Alteration of gene expression profile in mouse embryonic stem cells and neural differentiation deficits by ethephon.

Ethephon, a member of the organophosphorus compounds, is one of the most widely used plant growth regulators for artificial ripening. Although million pounds of this chemical is being used annually, the knowledge regarding its molecular toxicity is yet not sufficient. The purpose of this study was to evaluate the potential developmental toxicity of ethephon using embryonic stem cell model. The mouse embryonic stem cells (mESCs) were exposed to various concentrations of ethephon and the viability, cell cycle alteration and changes in the gene expression profile were evaluated using high-throughput RNA sequencing. Further, the effect of ethephon on neural differentiation potential was examined. The results showed that ethephon at noncytotoxic doses induced cell cycle arrest in mESCs. Gene ontology enrichment analysis showed that terms related to cell fate and organismal development, including neuron fate commitment, embryo development and cardiac cell differentiation, were markedly enriched in ethephon-treated cells. Neural induction of mESCs in the presence of ethephon was inhibited and the expression of neural genes was decreased in differentiated cells. Results obtained from this work clearly demonstrate that ethephon affects the gene expression profile of undifferentiated mESCs and prevents neural differentiation. Therefore, more caution against the frequent application of ethephon is advised.

Evaluation of oxidative stress and antioxidant parameters in children with carbon monoxide poisoning.

OBJECTIVE: In this study, we aimed to investigate oxidative stress and antioxidant parameter levels in patients with carbon monoxide (CO) poisoning. METHODS: The study was conducted prospectively between March 1, 2015 and April 30, 2016 in the pediatric emergency department. Eligible patients included children aged 0-18 years old with a diagnosis of CO poisoning. To determination of oxidative stress and antioxidant parameter levels, venous blood with heparinized and urine samples were drawn during the admission and after normobaric oxygen (NBO) and hyperbaric oxygen (HBO) treatment. RESULTS: Forty-seven children with CO poisoning for study group and 29 patients as control group were included to the study. Sixteen patients treated with HBO. Basal plasma malondialdehyde levels were found to be significantly higher in the CO poisoning group when compared with the control group (p = 0.019). There is no significant difference in oxidative stress and antioxidant parameter levels except erythrocyte catalase enzyme levels in patients treated with NBO when comparing before and after NBO treatment (p > 0.05). Decreasing of basal erythrocyte catalase enzyme levels were found statistically significant after NBO treatment (p = 0.04). There was no significant difference in oxidative stress and antioxidant parameter levels in patients treated with HBO before and after therapy (p > 0.05). CONCLUSIONS: CO poisoning is associated with increased lipid peroxidation in children immediately after the poisoning. However, both treatment modalities including NBO or HBO do not have a significant effect on oxidative stress or antioxidant parameter levels.

Evaluation of oxidative and antioxidative parameters in pediatric hematopoietic SCT patients.

Conditioning regimens preceding hematopoietic SCT (HSCT) usually consist of high-dose chemotherapy. Chemotherapy and radiation therapy are associated with increased formation of free radicals and depletion of critical plasma and tissue antioxidants. Oxidative stress and antioxidant depletion have been described during the transplantation period in HSCT patients. In a limited number of studies, it was observed that the conditioning regimen resulted in oxidative stress and antioxidant depletion in HSCT patients. The objective of this study was to look for further evidence of oxidative stress and antioxidant status in pediatric HSCT patients. In this study, blood samples were collected from 21 pediatric allo-HSCT patients before and after conditioning therapy. Erythrocyte and plasma malondialdehyde (MDA) levels, erythrocyte reduced and oxidized glutathione (GSH) levels, erythrocyte antioxidant enzymes activities, plasma α-tocopherol and ß-carotene levels were determined. After high-dose chemotherapy, erythrocyte and plasma MDA levels increased. Reduced GSH levels decreased whereas oxidized GSH levels increased first and then decreased significantly compared with the values before the chemotherapy regimen. It was also observed that catalase, superoxide dismutase and GSH-S-transferase activities decreased, but there was no change in GSH peroxidase activity. On the other hand, plasma α-tocopherol levels increased, but ß-carotene levels did not change.

Hypocholesterolemia is associated negatively with hemolysate lipid peroxidation in sickle cell anemia patients.

The oxidative stress levels in plasma and hemolysate and cholesterol levels in plasma of sickle cell anemia patients, carriers and controls were evaluated. A total of 40 cases-17 patients, 13 carriers and 10 controls-were involved in the study. Plasma and hemolysate malondialdehyde (MDA) were detected via thiobarbituric acid reaction with a fluorimetric detector by high-performance liquid chromatography system. Plasma cholesterol was determined by enzymatic colorimetric method. Mean MDA levels of SCA patients were higher than those of the carriers' and healthy children's both in plasma and in hemolysate (P < 0.005). The mean plasma and hemolysate MDA levels were 25.3 ± 1.6 nmol/l and 86.7 ± 19.3 nmol/l in patients, 19.1 ± 0.8 nmol/l and 54.1 ± 10.8 nmol/l in carriers and 19.6 ± 0.8 nmol/l and 56.8 ± 9.3 nmol/l in healthy children. Mean plasma total cholesterol levels were 92.1 ± 19.1 mg/dl in patients, 116.2 ± 23.3 mg/dl in carriers and 126.6 ± 16.4 mg/dl in controls (P < 0.005). There was a significant negative correlation of -0.520 between hemolysate MDA and plasma cholesterol levels in patients (P < 0.05). The degree of correlation increased up to -0.782 (P = 0.008) in the patients with HbSS phenotype. This negative correlation between MDA and cholesterol may imply a potential association between oxidative stress and hypocholesterolemia in sickle cell anemia.

Ochratoxin A: is it present in breast milk samples obtained from mothers from Ankara, Turkey?

Breast feeding is very important in the first year of life. However, breast milk may be contaminated with many residues of xenobiotics and naturally occurring toxins such as mycotoxins. Ochratoxin A (OTA) is one of mycotoxins that may play a causative role in some diseases seen in neonates. Therefore, the present study was undertaken to determine OTA levels in breast milk samples. For this purpose breast milk samples were collected from 75 mothers. Their babies were in-patients in the Department of Pediatrics, Section of Neonatology, Hacettepe University, Faculty of Medicine, in Ankara, Turkey. All samples were stored at -20 degrees C until analysis. Following an extraction procedure, OTA levels were determined by high-performance liquid chromatography (HPLC). Mean coefficient values for within-day and between-day variations of the method were 7.3 and 4.9%, respectively. The detection limit of the method was found to be 10 ng l(-1). The recovery percentage of OTA was 91.70 and 136.6 for two different concentrations added to breast milk samples. OTA was found in all samples tested in the range of 620.87-13111.30 ng l(-1). Considering potential hazard of OTA to human health, and especially the vulnerability of infants, the present data suggest the necessity of further research on OTA in Turkey, either monitoring its levels in biological fluids and foods or evolving protection strategies.

Exposure of newborns to aflatoxin M1 and B1 from mothers' breast milk in Ankara, Turkey.

Aflatoxins (AFs) are important risks for human health due to their widespread presence in foods and environment. However, contamination risk of breast milk with different pollutants including AFs is high in today's life conditions. Since breast milk is a major nutrient for infants, feeding of infants with safe milk is essential. Therefore, the objective of this study was to determine the levels of AF M(1) and B(1) in breast milk samples collected from 75 mothers in Ankara, Turkey. AF M(1) and B(1) levels were investigated by high performance liquid chromatography (HPLC) with a fluorescence detector following an extraction procedure. The limit of detection was found to be 5 ng/l. Both AFs were detected in diverse degrees in all breast milk samples: The level of AF M(1) were in the ranges of 60.90-299.99 ng/l, and AF B(1) were in the ranges of 94.50-4123.80 ng/l. These results pointed out the exposure of mothers and neonates to AF M(1) and B(1), and the necessity of further research on mycotoxin contamination both in foods and biological fluids as well as protection strategies.