Necip Ilhan

The changes of trace elements, malondialdehyde levels and superoxide dismutase activities in pregnancy with or without preeclampsia.

OBJECTIVES Increased free radical activity and lipid peroxidation may be implicated in the pathogenesis of preeclampsia. This study was initiated to assess antioxidant enzyme and trace metalss status in preeclampsia. DESIGN AND METHODS The comparison was made between the pregnant women with or without preeclampsia and healthy controls in this study. Samples were obtained from 24 normal nonpregnant (controls), 30 normal pregnant and 21 preeclamptic women in the third trimester. Lipid peroxidation end product, malondialdehyde (MDA), free radical scavenging enzyme activity, superoxide dismutase (SOD) and serum zinc (Zn), copper (Cu) levels were measured in either plasma/serum or erythrocytes of patients. Data were analyzed statistically using Students t-test. RESULTS In the preeclamptic group malondialdehyde, Cu levels were significantly increased, while Zn and SOD levels were significantly decreased compared to normal control group and healthy pregnant women. CONCLUSIONS Our findings give support that radical scavenging SOD is consumed by the increased lipid peroxidation in preeclampsia. This data may indicate an involvement of free radicals in the pathophysiology of preeclampsia. This study suggests a relationship between increased MDA, Cu levels and decreased SOD, Zn levels in pregnancy and preeclampsia.

Seminal plasma cytokine levels in the diagnosis of chronic pelvic pain syndrome

Abstract Background: Chronic non‐bacterial prostatitis/chronic pelvic pain syndrome (CPPS) are frequently encountered clinical entities characterized by painful and irritative voiding symptoms often referable to the prostate. Diagnosis usually depends on the symptoms and treatment mainly consists of reassurance, anti‐inflammatory medications and antibiotics in the absence of a documented infection. To have objective diagnostic criteria, we determined the possible roles and diagnostic efficacies of soluble cytokines interleukin‐1β (IL‐1β), tumor necrosis factor‐α (TNF‐α), IL‐2R, IL‐6 and IL‐8 in the seminal plasma of patients with different forms of CPPS.

A comparison of leptin and ghrelin levels in plasma and saliva of young healthy subjects

In the last 10 years, saliva has been increasingly used as a diagnostic fluid and in predictions of disease progression. Leptin and ghrelin are synthesized in several tissues including the salivary glands. The action of ghrelin is antagonistic to that of leptin. This study was undertaken to measure and compare the saliva ghrelin-leptin and plasma ghrelin-leptin levels in healthy young subjects. In 30 healthy subjects, after an overnight fast, saliva and plasma leptin levels were measured using the ELISA method while saliva and plasma immunoreactive ghrelin levels were measured using a commercial radioimmunoassay (RIA). The latter uses 125I-labeled bioactive ghrelin as a tracer and a rabbit polyclonal antibody raised against full-length octanoylated human ghrelin (Phoenix, Europe, Karlsruhe, Germany). The results of this investigation revealed that saliva leptin levels (6.19+/-2.10 microg/l) were lower than plasma levels (7.39+/-3.23 microg/l) while saliva ghrelin levels (188.5+/-84.7 pg/ml) were higher than plasma levels (126.4+/-38.5 pg/ml), when male and female subjects were considered together. Saliva leptin levels (5.93+/-1.94 microg/l) were lower than plasma levels (6.22+/-2.92 pg/ml) while saliva ghrelin levels (190.3+/-80.2 pg/ml) were higher than plasma levels (120.4+/-35.7 pg/ml) in young males. Saliva leptin levels (6.47+/-2.29 microg/l) were lower than plasma levels (8.73+/-3.14 microg/l) while saliva ghrelin levels (183.2+/-90.2 pg/ml) were higher than plasma levels (129.3+/-42.8 pg/ml) in young females, and both saliva and plasma leptin levels were slightly lower in male subjects in comparison with female subjects. Also, Immunohistochemistry study indicated that ghrelin positivity was found in ductus epithelium of salivary gland. We have demonstrated for the first time that saliva ghrelin levels were higher than in plasma while saliva leptin levels were almost the same as in plasma. Measurements of ghrelin and leptin in saliva is non-invasive, simple, and generally much preferred by patients and thus may be an acceptable alternative to plasma sampling.

The association between intima media thickness, central obesity and diastolic blood pressure in obese and owerweight children: A cross-sectional school-based study

OBJECTIVE To examine relationship between carotid intima-media thickness (IMT) and central obesity, cardiovasculary risk factors, and chronic inflammation markers in overweight and obese schoolchildren in Eastern Turkey. METHODS A cross-sectional school-based survey on 2765 schoolchildren was performed. We collected the clinical data (age, sex, percentage of body fat, and measured systolic blood pressure [BP] and diastolic BP, triglycerides, high- and low-density lipoprotein cholesterol, glucose, insulin, homocysteine and high-sensitivity C-reactive protein) in 67 obese and 24 overweight children. The control group was composed of nonobese children of similar age and sex. RESULTS Mean systolic and diastolic BP values in the cases of overweight and obese groups were higher than those in the control group cases (p=0.001). Obese and overweight children demonstrated a significantly thicker intima media as compared with the control group (p=0.001). Carotid IMT was significantly correlated to the body mass index (r=0.396, p=0.001), fat mass percentage (r=0.257, p=0.036), waist circumference (r=0.390, p=0.001), diastolic BP (r=0.266, p=0.030), glucose (r=0.250, p=0.042), and high-sensitivity C-reactive protein levels (r=0.269, p=0.001) in the obese group. In multiple linear regression analysis, carotid IMT correlated significantly to waist circumference (p=0.045), and diastolic BP (p=0.031) in obese group. CONCLUSIONS Obesity is related to cardiovascular risk factors leading to early atherosclerosis in schoolchildren. There is a relationship between atherosclerosis, and central obesity, diastolic BP, and chronic inflammation. Waist circumference measurement is more sensitive than other anthropometric measurements in predicting obesity and associated complications.

A Tomato Lycopene Complex Protects the Kidney From Cisplatin-Induced Injury via Affecting Oxidative Stress as Well as Bax, Bcl-2, and HSPs Expression

Cisplatin-induced nephrotoxicity is related to an increase in oxidative stress in the kidney. Lycopene, a carotenoid found in tomatoes, is a potent dietary antioxidant. In the present study, we investigated the effect of the tomato lycopene complex against cisplatin-induced lipid peroxidation and nephrotoxicity in rats. Male Wistar rats (n = 28, 8 wk old, between 200–215 g) were divided into 4 groups: (a) control, (b) tomato lycopene complex (6 mg/kg, daily; consisting of 6% lycopene, 1.5% tocopherols, 1% phytoene and phytofluene, and 0.2% β-carotene), (c) cisplatin (7 mg/kg i.p., single dose), and (d) cisplatin + tomato lycopene complex. Cisplatin administration increased serum urea-N (171 vs. 37 mg/dl) and creatinine (1.80 vs. 0.42 mg/dl) and decreased body weight in comparison with the control rats (P < 0.001). Serum creatinine and urea-N levels were lower in rats treated with tomato lycopene complex + cisplatin compared with rats treated with cisplatin alone (P < 0.001). The renal tissue from the cisplatin-treated rats had greater malondialdehyde (MDA; 172 vs. 93 nmol/g) and 8-isoprostane levels (1810 vs. 610 pg/g) than that from the control rats (P < 0.001). Tomato lycopene complex prevented the rise of MDA and 8-isoprostane (P < 0.001). No measurable lycopene could be detected in the serum of the control and cisplatin-treated rats, whereas lycopene was observed in the serum of rats supplemented with tomato lycopene complex. Renal Bax protein expression was significantly higher in the cisplatin-treated rats than in the control rats, and tomato lycopene complex treatment significantly reduced Bax expression (P < 0.001). The expression of Bcl-2 was higher in tomato lycopene complex/cisplatin-treated rats than in the cisplatin-injected rats (P < 0.05). The expression of renal HSP60 and HSP70 was significantly lower in tomato lycopene complex + cisplatin-treated rats than in rats treated with cisplatin alone (P < 0.001). These results suggest that tomato lycopene complex has protective effects against cisplatin-induced nephrotoxicity and lipid peroxidation in rats.

Regulation of renal organic anion and cation transporters by thymoquinone in cisplatin induced kidney injury.

In previous studies, we have demonstrated the biological activity of thymoquinone (TQ), an active compound extracted from the Nigella sativa plant, against cisplatin-induced neurotoxicity. Recenty, it was observed that there is an inherent lack in regulation of renal organic anion and cation transporters in cisplatin-induced nephrotoxicity. Here, we report, for the first time, the effect of TQ on alterations in the renal expression of organic anion transporters (OATs) and organic cation transporters (OCTs), as well as multidrug resistance-associated proteins (MRPs) in rats treated with cisplatin. Twenty-eight 8-week-old male Wistar rats were divided into four groups of control, TQ treated (10 mg/kg b.w. in drinking water for 5 days), cisplatin (7 mg/kg b.w., i.p.) and TQ and cisplatin combination treatment. Cisplatin-induced malondialdehyde (MDA) and 8-isoprostane increase was found to be markedly reduced in rats treated with TQ. In cisplatin only treated rats, the induced renal injury increased protein levels of the efflux transporters MRP2 and MRP4 while expression of OAT1, OAT3, OCT1 and OCT2 was reduced. In combination TQ- and cisplatin-treated rats, expression of MRP2 and MRP4 proteins was decreased in the kidneys. Conversely, TQ treatment increased levels of OCT1, OCT2, OAT1 and OAT3 and decreased levels of 8-isoprostane and MDA levels in cisplatin-treated rats. In conclusion, the present study shows that the TQ synergizes with its nephroprotective effect against cisplatin-induced acute kidney injury in rats.

The renoprotective effect of curcumin in cisplatin-induced nephrotoxicity

Abstract The polyphenol curcumin has several pharmacological effects, including antioxidant, anti-inflammatory and anti-cancer features. In this study, we evaluated the effects of curcumin in cisplatin-induced nephrotoxicity in rats. Male Wistar rats were divided into four groups: (1) control; (2) cisplatin (7 mg/kg body weight, intraperitoneal as a single dose); (3) curcumin (100 mg/kg via gavage, for 10 days); and (4) cisplatin and curcumin. The cisplatin-treated rats exhibited kidney injury manifested by increased serum urea and creatinine (p < 0.05). The kidney tissue from the cisplatin treated rats also exhibited a significant increase in the malondialdehyde (MDA) levels (p < 0.05). The treatment with curcumin prevented a rise in the serum urea, creatinine and MDA levels when compared to the control group kidneys (p < 0.05). The analysis the nicotinamide phosphoribosyltransferase (NAMPT) and sirtuin (SIRT) proteins (SIRT1, SIRT3 and SIRT4), which play important roles in the resistance to stress and the modulation of the threshold of cell death, showed similar trends (p < 0.05). In the cisplatin-only treated rats, the induced renal injury decreased the levels of the NAMPT and SIRT proteins. Conversely, the curcumin increased the levels of the NAMPT and SIRT proteins in the cisplatin-treated rats (p < 0.05). These data suggest that curcumin can potentially be used to reduce chemotherapy-induced nephrotoxicity, thereby enhancing the therapeutic window of cisplatin.

Effects of melatonin on carbon tetrachloride-induced changes in rat serum

Carbon tetrachloride (CCl4) is a volatile organic chemical, which causes tissue damage, especially to the liver and kidney. In experimental animals it has been shown to be carcinogenic. This study was designed to evaluate the effects of exogenous melatonin administration on the CCl4-induced changes of some biochemical parameters in rat blood. Twenty-four male Wistar rats were randomly divided into three equal groups: Control, CCl4 and CCl4 plus melatonin (CCl4+MEL). Rats in CCl4 group were injected subcutaneously with CCl4 0.5 ml/kg in olive oil while rats in CCl4+MEL group were injected with CCl4 (0.5 ml/kg) plus melatonin (25 mg/kg in 10% ethanol) every other day for one month. Control rats were treated with olive oil. Serum urea, creatinine, total protein, albumin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), total and conjugated bilirubin, alkaline phosphatase (ALP), gamma-glutamyl transferase (γ-GT), total iron, and magnesium levels were determined. Serum AST, ALT, total and conjugated bilirubin, ALP, γ-GT, and total iron levels were significantly higher in CCl4-treated rats than in the controls, while urea, total protein, and albumin levels were significantly lower. Melatonin treatment did not cause a significantly change in serum urea, total protein, and albumin levels. However, the elevations in AST, ALT, total and conjugated bilirubin, ALP, γ-GT, and total iron levels induced by CCl4 injections were significantly reduced by melatonin. On the other hand, melatonin administration significantly decreased serum magnesium levels. These results indicate that melatonin could be a protective agent against the CCl4 toxicity in rats, most likely through its antioxidant and free radical scavenger effects.ResumenEl tetracloruro de carbono (CCl4) es un agente cancerígeno que causa daños orgánicos, especialmente en hígado y riñón. En este trabajo se evalúan los efectos de la administración de melatonina sobre los cambios inducidos por CCl4 de algunos parámetros bioquímicos en suero de rata. Para ello, 24 ratas Wistar macho se dividieron en tres grupos (n=8): Control, CCl4 y CCl4 más melatonina (CCl4+MEL). A las ratas del grupo CCl4 se les inyectó diariamente CCl4 (0,5 ml/kg, sc en aceite de oliva) durante un mes y a las ratas CCl4+MEL se les inyectó además melatonina (25 mg/kg, sc en etanol al 10%) en días alterno. Las ratas control recibieron sólo aceite de oliva por vía subcutánea. Al final del tratamiento, se determinaron los niveles séricos de urea, creatinina, proteína total, albúmina, aspartato aminotransferasa (AST), alanina aminotransferasa (ALT), bilirrubina total y conjugada, fosfatasa alcalina (ALP), gamma-glutamil transpeptidasa (γ-GT), hierro total y magnesio. Los valores de AST, ALT, bilirrubina total y conjugada, ALP, γ-GT, y de hierro total fueron significativamente mayores en suero de ratas tratadas con CCl4 que en los controles, mientras que los niveles de urea, proteína total, albúmina fueron significativamente menores. El tratamiento de melatonina no modificó significativamente los cambios en la urea, proteína total y albúmina sérica. Sin embargo, los increamentos en los niveles de AST, ALT, bilirrubina total y conjugada, ALP, γ-GT y hierro total en suero inducidos por CCl4 se redujeron significativamente por la hormona. Además, la administración de melatonina provocó disminución de los niveles de magnesio. Los resultados indican que la melatonina puede ser un protector contra la intoxicación por CCl4 en ratas, probablemente por sus efectos antioxidantes.

Hepatotoxic activity of toluene inhalation and protective role of melatonin

This study was designed to investigate the harmful effects of toluene inhalation in the liver of rats and possible protective effects of melatonin on these detrimental effects. For this purpose, 21 adult male Wistar-albino rats were randomly divided into three equal groups. Animals in group I were used as control. The rats in group II were exposed to toluene (3000 ppm/1 hour/day) for 4 weeks, while the rats in group III were treated with melatonin (10 mg/kg/day, intraperitoneally [ip]) plus toluene inhalation. At the end of the experimental period, liver and blood samples were taken from the decapitated animals. Serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), total bilirubin and albumin levels were determined. Liver tissue sections were stained with routine histological methods and examined under the light microscope. In addition, the sections were immunohistochemically stained using avidin-biotin-peroxidase method for determination of apoptosis. The liver tissue activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT) and malondialdehyde (MDA) levels were also measured. Toluene inhalation significantly increased serum ALT, AST and tissue MDA, and decreased serum albumin, but did not affect serum ALP, total bilirubin levels and tissue SOD, GSH-Px and CAT activity when compared with controls. The increases in tissue MDA and serum ALT and AST levels induced by toluene inhalation were significantly inhibited by melatonin treatment. In light microscopic observations of tissues from toluene-inhaled rats, massive hepatocyte degeneration, ballooning degeneration and mild pericentral fibrosis were observed. Bax immune reactivity was also increased significantly. Melatonin treatment decreased the balloon degeneration, fibrosis and Bax immune reactivity in the liver of toluene-inhaled rats. In view of the present findings, it is suggested that melatonin has hepatoprotective effects against toluene toxicity via primarily antioxidative properties.

Orally Administered Lycopene Attenuates Diethylnitrosamine-Induced Hepatocarcinogenesis in Rats by Modulating Nrf-2/HO-1 and Akt/mTOR Pathways

Hepatocarcinogenesis is one of the most prevalent and lethal cancers. We studied the mechanisms underlying the inhibition of diethylnitrosamine (DEN)-induced hepatocarcinogenesis by lycopene in rats. Hepatocarcinogenesis was induced by an intraperitoneal injection of DEN followed by promotion with phenobarbital for 24 successive wk. The rats were given lycopene (20 mg/kg body weight) 3 times a week orally for 4 wk prior to initiation, and the treatment was continued for 24 consecutive wk. Lycopene reduced incidence, number, size, and volume of hepatic nodules. Serum alanine transaminase, aspartate aminotransferase, total bilirubin, and malondialdehyde (MDA) considerably increased and hepatic antioxidant enzymes (catalase, superoxide dismutase, glutathione peroxidase) and glutathione decreased in DEN-treated rats when compared with the control group. Lycopene significantly reversed these biochemical changes and increased the expression of NF-E-2-related factor-2)/heme oxygenase-1, and it decreased NF-κB/cyclooxygenase-2, inhibiting the inflammatory cascade and activating antioxidant signaling (P < 0.05). Lycopene also decreased DEN-induced increases in phosphorylated mammalian target of rapamycin (p-mTOR), phosphorylated p70 ribosomal protein S6 kinase 1, phosphorylated 4E-binding protein 1, and protein kinase B (P < 0.05). Lycopene is an active chemopreventive agent that offers protection against DEN-induced hepatocarcinogenesis by inhibiting NF-κB and mTOR pathways.