Nurten Özçelik

Ochratoxin A in human serum samples collected in Isparta-Turkey from healthy individuals and individuals suffering from different urinary disorders

Ochratoxin A (OA) is a nephrotoxic fungal metabolite (mycotoxin) occurring in foodstuffs. The compound is causally associated with mycotoxin porcine nephropathy, a disease comparable with a human kidney disease called endemic nephropathy. In this paper OA levels in the human serum samples collected from healthy individuals and individuals suffering from different urinary disorders in Isparta-Turkey are presented. OA was measured in serum samples of 40 healthy people and a total of 93 patients with different kinds of urinary disorders. Four different kinds of urinary disorders were represented: chronic renal failure treated by hemodialysis (35), chronic renal failure treated by peritoneal dialysis (28), patients with bladder cancer (15), patients with renal stones (15). Analysis of OA in human blood samples was performed using an analytical method based on the measurement of fluorescence spectra. The mean concentration of OA in the healthy group was 0.4 +/- 0.28 ng/ml. The highest mean concentration was found in the group of patients treated by hemodialysis, 2.1+/- 1.2 ng/ml. The mean concentrations of the toxin in all patients groups were higher compared to the control group. Also, a significant difference was found between the mean concentrations of the groups of patients treated by dialysis (hemodialysis or peritoneal dialysis) and of the patients with renal stones or bladder cancer, only with the exception of the difference between peritoneal dialysis and renal stones group. No other significant differences were found when comparing the two groups. The findings indicate that OA may have a role in the human urinary pathology considered herein. A higher level of OA in dialysis groups compared to the control, renal stones and bladder cancer groups could probably be explained by the reduced glomerular filtration rate of these patients.

Cytogenetic abnormalities detected in patients with non-obstructive azoospermia and severe oligozoospermia.

PurposeTo find the frequency and types of major chromosomal abnormalities with nonobstructive azoospermia and severe oligozoospermia to give appropriate genetic counseling before assisted reproduction techniques in Isparta (South of Turkey), and to investigate the general characteristics in this infertile male population.Methods and patientsA total of 115 infertile males (92 were azoospermic, 23 severe oligospermic) were studied for the cytogenetic evaluation prior to use of assisted reproduction techniques. Also, 60 fertile males as a control group were studied. Karyotyping was performed on peripheral blood lymphocytes according to the standard methods. Levels of luteinising hormone, follicle-stimulating hormone (FSH), testosterone and prolactin were obtained and a testicular sonography examination was conducted.ResultsThe total prevalence of chromosomal abnormalities was found to be 4.3% (5/115), including 4 patients with Klinefelter’s Syndrome and 1 patient with gonadal dysygenesis (46XX). All of them were azoospermic males, corresponding to a frequency of 5.4% (5/92 patients). Oligozoospermic males and control males had no chromosomal abnormalities. There was a significant difference in serum FSH, LH, mean testicular volume and smoking when comparing patients (both azoospermic and oligozoospermic) and control groups (p < 0.05). Also, there was a significant difference in serum FSH, LH and mean testicular volume when compared with azoospermic and oligozoospermic patients (p < 0.05)ConclusionsThe occurrence of chromosomal abnormalities among infertile males strongly suggests the need for routine genetic testing and counseling prior to the employment of assisted reproduction techniques.

The effects of ochratoxin A on lipid peroxidation and antioxidant enzymes: a protective role of melatonin

Various studies indicate that the mycotoxin ochratoxin A (OTA) is a carcinogenic, genotoxic, teratogenic, immunotoxic, and nephrotoxic agent. In the present study, the activities of some enzymes in the serum and liver of rats with ochratoxicosis and the effects of melatonin on these enzymes were investigated. Rats were divided into three equal groups, each consisting of eight rats; control, OTA (289 μg/kg per day) and OTA + melatonin groups for this study. In the OTA treated group, the level of lipid peroxidation (LPO) and the activities of glutathione peroxidase (GSH-Px) were increased in the liver and serum in comparison with the control group. The activities of catalase (CAT) and superoxide dismutase (SOD) were significantly changed in the serum when compared with controls. Our results showed structural tissue damage in the liver in OTA-treated rats. Melatonin decreased the OTA-induced damage to support the antioxidant defense system and/or with free radical scavenger action.

Ameliorating role of Caffeic acid phenethyl ester (CAPE) against isoniazid- induced oxidative damage in red blood cells

Isoniazid (INH) still remains a first-line drug both for treatment and prophylaxis of tuberculosis, but various organs toxicity frequently develops in patients receiving this drug. We aimed to investigate possible toxic effects of INH on rat red blood cells (RBCs), and to elucidate whether Caffeic acid phenethyl ester (CAPE) prevents a possible toxic effect of INH. Experimental groups were designed as follows: control group, INH group, INH + CAPE group. Compared with the control, the INH caused a significant increase in superoxide dismutase (SOD) activity and malondialdehyde (MDA) levels, and a decrease in glutathione peroxidase (GSH-Px) and catalase (CAT), which are recently used to monitor the development and extent of damage due to oxidative stresses. CAPE administration to INH group ameliorated above changes due to INH.

The effects of isoniazid on hippocampal NMDA receptors: protective role of erdosteine.

Isoniazid (INH) has neurotoxic effects such as seizure, poor concentration, subtle reduction in memory, anxiety, depression and psychosis. INH-induced toxic effects are thought to be through increased oxidative stress, and these effects have been shown to be prevented by antioxidant therapies in various organs. Increased oxidative stress may be playing a role in these neurotoxic effects. N-methyl D-aspartat receptors (NMDA) are a member of the ionotropic group of glutamate receptors. These receptors are involved in a wide variety of processes in the central nervous system including synaptogenesis, synaptic plasticity, memory and learning. Erdosteine is a potent antioxidant and mucolytic agent. We aimed to investigate adverse effects of INH on rat hippocampal NMDAR receptors, and to elucidate whether erdosteine prevents possible adverse effects of INH. In the present study, compared to control group, NMDAR2A (NR2A) receptors were significantly decreased and malondialdehyde (MDA), end product of lipid peroxidation, production was significantly increased in INH-treated group. On the other hand, administration of erdosteine to INH-treated group significantly increased NR2A receptors and decreased MDA production. In conclusion, decreasing NR2A receptors in hippocampus and increasing lipid peroxidation correlates with the degree of oxidative effects of INH and erdosteine protects above effect of INH on NR2A receptors and membrane damage due to lipid peroxidation by its antioxidant properties.

Ochratoxin a reduces NMDA receptor subunits 2A and 2B concentrations in rat hippocampus: partial protective effect of melatonin:

Ochratoxin A (OTA) is a mycotoxin produced by several fungi. Many foods can be contaminated by OTA, which is consequently found in the blood of humans and animals. It is known that OTA accumulates in the brain. The aim of this study was to investigate the effects of OTA on the brain. For this purpose, the effect of OTA on N-methyl-Daspartate (NMDA) receptor subunits 2A (NR2A) and 2B (NR2B) in the hippocampus and the protective effect of melatonin were investigated. Three groups of eight rats were used: controls, OTA-treated rats (OTA dose 289 mg/ kg per day) and OTA-melatonin-treated rats (melatonin dose 10 mg/kg per day). After four weeks of treatment, electrophoretic examinations were performed using SDSpolyacrylamide gel electrophoresis and Western blotting of hippocampal homogenates of the different groups. The concentrations of NR2A and NR2B in the OTA group were significantly lower than in the control group. The concentration of NR2B was significantly increased when melatonin was co-administered with OTA compared with OTA only. There was also a significant increase in NR2A levels when melatonin was co-administered with OTA. As a result, subchronic administration of OTA reduced hippocampal NMDA receptor subunits 2A and 2B concentrations in rats. It was thought that this alteration might affect cognitive functions because hippocampal NMDA receptors are involved in the memory and learning processes. Melatonin exhibited a partially protective effect on NR2A and NR2B against OTA.

Anticlastogenic effect of caffeic acid phenethyl ester on cisplatin-induced chromosome aberrations in rat bone marrow cells.

Caffeic acid phenethyl ester (CAPE) is an antioxidant that can scavenge free radicals and protect cellular macromolecules, including DNA and proteins, from oxidative damage induced by various agents. The protective effect of CAPE on cisplatin-induced chromosome aberrations has been determined in rat bone marrow cells. The animals were pretreated with a single dose of CAPE (10 μmol/kg body weight [b.w.]) injected intraperitoneally (i.p.) 24 hours before the administration of cisplatin and then sacrificed 24 hours after the cisplatin administration. Cisplatin was administered to rats either alone (5 mg/kg b.w., i.p.) or after CAPE treatment. CAPE has led to a statistically significant decrease in the total number of chromosomal aberrations and abnormal metaphases induced by cisplatin when compared with only cisplatin given groups. We have concluded that CAPE could prevent cisplatin-induced chromosome aberrations by establishing a potent free radical scavenger effect.

Protective role of caffeic acid phenethyl ester and erdosteine on activities of purine-catabolizing enzymes and level of nitric oxide in red blood cells of isoniazid-administered rats*

The aim of this experimental study was to investigate the possible role of nitric oxide (NO) and the activities of adenosine deaminase (ADA) and xanthine oxidase (XO) in the pathogenesis of isoniazid (INH)-induced oxidative damage in red blood cells (RBCs), and also to show the effect of caffeic acid phenethyl ester (CAPE) and erdosteine, antioxidants, in decreasing this toxicity. A total of 25 adult male rats were divided into four experimental groups as follows: control group (n = 7), INH-treated group (n = 6), INH + CAPE–treated group (n = 6), and INH + erdosteine–treated group (n = 6). INH, INH-CAPE, and INH-erdosteine–treated groups were treated orally with INH 50 mg/kg daily and with the tap water for 15 days. Control group was given only tap water. CAPE was intraperitoneally injected for 15 days at a dose of 10 μmol/kg. Erdosteine was treated orally for 15 days at a dose of 10 mg/kg/day. The injection of INH led to a significant increase in the activities of ADA, XO, and NO levels in RBCs of rats. Co-treatment with CAPE caused a significant decrease in the activities of ADA and XO and the levels of NO in RBCs. In addition, co-treatment with erdosteine caused a significant decrease in the activities of ADA and XO and the levels of NO in RBCs. The results of this study showed that ADA, XO, and NO may play an important role in the pathogenesis of INH-induced oxidative stress in RBCs. CAPE and erdosteine may have protective potential in this process and they may become a promising drug in the prevention of this undesired side effect of INH.

Cytogenetic Finding of Breast Cancer Cases and in Their First-Degree Relatives

Purpose The aim of this study was to evaluate and compare the rate of sister chromatid exchange (SCE), the occurrence of micronuclei, and the lymphocyte proliferation rate index (PRI) in patients with breast cancer, their first-degree relatives, and healthy volunteers. Methods We analyzed the frequency of SCE and micronuclei, and the PRI in the peripheral blood lymphocytes of 30 women with breast cancer, 22 of their female family members, and 20 age-matched healthy female volunteers. Results SCE occurred significantly more often in the lymphocytes of breast cancer patients (10.84±0.4 per metaphase), compared with their first-degree relatives (7.45±0.54) and controls (5.94±0.2) (p<0.001 for both). The mean SCE frequency was not statistically different between first-degree relatives and controls (p=0.071). Similarly, micronuclei occurred at a significantly higher rate in breast cancer patients (9.6±0.72), and in their first-degree relatives (7±0.64), compared to controls (3.85±0.4) (p<0.001 and p=0.001, respectively). There was also a significant difference between the occurrence of micronuclei in patients compared to their family members (p=0.021). The PRI was significantly lower in patients (1.61±0.1), compared with both their first-degree relatives (1.75±0.1), and controls (1.74±0.1) (p=0.001 and p=0.002, respectively). Conclusion Increased SCE and the occurrence of micronuclei, as well as a reduced PRI are associated with breast cancer. Furthermore, increased SCE and the frequency of micronuclei in a first-degree relative suggest that they exhibit greater genetic instability than women of the same age.

Novel GDAP1 Mutation in a Turkish Family with CMT2K (CMT2K with Novel GDAP1 Mutation)

Mutations in the ganglioside-induced differentiation-associated protein 1 gene (GDAP1) cause Charcot–Marie–Tooth type 2 (CMT2), a severe autosomal recessive form of neuropathy associated with axonal phenotypes. It has been screened in this study for the presence of mutations in the coding region of GDAP1, which maps to chromosome 8q21, in a family with CMT2. To date, 29 mutations in the GDAP1 have been reported in patients of different ethnic origins. Here, we report a novel missense mutation (c.836A>G), and two polymorphisms: a silent variant (c.102G>C), and a 5′-splice site mutation (IVS5+24C>T) in GDPA1 gene identified in a five generation Turkish family with autosomal recessive CMT2.