunoreactivity were increased. In young control group, eNOS and nNOS activities were more intense than aged control. eNOS and nNOS activities were higher in adult trained group than control. Serum T concentrations were significantly higher in young and aged trained group than in control groups. We can suggest that regular exercise upregulates eNOS and nNOS expressions in the aged and young rat penis. Regular exercise may improve penile erection by increasing penile neurotransmitter in both young and aged rats.

Comparison of paroxetine and dapoxetine, a novel selective serotonin reuptake inhibitor in the treatment of premature ejaculation.

Dapoxetine hydrochloride is a selective serotonin reuptake inhibitor and the first drug approved for the on-demand treatment of premature ejaculation (PE). Our objective in this study was to characterize the efficacy of on-demand dapoxetine (30 and 60 mg) and daily paroxetine (20 mg) usage in treating PE. We conducted a 1 month study involving a total of 150 patients. Patients were divided into three groups of 50. Group 1 were treated with on-demand dapoxetine (30 mg), Group 2 with on-demand dapoxetine (60 mg) and Group 3 with daily paroxetine (20 mg). Our outcome measurement was increased from baseline intravaginal ejaculatory latency time (IELT) after treatment. The IELT increased from baseline to posttreatment by 117%, 117% and 170% in the paroxetine group (P < 0.01), 30 mg dapoxetine group (P < 0.01) and 60 mg dapoxetine group (P < 0.01), respectively. The increase from baseline IELT were similar for the 30 mg dapoxetine and paroxetine groups (P > 0.05), while the 60 mg dapoxetine group had a larger posttreatment IELT increase compared with the 30 mg dapoxetine (P < 0.05) and paroxetine (P < 0.01) groups. Dapoxetine (60 mg) 1–3 h before planned intercourse is a very effective treatment modality for PE. However, an on-demand dose of 30 mg dapoxetine is no more effective than the currently prescribed paroxetine treatment.