Aylin Gürbay

Cypermethrin-induced oxidative stress in rat brain and liver is prevented by Vitamin E or allopurinol

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.

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 todays 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.

Induction of lipid peroxidation and alteration of glutathione redox status by endosulfan

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 (∼30% LD50) endosulfan significantly (p<0.001) 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 (p<0.05). 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.

Microsomal metabolism of ciprofloxacin generates free radicals.

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.

Ciprofloxacin‐Induced Glutathione Redox Status Alterations in Rat Tissues

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.

Aflatoxin M1 levels in commonly consumed cheese and yogurt samples in Ankara, Turkey

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 consumed cheese and yogurt samples for aflatoxin M1 contamination in Turkey.

Biphasic Response of Ciprofloxacin in Human Fibroblast Cell Cultures

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.