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The aim of this study was to investigate oxidative stress induced by perfluorooctanoic acid (PFOA) in the brain and liver tissues of Balb/c mice as well as protective effects of taurine and coenzyme Q10 (CoQ10) in both organs. For this purpose, animals were treated with PFOA (15 and 30 mg/kg) orally and their lipid peroxidation, total glutathione levels (GSH), and antioxidant enzyme activities measured and both tissues analysed for histopathological changes. Our results showed a dose-dependent decrease in body weight and increase in relative brain and liver weights, PFOA-induced lipid peroxidation and reduced glutathione peroxidase (GPx) activity in the brain tissue, and changes in GSH levels, GPx, superoxide dismutase (Cu-Zn SOD), and catalase (CAT) activities in the liver tissue. Pre-treatment with taurine or CoQ10 provided protection against PFOA-induced Cu-Zn SOD reduction in the liver tissue. Our findings evidence the depleting effect of PFOA on antioxidative systems and confirm that PFOA exerts its (neuro)toxicity through oxidative stress, but further research is needed to identify the exact toxicity mechanisms, especially in the brain., Cilj je ovog istraživanja bio utvrditi oksidacijski stres prouzročen perfluorooktanoičnom kiselinom (PFOA) u moždanom i jetrenom tkivu Balb/c miševa te zaštitno djelovanje taurina i koenzima Q10 (CoQ10) u oba organa. U tu su svrhu životinje izložene PFOA-i u oralnoj dozi od 15 ili 30 mg/kg tjelesne težine te su u oba tkiva analizirane histopatološke promjene i izmjerene lipidna peroksidacija, ukupne razine glutationa (GSH) i aktivnosti antioksidacijskih enzima. Naši rezultati pokazuju smanjenje ukupne tjelesne težine i povećanje relativne težine organa ovisne o dozi, lipidnu peroksidaciju i smanjenu aktivnost glutation peroksidaze (GPx) u moždanom tkivu te promjene razina GSH i aktivnosti GPx, superoksid dismutaze (Cu-Zn SOD) i katalaze (CAT) u jetrenom tkivu. Prethodna primjena taurina ili CoQ10 zaštitila je životinje izložene PFOA-i od pada razina Cu-Zn SOD u jetrenom tkivu. Naši rezultati potvrđuju da PFOA iscrpljuje antioksidacijske sustave i djeluje (neuro)toksično putem oksidacijskoga stresa, no potrebna su daljnja istraživanja kako bi se precizno utvrdili njegovi mehanizmi toksičnosti, napose u mozgu.

Objective: In this study, toxic effects of Roundup, one of the most common glyphosate-based herbicides (GBHs), were assessed on human bronchial epithelial cells (BEAS-2B). Material and Method: MTT and neutral red uptake assays were implemented for evaluation of cell viability at 24 and 48 h. Apoptosis detection was made by Muse analyzer while Hoechst staining was employed to detect apoptotic nuclear changes. In addition, dichlorofluorescein diacetate assay was used for the assessment of reactive oxygen species (ROS) formation. Result and Discussion: Similar half maximal inhibitory concentrations (IC50) were obtained from cytotoxicity assays. Results showed that significant reduction in the viability of BEAS-2B cells started to occur from 200 µM at 24 h and 50 µM at48 h treatment times. Roundup treatments for both time points were found to dose-dependently cause apoptosis and were also observed to induce cellular ROS formation. These findings suggest that GBHs can stimulate ROS production, as well as apoptosis on healthy human lung cells which is important considering inhalation is one of the primary exposure routes to these group of chemicals.

Perfluoroalkyl and polyfluoroalkyl substances (PFASs) draw considerable attention for their potential toxic effects in humans and environment. Drinking water is accepted as one of the major exposure pathways for PFASs. In this study, we measured concentrations of 10 perfluoroalkyl substances in 94 tap water samples collected in two different sampling periods (August 2017 and February 2018) from 33 provinces of Turkey, as well as in 26 different brands of plastic and glass-bottled water samples sold in supermarkets in Turkey. Perfluorohexanoic acid (PFHxA), perfluorobutane sulfonate (PFBS) and perfluoropentanoic acid (PFPeA) were the most frequently detected PFASs in the samples of tap waters. The maximum concentrations in tap waters were measured as 2.90, 2.37, 2.18, 2.04, and 1.93 ng/L, for PFHxA, perfluorooctanoic acid (PFOA), perfluorohexane sulfonate (PFHxS), perfluorooctane sulfonate (PFOS), and perfluorobutanoic acid (PFBA), respectively. The most abundant perfluorinated chemical in tap water samples was PFBA with 17%, followed by PFOS (13%), PFBS (12%), perfluoroheptanoic acid (PFHpA) (11%), PFHxA (11%), and PFOA (11%). The total PFASs concentration in tap water ranged from 0.08 to 11.27 ng/L. As regards bottled waters, the concentrations of PFASs were generally lower than those in tap water samples. These results revealed that tap water samples in Turkey might be considered generally safe based on the established guidelines around the world. However, due to their persistence and potential to accumulate and reach higher concentrations in the environment, careful monitoring of PFASs in all types of water is critical. (C) 2019 Elsevier Ltd. All rights reserved.

In the presence of ciprofloxacin (CPFX), free radical adduct formation was demonstrated in rat cerebral microsomes using a spin trap α-(4-pyridyl-1-oxide)-N-tert-butyl-nitrone by electron spin reso...

The aim of this study is to investigate the relationship between exposure to acute air pollution and meteorological factors on the frequency of epileptic attacks in children.This retrospective study was carried using patient files from a children's hospital in Diyarbakır, one of the largest cities in Turkey. In the present study, the possible relationship between epileptic attacks seen in children over a 10-year period, two air polluting factors (PMAccording to Model 2 and 3, the strongest relationship of the four Poisson Regression models, there was a significantly increased risk of pediatric emergency department admissions for seizures associated with a 10 µm/mMeteorological factors and air pollutants affect the number of pediatric patients admitted to the pediatric emergency department with epilepsy attacks.

© 2022 Elsevier B.V.Glyphosate-based herbicides (GBHs) are the most widely used herbicides all over the world and has gained more attention in recent years because of health safety concerns. In this study, Roundup, one of the most popular glyphosate formulations, was used to evaluate cytotoxic, oxidative stress and apoptosis inducing effects of GBHs in a human hepatocellular cell line (HepG2). Roundup was shown to significantly increase cellular reactive oxygen species (ROS) levels, which lead to activation of the nuclear factor-erythroid-2-related factor 2 (Nrf2) antioxidant defense pathway including reduced levels of heme oxygenase 1 (HO-1). Furthermore, Roundup was found to induce apoptosis and further analysis confirmed involvement of a mitochondrial-dependent pathway verified by increased Bax/Bcl-2 ratios. Investigation of the protective effects of antioxidants vitamin E (Vit E) and α-lipoic acid (LA) against Roundup toxicity showed that both antioxidants significantly reduced the cytotoxicity, ROS formation, HO-1 downregulation, and apoptosis and that Vit E did so more efficiently than LA. In conclusion, our findings highlight the ROS producing and apoptosis inducing effects associated with GBHs, the activation of Nrf2 pathway as a defense mechanism and the protective effects of Vit E and LA against GBH toxicity.

Objectives The aim of this descriptive study was to determine the sociodemographic characteristics of electronic (e)-cigarette users for clarifying the causes of e-cigarette smoking and to identify the carbon monoxide (CO) and urinary cotinine levels of the volunteers. Materials and methods Twenty volunteers who smoked e-cigarettes completed a questionnaire, and their exhaled CO and urinary cotinine levels were measured. An enzyme-linked immunosorbent assay kit was used for cotinine analysis. Results Overall, 85% of the participants were males, 60% were married, and 75% were college/university graduates. The median age of participants was 38.5 years. The participants' main reasons for starting to smoke were peer influence and curiosity. The participants' main reasons for smoking e-cigarettes were to quit and reduce smoking the conventional cigarettes and cost effectiveness. Only three people knew that smoking was harmful to health. The participants' CO levels were measured as a median of 3, lowest of 1, and highest of 22. Cotinine levels were "positive" in all samples. A moderate and statistically significant correlation was found between the amount of fluids used by the participants in 1 day (mL) and cotinine levels in urine specimens (Pearson correlation test, r=0.511, p=0.025). Conclusion The study is an important proof of the country's scientific work on e-cigarettes. Preventive strategies should be very strictly implemented for any tobacco products, including e-cigarettes, as they harm individuals and the community.

The electronic cigarette (e-cigarette), which is accepted as a new market by the tobacco industry, is highly dependent on health and is addictive due to its nicotine content. Informing and raising awareness is extremely valuable to protect the identified risks of e-cigarette in society. The aim of this study was to determine the socio-demographic characteristics of volunteer e-cigarette users, to determine the causes of e-cigarette smoking, to identify some risks (nicotine, carbon monoxide). In this descriptive study, volunteer electronic cigarette smokers participated in the questionnaire, carbon monoxide was measured, urine sample was taken and directed to the toxicology laboratory for measurement of cotinine, and cotinine was measured in urine. Twenty volunteer e-cigarette smokers participated in the survey. Eighty five percent of the participants were male, 60% were married, 75% were college / university graduates, 80% were working, 65% of them were economical, 35% were good, 40% and 35% regularly use medicines. The median age of participants was 38.5 years, the youngest participant was 22, the oldest was 69 years old. Fifteen (75%) of the respondents stated that they were passively affected by tobacco smoke. Eight of these 15 (73%) were exposed to friends, eight (54%) were at home, eight (54%) were at cafes, etc., and four were exposed at work. The participants' main reasons for starting to smoke are friend influence and curiosity. Thirty percent of participants had tried e-cigarette before using e-cigarette, 90% used e-cigarette every day, e-cigarette was most frequently obtained from internet and friends / relatives, 79% did not use cigarette e-cigarette and all use nicotine. Participants' median e-cigarette smoking duration was 5.5 months; monthly e-cigarette expenditures are median 60 TL. Participants main reasons to smoke e-cigarette are to quit smoking, reduce smoking cigarettes and for reasons of cheapness. Eleven of the respondents (55%) stated that they never smoked together with e-cigarette but 9 (45%) smoked together with e-cigarette, but e-cigarette smoking significantly reduced the cigarette. Only 15% of the participants (three people) knew that smoking was harmful to health; only 45% of e-cigarette users knew that e-cigarette is addictive although they all use nicotine in their e-cigarettes. Of the 19 people who responded to the question 15 (79%) do not consider leaving e-cigarettes. Participants' carbon monoxide levels were measured as median 3, lowest 1, highest 22. Carbon monoxide level in 25% of participants was found to be above 7 ppm, which is used as threshold value in determining smokers. The levels of cotinine detected in urine samples are 709.9, lowest 318.6, highest 825.3 ng / ml. A moderate and statistically significant correlation was found between the amount of fluids used by the participants in one day (ml) and cotinine levels in urine specimens (Pearson correlation test, r = 0.511, p = 0.025). As a result, this study, in which nicotine exposure and increase in carbon monoxide and urine cotinine levels due to the use of e-cigarettes is documented, is an important proof of the country's scientific work on e-cigarettes. Preventive strategies should be strictly used for any tobacco products including e-cigarettes. Funding Statement: This project was funded by Hacettepe University, Scientific Research Projects Coordination Unit (Project nb. TAY-2016-9469).

Toxic metals are one of the significant groups of chemical contaminants that humans are exposed to by oral, inhalation, and dermal routes. Exposure to these chemicals begins with intrauterine life and continues during lactation period at the first years of life. Breastfeeding has a much more special place than other nutrition options for infants. However, when possibility of contaminant transfer by breast milk is considered, its safety and quality is essential. Regarding infant and mother health and limited number of information on this field in Turkey, measuring contamination levels in breast milk is important. Therefore, in the present study, lead (Pb), cadmium (Cd), nickel (Ni), and arsenic (As) levels were measured by atomic absorption spectrometry in 64 breast milk samples obtained from mothers from Ankara, Turkey. Pb and Ni levels in breast milk samples were found to be 391.45 +/- 269.01 mu g/l and 43.94 +/- 33.82 mu g/l (mean +/- SD), respectively. Cd was found only in one of 64 samples, and the level was 4.62 mu g/l. As level was below the limit of quantification (LOQ, 7.6 mu g/l) in all samples. These findings will accurately direct strategies and solutions of protection against contaminants in order to reduce their levels in biological fluids.

The aim of this study was to investigate the possible time- and dose-dependent cytotoxic effects of cobalt chloride on Vero cells. The cultured cells were incubated with different concentrations of cobalt chloride ranging from 0.5 to 1,000 μM, and cytotoxicity was determined by 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide (MTT) and resazurin assays. Possible protective effects of vitamin E, coenzyme Q(10), and zinc chloride were also tested in this system. A gradual decrease in cell proliferation was observed at concentrations ~≥ 200 μM in incubation periods of 24, 48, 72, and 96 h with MTT assay. Exposure of cells to 500 and 1,000 μM cobalt chloride caused significant decrease in cell survival. A biphasic survival profile of cells was observed at 1-25 μM concentration range following 96 h of incubation. With resazurin assay, cytotoxicity profile of CoCl(2) was found comparable to the results of MTT assay, particularly at high concentrations and long incubation periods. Dose-dependent cytotoxicity was noted following exposure of cells to ≥ 250 μM of CoCl(2) for 24 h and ≥ 100 μM concentrations of CoCl(2) for 48-96 h. Pretreatment of cells with ZnCl(2) for 4 or 24 h provided significant protection against cobalt chloride-induced cytotoxicity when measured with MTT assay. However, vitamin E or coenzyme Q(10) was not protective. CoCl(2) had dose- and time-dependent cytotoxic effects in Vero cells. Preventive effect of ZnCl(2) against CoCl(2)-induced cytotoxicity should be considered in detail to define exact mechanism of toxicity in Vero cells.

In vitro and in vivo interactions which are commonly met during drug therapy and their toxicological outcomes are important. In order to increase effect of certain drugs, interactions, which are called as beneficial interactions, are intentionally applied. However, examples of these interactions are in limited number. On the other hand, untoward and hazardous interactions that cause very important outcomes in toxicological point of view are common. These types of interactions develop more easily during therapy with drugs have a narrow therapeutic window. Theophylline which is used in the treatment of asthma and chronic obstructive pulmonary disease (COPD) has also a narrow therapeutic window. Therefore, in the present review, some important examples resulted from interactions of theophylline with drug, diet, xenobiotic, herbal product, habits and their toxicological outcomes have been given.

The potential hazardous human exposure to aflatoxin M1 via consumption of milk and milk products has been demonstrated by several workers. Considering its risk to human health, determination of aflatoxin M1 levels in dairy products is important. Since there are limited data available on the occurrence of aflatoxin M1 levels in dairy products in Turkey, the aim of the present study was to investigate the presence of this toxin in various types of commonly consumed cheese and yogurt samples in the capital city of Turkey—Ankara. For this purpose, 39 samples of cheese and 40 samples of yogurt were randomly collected from supermarkets in Ankara. Aflatoxin M1 levels were determined by a competitive enzyme-linked immunosorbent assay (ELISA) kit. Aflatoxin M1 was detected in 11 cheese samples ranging from 78.20 to 188.44 ng/kg. Thirty-two of the 40 yogurt samples had aflatoxin M1 levels between 61.61 and 365.64 ng/kg. The results of this study indicated the importance of continuous surveillance of commonly consum...

Important role of milk in human, especially in infant nutrition is well known. On the other hand, contamination of milk with aflatoxins is considered as a potential risk for human health. The aim of this study was to determine the levels of aflatoxin M 1 in commonly consumed milk samples in Ankara, capital city of Turkey. Aflatoxin M 1 levels were investigated by high performance liquid chromatography (HPLC) with a fluorescence detector following sample clean-up using immunoaffinity columns. The mean recovery of the method was 117.9%. Standard curves were linear in the range of 10–200 ng/l with correlation coefficient of 0.9998. The limit of detection was found to be 10 ng/l. In this study, 27 milk samples were analysed. 24 of them were in categories of ultra high temperature treated, and 3 of them were daily-pasteurised milk. Aflatoxin M 1 was detected in 59.3% of all samples. However, only one sample among these was contaminated at a level above the maximum permissible limit (50 ng/l) accepted by European Union and Turkey for aflatoxin M 1 .

The aim of this study was to investigate the possible cytotoxic and apoptotic effects of a fluoroquinolone (FQ) antibiotic, ciprofloxacin (CPFX), on HeLa and HeLa-tat cell lines. The cultured cells were incubated with three different (20 to 100 mg/L) concentrations of CPFX, and cytotoxicity was determined by trypan blue test. A dose- and time-dependent decrease in cell proliferation was observed for both cell types except 50 to 100 mg/L CPFX for 24 h for HeLa-tat cells. CPFX-induced apoptosis was also measured by the acridin orange-ethidium bromide staining using a fluorescence microscope in both cell types. Our results showed an induction of apoptosis at 100 mg/L concentration of CPFX after 24 and 48 h of incubation in both cell types. These data confirmed our previous studies obtained with normal human fibroblast cell cultures and indicated that CPFX induces cytotoxicity and apoptosis in HeLa cells.

The possible oxidative stress inducing effect of a fluoroquinolone (FQ) antibiotic, ciprofloxacin (CPFX), was investigated in rats measuring glutathione redox status. For this purpose, the drug was administered to rats as two different single doses (100 and 150 mg/kg, ip) or a repeated dose (500 mg/kg/d, ig, for 5d). Then, total and oxidized glutathione levels were determined in hepatic and cerebral tissues of the rats by an enzymatic cycling assay, and the glutathione redox status was calculated. The possible protective effects of vitamin E or allopurinol against CPFX-induced alterations on glutathione system have also been examined. Following both routes of administration of CPFX, the total glutathione content of the liver, but not of brain decreased significantly. The oxidized glutathione (GSSG) in the brain increased after single or repeated dose treatments, but only with repeated doses of CPFX in the liver. CPFX induced dose-dependent alterations in the glutathione redox status in both tissues. With single doses the effect was more pronounced in cerebral tissue, and with repeated ig doses it was significant in both tissues. Pretreatment of rats with vitamin E or allopurinol before the administration of CPFX provided marked protection against glutathione redox status alterations in both tissues. Our results, thus, indicate that CPFX treatment introduces an oxidative stress in cerebral and hepatic tissues of rat.

Quinolones (Qs) were shown to have cytotoxic effects in various cell lines including human carcinoma cells; however, mechanism of these effects was not fully understood. To investigate the possibility of the involvement of an oxidative stress induction in this mechanism of action, we examined viability of human fibroblast cells exposed to a Q antibiotic, ciprofloxacin (CPFX), and measured lipid peroxidation and total glutathione (GSH) levels, and activities of catalase (Cat), superoxide dismutases (SODs), glutathione peroxidase (GPx). The effects of vitamin E pretreatment on those parameters were also examined. Our results showed that the effect of CPFX on the viability of the cells, as determined by neutral red uptake assay, was time dependent. Cytotoxicity was not observed in the concentration range of 0.0129–0.387 mM CPFX when the cells were incubated for 24 hours. However, significant level of cytotoxicity was observed at concentrations 0.129 and 0.194 mM, and ¶ 0.129 mM, following 48 and 72 hours of exposure, respectively. When the cells were exposed to 0.194 mM CPFX for 48 hours, the level of lipid peroxidation increased and the content of total GSH decreased significantly; activities of total SOD, Mn SOD and CuZn SOD did not change; the decrease observed in the activity of Cat was not significant; and the activity of GPx was highly variable. Vitamin E pretreatment of the cells provided significant protection against CPFX-induced cytotoxicity; lowered the level of lipid peroxidation significantly, but increased the total GSH content only moderately; no change was observed in the activities of Cat and total SOD, but a significant increase in Mn SOD and a significant decrease in Cu Zn SOD were noticed. These results suggested that CPFX-induced cytotoxicity on human fibroblast cell cultures is related to oxidative stress, and vitamin E pretreatment can afford a protection.

Aflatoxin and Ochratoxin known as mycotoxin are the highly toxic metabolic products of molds and one of the significant groups of chemical contaminants that humans are exposed. Exposure to mycotoxins is determined by the analysis of foods or biological fluids. Monitoring the levels of mycotoxin in biological fluids (urine, breast milk, umbilical cord blood, etc.) is accurate and reliable indicator of actual exposure. For this reason measuring contamination levels in breast milk is important. The objective of this study was to determine levels of aflatoxin M1 (AFM1) and ochratoxin A (OTA) in breast milk. Seventy samples of breast milk analyzed in this study were collected from randomly selected volunteer mothers gave birth in a maternity hospital in Ankara and are in lactation period for 20-65 days. The determination of AFM1 and OTA levels were performed by enzyme-linked immunosorbent assay (ELISA). AFM1 and OTA were determined in 9 (12.9%) and 34 (48.6%) samples of human milk, on average 5.73±0.74 ng/L an...

Ciprofloxacin (CPFX) is a widely used fluoroquinolone antibiotic with a broad spectrum of activity. However, clinical experience has shown a possible incidence of undesirable adverse effects including gastrointestinal, skin, hepatic, and central nervous system (CNS) functions, and phototoxicity. Several examples in the literature data indicate that free radical formation might play a role in the mechanism of some of these adverse effects, including phototoxicity and cartilage defects. The purpose of this study is to investigate free radical formation during the metabolism of CPFX in hepatic microsomes using electron spin resonance (ESR) spectroscopy and spin trapping technique. We then investigate the effects of a cytochrome P450 inhibitor, SKF 525A, Trolox, and ZnCl2 on CPFX-induced free radical production. Our results show that CPFX induces free radical production in a dose- and time-dependent manner. The generation of 4-POBN/radical adduct is dependent on the presence of NADPH, CPFX, and active microsomes. Furthermore, free radical production is completely inhibited by SKF 525A, Trolox, or ZnCl2.

Considering that the involvement of reactive oxygen species (ROS) has been implicated in the toxicity of various pesticides, this study was designed to investigate the possibility of oxidative stress induction by cypermethrin, a Type II pyrethroid. Either single (170 mg/kg) or repeated (75 mg/kg per day for 5 days) oral administration of cypermethrin was found to produce significant oxidative stress in cerebral and hepatic tissues of rats, as was evident by the elevation of the level of thiobarbituric acid reactive substances (TBARS) in both tissues, either 4 or 24 h after treatment. Much higher changes were observed in liver, increasing from a level of 60% at 4 h up to nearly 4 times the control at 24 h for single dose. Reduced levels (up to 20%) of total glutathione (total GSH), and elevation of conjugated dienes ( approximately 60% in liver by single dose at 4 h) also indicated the presence of an oxidative insult. Glutathione-S-transferase (GST) activity, however, did not differ from control values for any dose or at any time point in cerebral and hepatic tissues. Pretreatment of rats with allopurinol (100 mg/kg, ip) or Vitamin E (100 mg/kg per day, ig, for 3 days and a dose of 40 mg/kg on the 4th day) provided significant protection against the elevation of TBARS levels in cerebral and hepatic tissues, induced by single high dose of oral cypermethrin administration within 4 h. Thus, the results suggest that cypermethrin exposure of rats results in free radical-mediated tissue damage, as indicated by elevated cerebral and hepatic lipid peroxidation, which was prevented by allopurinol and Vitamin E.

… European Soc Toxicol

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.

Breast feeding is very important in the first year of life. However, breast milk may be contaminated with many residues of xenobiotics and naturally occuring 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 °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. Copyright © 2009 John Wiley & Sons, Ltd.

The aim of this study was to investigate the possible cytotoxic and oxidative stress inducing effects of ciprofloxacin (CPFX) on primary cultures of rat astrocytes. The cultured cells were incubated with various concentrations of CPFX (0.5-300mg/l), and cytotoxicity was determined by neutral red (NR) and MTT assays. Survival profile of cells was biphasic in NR assay: CPFX did not cause any alteration at any concentration for 7h, whereasor =50mg/l concentrations induced significant cell proliferation in incubation periods of 24, 48, 72, and 96h. However, cell proliferation gradually decreased at higher concentrations, and 200 and 300mg/l of CPFX exposure was found to be significantly (p0.05) cytotoxic at all time periods. With MTT assay, no alteration was noted for incubation period of 7h, as observed with NR assay. But, cell viability decreased with approximatelyor =50mg/l CPFX exposure in all other time periods. Cell proliferation was only seen in 24h of incubation with 0.5 and 5mg/l CPFX. Vitamin E pretreatment of cell cultures were found to be providing complete protection against cytotoxicity of 300mg/l CPFX in 96h incubation when measured with both NR and MTT assays. The SOD pretreatment was partially protective with NR assay, but no protection was noted when measured with MTT. A significant enhancement of lipid peroxidation was observed with the cytotoxic concentration of the drug, but total glutathione content and catalase activity of cells did not change. The data obtained in this study suggest that, in accordance with our previous results with fibroblast cells, CPFX-induced cytotoxicity is related to oxidative stress. And the biphasic effect of CPFX possibly resulted from the complex dose-dependent relationships between reactive oxygen species, cell proliferation, and cell viability.

Fluoroquinolones are generally well-tolerated antibiotics in patients. Gastrointestinal, central nervous system, and dermatological adverse events were the most frequent unwanted effects during therapy with these drugs. However, the mechanism of these adverse effects has not yet been elucidated. The aim of this study was to investigate the possible DNA damage-inducing effect of a fluoroquinolone (FQ) antibiotic, ciprofloxacin (CPFX) on primary culture of rat astrocytes. For this purpose, the cultured cells were incubated with various concentrations of CPFX, and DNA damage was monitored by comet assay. Our results showed a concentration-dependent induction of DNA damage by CPFX. Pretreatment of cells with Vitamin E for 4 h provided partial protection against this effect. The data obtained in this study suggest that CPFX-induced DNA damage might be related to oxidative stress and should be considered for further mechanistic studies of central nervous system toxicity of CPFX.

To investigate the possibility of the involvement of an oxidative stress induction in the mechanism of the cytotoxic effect of quinolone antibiotics, we examined the viability of human fibroblast cells exposed to ciprofloxacin (CPFX), and measured the levels of lipid peroxidation (LP), glutathione (GSH), and the activities of the antioxidant enzymes catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPX). The data showed that the effect of CPFX on the viability of cells, as determined by neutral red uptake assay, was time-dependent, and the dose-response relation was biphasic. Cytotoxicity was not observed in the concentration range 5–150 mg/l CPFX when the cells were incubated for 24 h. In contrast, lower concentrations (5 and 12.5 mg/l) of CPFX increased the cell growth in all incubation periods tested. Marked decreases in the viability of fibroblasts were observed at concentrations 50 and 75 mg/l, and ⩾50 mg/l, following 48 and 72 h exposure, respectively ( p < 0.05). However, when the cells were exposed to >75 mg/l CPFX for 48 h, no cytotoxicity was observed. By exposing fibroblast cultures to 75 mg/l CPFX for 48 h, an induction of LP enhancement and a marked decrease in intracellular GSH were observed. Vitamin E pretreatment of the cells lowered the level of LP, increased the total GSH content, and provided significant protection against CPFX-induced cytotoxicity. The biphasic effect of CPFX possibly resulted from the complex dose-dependent relationships between reactive oxygen species (ROS), cell proliferation, and cell viability. It was previously reported, in fact, for several cell models that ROS exert a biphasic effect on cell growth. Furthermore, cultured fibroblasts release their own free radicals, and the inhibition of endogenous ROS inhibits the fibroblast cell proliferation, whereas the effect of exogenous ROS is biphasic.

The oxidant stress-inducing effects of endosulfan, a chlorinated hydrocarbon insecticide of the cyclodiene group, have been examined following ig administration of single and repeated doses. A single dose of 30 mg/kg (approximately 30% LD50) endosulfan significantly (p0.001) increased the TBARS and, hence, the lipid peroxidation in cerebral and hepatic tissues of rats. Administration of endosulfan with doses of 10 or 15 mg/kg/d for 5 d has also induced lipid peroxidation significantly (p0.05). The same doses caused a significant alteration in glutathione redox status of cerebral and hepatic tissues, where total glutathione and oxidized glutathione were measured by an enzymatic cycling procedure. Selenium levels were also determined and compared with controls. With repeated doses, oxidant stress was more pronounced in cerebral tissue, where endosulfan shows a GABA-antagonistic activity. The possible relationship between the neurotoxicity of endosulfan and its oxidant stress-inducing effect was discussed.