Comparative evaluation of the effects of bisphenol derivatives on oxidative stress parameters in HepG2 cells.

Bisphenol A (BPA) BPA is an endocrine-disrupting chemical that has a wide range of uses. Exposure to BPA can be by oral, inhalation, and parenteral routes. Although its use in several products is limited, there is still concern on its adverse health effects, particularly for susceptible populations like children. Alternative bisphenols, such as bisphenol S (BPS) and bisphenol F (BPF), are now being used instead of BPA, although there is little information on the toxicity of these bisphenols. BPF is used as a plasticizer in the production of several industrial materials as well as in the coating of drinks and food cans. BPS is used in curing fast-drying epoxy glues, as a corrosion inhibitor and as a reactant in polymer reactions. In this study, the possible toxic effects of BPA, BPS, and BPF in HepG2 cells were evaluated comparatively. For this purpose, their effects on cytotoxicity, production of intracellular reactive oxygen species (ROS), oxidant/antioxidant parameters, and DNA damage have been examined. The cytotoxicity potentials of different bisphenols were found to be as BPS > BPF > BPA. All bisphenol derivatives caused increases in intracellular ROS production. We observed that all bisphenol derivatives cause an imbalance in some oxidant/antioxidant parameters. Bisphenols also caused significant DNA damage in order of BPF > BPA > BPS. We can suggest that both of the bisphenol derivatives used as alternatives to BPA also showed similar toxicities and may not be considered as safe alternatives. Mechanistic studies are needed to elucidate this issue.

Toxic effects of Aroclor 1254 on rat liver and modifying roles of selenium.

Polychlorinated biphenyls (PCBs) were used in different industrial areas and banned due to their high toxicity. Aroclor 1254 (A1254), commercial PCB congener, accumulates in environment leading to high human exposure. A1254 may cause hepatotoxicity, metabolic and endocrine disorders. In our study, 3-week-old male rats were separated into 6 groups: C (0.15 mg/kg Se in diet); SeS (1 mg/kg Se in diet); SeD (0.05 mg/kg Se in diet); A1254 receiving groups (A; ASeS; ASeD) were given 10 mg/kg/day A1254 orally for last 15 days of feeding period with control, SeD or SeS diet, respectively, for 5 weeks. Histopathology, oxidant/antioxidant balance, apoptosis and cell cycle proteins (p53, p21) in liver were evaluated. Our results suggest that A1254 leads to changes in histology, oxidative stress and apoptosis. Selenium deficiency augments oxidative stress and apoptosis while selenium supplementation is partially protective. More mechanistic in vivo experiments are necessary for evaluation of hepatotoxicity of PCBs.

Effects of prenatal and lactational bisphenol a and/or di(2-ethylhexyl) phthalate exposure on male reproductive system.

Bisphenol A (BPA) and phthalates are abundantly used endocrine disrupting chemicals (EDCs). The aim of this study was to evaluate the effects of single and combined exposures to BPA and/or di(2-ethylhexyl) phthalate (DEHP) in prenatal and lactational period on rat male reproductive system in later stages of life. Pregnant Sprague-Dawley rats were divided randomly to four groups (n = 3/group): Control (corn oil); DEHP (30 mg/kg/day); BPA (50 mg/kg/day); and BPA+ DEHP (30 mg/kg/day DEHP and 50 mg/kg/day BPA). Groups exposed to EDCs through 6-21 gestational days and lactation period by intragastric lavage. Male offspring (n = 6/group) from each mother were fed till adulthood and were then euthanized. Later, reproductive hormones, sperm parameters, and oxidative stress parameters were determined. In conclusion, we can suggest that prenatal and lactational exposure to BPA and DEHP may cause adverse effects in male reproductive system in later stages of life especially after combined exposure.

The effects of prenatal and lactational bisphenol A and/or di(2-ethylhexyl) phthalate exposure on female reproductive system.

Bisphenol A (BPA) and di(2-ethylhexyl) phthalate (DEHP) are endocrine disrupting chemicals (EDCs) that are abundantly used in polyvinyl chloride plastics, polycarbonates and epoxy resins. Prenatal and early postnatal exposures to EDCs are suggested to be more critical. Such exposures can lead to reprotoxic effects, hormonal and metabolic consequences in adulthood. Moreover, combined exposure to different EDCs can lead to more serious adverse effects, some of which cannot be predicted by examining their individual toxicity profiles. This study aimed to evaluate effects of single and combined prenatal and lactational exposures to BPA and/or DEHP on female reproductive hormones and ovarian follicle development. Pregnant Sprague-Dawley rats were divided randomly to four groups (n = 3/group): Control (received vehicle only); DEHP (30 mg/kg/day); BPA (50 mg/kg/day) and BPA + DEHP (30 mg/kg/day DEHP; 50 mg/kg/day BPA) through 6-21 gestational days and lactation by intra-gastric lavage. Female offspring (n = 6/group) were fed until the end of twelfth postnatal week and then euthanized. Reproductive hormones, ovarian follicle numbers and ovarian development were determined. Plasma testosterone and estradiol levels of BPA and BPA + DEHP groups were significantly lower than control. In BPA group, the number of tertiary ovarian follicles decreased significantly compared to control. In the combined exposure group, the number of corpus luteum (29%), as well as the number of primordial follicles (36%), showed marked decreases compared to control group. It can be suggested that early life exposure to BPA and DEHP may cause late life adverse effects in female reproductive system, especially after combined exposure.

The effects of different bisphenol derivatives on oxidative stress, DNA damage and DNA repair in RWPE-1 cells: A comparative study.

Bisphenol A (BPA) is a well-known endocrine disruptor and it is widely used mainly in the plastics industry. Due to recent reports on its possible impact on health (particularly on the male reproductive system), bisphenol F (BPF) and bisphenol S (BPS) are now being used as alternatives. In this study, RWPE-1 cells were used as a model to compare cytotoxicity, oxidative stress-causing potential and genotoxicity of these chemicals. In addition, the effects of the bisphenol derivatives were assessed on DNA repair proteins. RWPE-1 cells were incubated with BPA, BPF, and BPS at concentrations of 0-600 µM for 24 h. The inhibitory concentration 20 (IC20 , concentration that causes 20% of cell viability loss) values for BPA, BPF, and BPS were 45, 65, and 108 µM, respectively. These results indicated that cytotoxicity potentials were ranked as BPA > BPF > BPS. We also found alterations in superoxide dismutase, glutathione peroxidase and glutathione reductase activities, and glutathione and total antioxidant capacity in all bisphenol-exposed groups. In the standard and modified Comet assay, BPS produced significantly higher levels of DNA damage vs the control. DNA repair proteins (OGG1, Ape-1, and MyH) involved in the base excision repair pathway, as well as p53 protein levels were down-regulated in all of the bisphenol-exposed groups. We found that the BPA alternatives were also cytotoxic and genotoxic, and changed the expressions of DNA repair enzymes. Therefore, further studies are needed to assess whether they can be used safely as alternatives to BPA or not.

The Effects of Polymer Coating of Gold Nanoparticles on Oxidative Stress and DNA Damage.

Gold nanoparticles (AuNPs) have been widely used in many biological and biomedical applications. In this regard, their surface modification is of paramount importance in order to increase their cellular uptake, delivery capability, and optimize their distribution inside the body. The aim of this study was to examine the effects of AuNPs on cytotoxicity, oxidant/antioxidant parameters, and DNA damage in HepG2 cells and investigate the potential toxic effects of different surface modifications such as polyethylene glycol (PEG) and polyethyleneimine (PEI; molecular weights of 2,000 (low molecular weight [LMW]) and 25,000 (high molecular weight [HMW]). The study groups were determined as AuNPs, PEG-coated AuNPs (AuNPs/PEG), low-molecular weight polyethyleneimine-coated gold nanoparticles (AuNPs/PEI LMW), and high-molecular weight polyethyleneimine-coated gold nanoparticles (AuNPs/PEI HMW). After incubating HepG2 cells with different concentrations of nanoparticles for 24 hours, half maximal inhibitory concentrations (the concentration that kills 50% of the cells) were determined as 166.77, 257.73, and 198.44 µg/mL for AuNPs, AuNPs/PEG, and AuNPs/PEI LMW groups, respectively. Later, inhibitory concentration 30 (IC30, the concentration that kills 30% of the cells) doses were calculated, and further experiments were performed on cells that were exposed to IC30 doses. Although intracellular reactive oxygen species levels significantly increased in all nanoparticles, AuNPs as well as AuNPs/PEG did not cause any changes in oxidant/antioxidant parameters. However, AuNPs/PEI HMW particularly induced oxidative stress as evidence of alterations in lipid peroxidation and protein oxidation. These results suggest that at IC30 doses, AuNPs do not affect oxidative stress and DNA damage significantly. Polyethylene glycol coating does not have an impact on toxicity, however PEI coating (particularly HMW) can induce oxidative stress.

Bisphenol A and phthalate levels in adolescents with polycystic ovary syndrome.

Endocrine disruptors have been proposed in the etiology of polycystic ovary syndrome (PCOS) as they have the potency to interfere with hormone-sensitivity systems. The aim of this study was to evaluate the levels of bisphenol A (BPA) and phtalates in adolescents with PCOS. Sixty-two girls with PCOS and 33 controls, age 12-18 years were enrolled in the study. The diagnosis of PCOS was made using modified Rotterdam criteria. Urinary BPA levels were measured using high-performance liquid chromatography. Di-(2-ethylhexyl)-phthalate (DEHP), the most commonly used phthalate and mono-(2-ethylhexyl)-phthalate (MEHP), its main metabolite were measured by using high-performance liquid chromatography. Adolescents with PCOS had markedly increased BPA levels (15.89 µg/g creatine ± 1.16) when compared with the control group (7.30 µg/g creatine ± 1.38) (p = .016). In adolescents with PCOS, BPA was significantly correlated with polycystic morphology on ultrasound but not with obesity androgen levels, or other metabolic parameters. Patients with PCOS (DEHP: 0.40 ppm ± 0.24, MEHP: 0.13 ppm ± 0.23) and controls (DEHP: 0.49 ppm ± 0.27, MEHP: 0.14 ppm ± 0.3) had similar serum phtalate concentrations (p = .7 and p = .3, respectively). Exposure to specific endocrine disruptors such as BPA could modify neuroendocrine, reproductive, and metabolic regulation favoring PCOS development in adolescents.

The effects of amniotic fluid and foetal cord blood cotinine concentrations on pregnancy complications and the anthropometric measurements of newborns.

Our objective was determining the effects of amniotic fluid (AF) and fetal cord blood (FCB) cotinine concentrations on pregnancy complications and the anthropometric measurements in the newborns whose mothers underwent amniocentesis. This study was conducted as a case-control study, in Turkey. A total of 250 pregnant women with amniocentesis indication were recruited into the study and the cotinine levels in the AF and FCB were determined. A smoking habit did not statistically affect the incidence of pregnancy complications (p>.05). The birth weights of the newborns were negatively correlated with the AF cotinine levels. The incidences of low birth weight, low Apgar scores and RDS were positively correlated with higher levels of cotinine in AF and FCB. It is important for healthcare staff to provide training and consultancy services for the health improvement of pregnant women and the prevention of smoking during pregnancy. Impact statement What is already known on this subject? The pre-pregnancy smoking habit usually continues during the pregnancy. A significant negative correlation was present between the foetal cord blood cotinine levels and the birth weight. What do the results of this study add? The anthropometric measurements of the newborns born from mothers with high AF cotinine levels were lower than newborns born from mothers with low amniotic fluid cotinine levels. Respiratory Distress syndrome is more often determined in newborns born from mothers with high AF cotinine levels. What are the implications of these findings for clinical practice and/or further research? Future studies should be performed to investigate the effects of cigarette smoking on the health problems, the growth characteristics and the neurological development of newborns and infants within the first year of life.

Oxidative stress markers, trace elements, and endocrine disrupting chemicals in children with Hashimoto's thyroiditis.

In this study, we aimed to investigate whether bisphenol A (BPA) and di-(2-ethylhexyl) phthalate (DEHP) exposure have any association with Hashimoto's thyroiditis (HT) and its biomarkers and to determine whether oxidative stress biomarkers and trace element levels showed any alterations in children with HT. We found that superoxide dismutase and glutathione peroxidase activities are lower in HT group from control (24% and 46%, respectively, p < 0.05). Zinc levels were significantly lower in HT group vs. control. In addition, the levels of mono-(2-ethylhexyl) phthalate (MEHP) which is the primary metabolite for DEHP, were markedly higher in HT group compared to control (p < 0.05). A negative correlation was observed between urinary BPA levels and fT4. In children with HT, oxidant/antioxidant balance is changed and these differences may be related by EDC exposure, the importance of which should be elucidated with further studies.

Evaluation of skin irritation potentials of different cosmetic products in Turkish market by reconstructed human epidermis model.

Human skin is a protective barrier against the toxic effects of cosmetics. Marketing of cosmetic products with ingredients tested on animals was prohibited in 2013. Since then, safety evaluation of cosmetic products is performed by using alternative in vitro toxicity tests. In vitro 3-D reconstructed human epidermis (RhE) tissue models are now used to define skin irritation/corrosion potentials of cosmetic ingredients and end-products. The main aim of this study was to evaluate skin irritation potentials of topically used cosmetic end-products which were marketed in Turkey during 2015-2017, by using the EpiDerm in vitro 3D-human skin model. Sixty widely used cosmetic products were collected from different markets/cosmetic shops. Among hair care products, only one shampoo was found to be strong/severe skin irritant/possible corrosive while 22 shampoos were moderate skin irritant and 11 shampoos were moderate to mild skin irritant. Among 6 skin care products, one was found to be moderate to mild skin irritant. We can suggest that alternative in vitro tests should continuously be used to test both the ingredients and the final cosmetic formulations.

Impact of selenium status on Aroclor 1254-induced DNA damage in sperm and different tissues of rats.

Aroclor 1254 is a commercial mixture of polychlorinated biphenyls (PCBs), which are widespread environmental pollutants. It is used as non-flammable heat transfer agent and plasticizer. Animal studies have reported that Aroclor 1254 exerted toxic effects in different organs and systems. Although the evidences are limited, it seems reasonable that Aroclor 1254 may have a potential for similar adverse effects in humans. Selenium (Se) is a trace element and an important component of cellular antioxidant defense. This study was designed to investigate the effects of different Se status on the genotoxicity of Aroclor 1254 in sperm and different organs of Sprague-Dawley rats using Comet assay. Se deficiency (SeD) was generated by feeding 3-week old Sprague-Dawley rats with <0.05 Se mg/kg diet for 5 weeks. Se supplementation groups (SeS) were fed with 1 mg Se/kg diet. Aroclor 1254-treated rats received 10 mg/kg dose by gavage during the last 15 d of feeding period. SeD increased DNA damage in all of the organs as well as in lymphocytes and sperm. Aroclor 1254 treatment caused pronounced changes in liver, kidney and brain cells along with marked increases in lymphocytes and sperm. Se supplementation provided full or partial protection decreases in Aroclor 1254-induced DNA damage in sperm and all of tissues. Se deficiency aggravated the toxicity by increasing DNA damage caused by Aroclor 1254. Further studies should be performed to clarify the mechanism(s) underlying the protective role of Se status against Aroclor 1254 genotoxicity.

Impaired antioxidant enzyme functions with increased lipid peroxidation in epithelial ovarian cancer.

We aimed to identify the possible role of oxidant-antioxidant status in epithelial ovarian cancer (EOC) by measuring (a) antioxidant enzyme (AOE) activities [total superoxide dismutase (SODtotal ), manganese-SOD (Mn-SOD), copper,zinc-SOD (Cu,Zn-SOD), catalase (CAT) and glutathione peroxidase (GPx1)], (b) Mn-SOD protein expression, (c) lipid peroxidation markers [malondialdehyde (MDA), 8-epi-prostaglandin-F2α (8-epi-PGF2α)] and by evaluating the possible correlations between tumor biomarkers, reproductive hormone levels and all measured parameters, comprehensively. The data obtained from the patients with EOC (M, n = 26) evaluated according to the histopathological/clinical characteristics of tumors and compared with data of healthy controls [Ctissue (C1) and Cblood/urine (C2), n = 30, respectively). Significantly, low activities of tumor SODtotal (52%), Mn-SOD (42%), Cu,Zn-SOD (55%); high activities of tumor and erythrocyte CAT (66%, 33% respectively) and tumor GPx1 (60%); high levels of tumor Mn-SOD protein expression; tumor MDA (193%) and urinary 8-epi-PGF2α (179%) were observed in serous EOC tumors (M1, n = 18) compared with controls (P < 0.05). However, higher levels of tumor MDA, Mn-SOD protein expression and urinary 8-epi-PGF2α were observed along with lower tumor CAT activity in poorly differentiated or undifferentiated (grade 3, G 3) versus well or moderately well differentiated (grade 1-2, G 1-2) serous EOC tumors. Obtained data indicate the presence of a severe redox imbalance in EOC and draw attention to the criticial role of AOEs in the pathogenesis of the disease. © 2017 IUBMB Life, 69(10):802-813, 2017.

The ameliorating effects of vitamin E on hepatic antioxidant system and xenobiotic-metabolizing enzymes in fenvalerate-exposed iodine-deficient rats.

This study investigated the effects of vitamin E (VE) on hepatic antioxidant system and drug-metabolizing enzymes in fenvalerate (FEN)-exposed iodine-deficient (ID) Wistar rats. ID was produced by perchlorate containing drinking water. VE was introduced by a loading dose of 100 mg/kg/d, i.g. for the first three days in the last week of feeding period; then with a single maintenance dose of 40 mg/kg on the 4th day. During last week, FEN groups (F) received 100 mg/kg/d, i.p. FEN. VE alone did not significantly affect thyroid hormones and antioxidant parameters; however, significantly increased total cytochrome P450 (38%) and cytochrome b5 levels (36%). In all ID groups, plasma thyroid-stimulating hormone (TSH) levels increased markedly, but remained at control level in vitamin E plus FEN receiving iodine-deficient group (IDVF) group. Glutathione peroxidase activity showed marked increases in F (19%) and FEN-exposed iodine-deficient group (IDF, 48%) groups. FEN treatment significantly increased total cytochrome P450 (28%) and thiobarbituric acid reactive substance levels (36%), as well as 7-ethoxyresorufin O-deethylase (120%), 7-penthoxyresorufin O-deethylase (139%) and glutathione S-transferase (15%) activities and decreased total glutathione concentrations (28%) versus control. Overall results suggest that vitamin E has ameliorating effects on the measured parameters in ID and/or FEN exposure.

The evaluation of possible role of endocrine disruptors in central and peripheral precocious puberty.

Exposure to environmental chemicals can affect genetic and epigenetic molecular pathways and may cause altered growth and development. Among those exposures, endocrine-disrupting chemicals (EDCs) are of particular concern as humans are abundantly exposed to these chemicals by various means in every period of life. Several well-known environmental chemicals, including phthalates and bisphenol A (BPA), are classified as EDCs. These EDCs are suggested to play roles in early onset of puberty in girls. The aim of this study is to determine plasma phthalate (di(2-ethylhexyl)phthalate [DEHP] and its main metabolite mono(2-ethylhexyl)phthalate [MEHP]) and urinary BPA levels in girls with idiopathic central precocious puberty (CPP) and peripheral precocious puberty (PPP). This study was performed on newly diagnosed idiopathic central precocious puberty (CPP) patients (n = 42) and peripheral precocious puberty (PPP) (n = 42) patients, who were admitted to Keçiören Training and Research Hospital, Clinic of Pediatric Endocrinology between August 2012 and -July 2013. Nonobese healthy girls (n = 50) were used as the control group. Urinary BPA levels were not statistically different in control, PPP and CPP groups (medians 10.91, 10.63 and 10.15 µg/g creatinine, respectively; p > 0.05). Plasma DEHP levels were significantly higher in PPP group when compared to control. Plasma MEHP levels were not significantly different in control and PPP groups (p > 0.05). However, in CPP group, both plasma DEHP and MEHP levels were significantly higher than control and PPP groups. This study showed that phthalates might play a role in the occurence of CPP in girls.

The effects of season and gender on the serum aflatoxins and ochratoxin A levels of healthy adult subjects from the Central Anatolia Region, Turkey.

PURPOSE: This study was undertaken to determine the effects of season and gender on serum aflatoxin (AF) levels (AFG1, AFB1, AFG2 and AFB2) and ochratoxin A (OTA) concentrations of healthy adult population living in Central Anatolia Region of Turkey. METHODS: AF levels were measured by high-performance liquid chromatography (HPLC) and OTA levels were measured by enzyme-linked immunosorbent assay (ELISA) in serum samples of healthy adults (n = 233). RESULTS: In summer and winter, total AF levels in females were 0.98 ± 0.10 and 0.94 ± 0.12 ng/ml and in males 1.35 ± 0.17 and 0.93 ± 0.11 ng/ml, respectively. Male subjects had significantly higher serum total AF levels in summer compared with females (~38%). There was no marked seasonal change in AFG1, AFB1 and AFG2 concentrations in the whole population, except AFB2. Both of the genders had significantly higher OTA levels in winter compared with summer (~60%). CONCLUSIONS: Overall results suggest that Central Anatolia residents are continuously exposed to AFs and OTA. Besides, season and gender can be effective in mycotoxin exposure.

Oxidant and antioxidant status in neonatal proven and clinical sepsis according to selenium status.

BACKGROUND: Selenium is a trace element required for the functioning of the immune system. Neonatal sepsis is a serious condition leading to morbidity and mortality in neonates worldwide. The purpose of this study was to measure selenium and plasma selenoprotein P (SePP), selenoenzyme activity, and alterations in oxidant/antioxidant status with immune biomarkers in neonates with clinical (n = 27) and proven neonatal sepsis (n = 25). METHODS: Erythrocyte selenium and SePP; plasma lipid peroxidation (LP), protein oxidation and total antioxidant capacity and erythrocyte total glutathione (GSH) concentration; erythrocyte glutathione peroxidase (GPx), thioredoxin reductase (TrxR), catalase (CAT) and total superoxide dismutase (SOD) activity were measured spectrophotometrically/spectrofluorometrically. Plasma interleukin 2 and 6 were also measured. RESULTS: Erythrocyte selenium and SePP were markedly lower both in the clinical and proven sepsis groups versus control. Erythrocyte GPx activity was higher only in the clinical sepsis group. TrxR activity was markedly lower in proven sepsis. SOD activity and GSH were markedly higher both in clinical sepsis and in proven sepsis. CAT activity was significantly higher both in clinical sepsis and in proven sepsis. LP and protein oxidation were significantly higher in both of the sepsis groups. CONCLUSIONS: Both selenium-dependent and selenium-independent blood redox systems were altered in sepsis, suggesting that sepsis causes an imbalance between cellular antioxidant and oxidant states.

Genotoxicity of phthalates.

Many of the environmental, occupational and industrial chemicals are able to generate reactive oxygen species (ROS) and cause oxidative stress. ROS may lead to genotoxicity, which is suggested to contribute to the pathophysiology of many human diseases, including inflammatory diseases and cancer. Phthalates are ubiquitous environmental chemicals and are well-known peroxisome proliferators (PPs) and endocrine disruptors. Several in vivo and in vitro studies have been conducted concerning the carcinogenic and mutagenic effects of phthalates. Di(2-ethylhexyl)-phthalate (DEHP) and several other phthalates are shown to be hepatocarcinogenic in rodents. The underlying factor in the hepatocarcinogenesis is suggested to be their ability to generate ROS and cause genotoxicity. Several methods, including chromosomal aberration test, Ames test, micronucleus assay and hypoxanthine guanine phosphoribosyl transferase (HPRT) mutation test and Comet assay, have been used to determine genotoxic properties of phthalates. Comet assay has been an important tool in the measurement of the genotoxic potential of many chemicals, including phthalates. In this review, we will mainly focus on the studies, which were conducted on the DNA damage caused by different phthalate esters and protection studies against the genotoxicity of these chemicals.

Effects of single or combined exposure to bisphenol A and mono(2-ethylhexyl)phthalate on oxidant/antioxidant status, endoplasmic reticulum stress, and apoptosis in HepG2 cell line.

Endocrine disrupting chemicals (EDCs) may affect many biological processes like growth and stress response. Bisphenol A (BPA) is a plasticizer that is used to harden plastics and polycarbonates. Phthalates are used to add flexibility to polyvinyl chloride containing plastics. The main metabolite of di(2-ethylhexyl) phthalate (DEHP) is mono(2-ethylhexyl) phthalate (MEHP) and it is even more toxic than the parent compound. Humans are usually exposed to these chemicals in mixtures by different routes starting from fetal period. However, there are not many studies in literature that investigate the combined effects of these chemicals. The aim of this study is to investigate toxic effects of BPA and/or MEHP on HepG2 cell line. We have evaluated cytotoxicity, cytomorphological, apoptotic changes, oxidative stress, oxidant/antioxidant status alterations, and endoplasmic reticulum (ER) stress. Combined exposure to BPA and MEHP caused alterations in oxidant/antioxidant status and ER stress marker proteins in both cytoplasmic and nuclear cellular fractions. We can suggest that combined exposure to EDCs may cause serious toxicological outcomes and more mechanistic studies are needed to determine the combined toxic effects.

Neuroendocrine disruption by bisphenol A and/or di(2-ethylhexyl) phthalate after prenatal, early postnatal and lactational exposure.

Bisphenol A (BPA) and di(2-ethylhexyl)phthalate (DEHP) are abundant endocrine disrupting chemicals (EDCs). In recent years, studies showed that EDCs may lead to neurodevelopmental diseases. The effects of prenatal exposure to these chemicals may have serious consequences. Moreover, exposure to EDCs as a mixture may have different effects than individual exposures. The present study aimed to determine the toxicity of BPA and/or DEHP on central nervous system (CNS) and neuroendocrine system in prenatal and lactational period in Sprague-Dawley rats. Pregnant rats were randomly divided into four groups: control (received vehicle); BPA group (received BPA at 50 mg/kg/day); DEHP group (received DEHP at 30 mg/kg/day); and combined exposure group (received both BPA at 50 mg/kg/day and DEHP at 30 mg/kg/day) during pregnancy and lactation by oral gavage. At the end of lactation, male offspring (n = 6) were randomly grouped. The alterations in the brain histopathology, neurotransmitter levels and enzyme activities in the cerebrum region, oxidative stress markers, and apoptotic effects in the hippocampus region were determined at adulthood. The results showed that exposure to EDCs at early stages of life caused significant changes in lipid peroxidation, total GSH and neurotransmitter levels, and activities of neurotransmitter-related enzymes. Moreover, BPA and/or DEHP led to apoptosis and histopathologic alterations in the hippocampus. Therefore, we can suggest that changes in oxidant/antioxidant status, as well as in neurotransmitters and related enzymes, can be considered as the underlying neurotoxicity mechanisms of BPA and DEHP. However, more mechanistic studies are needed.

The association between urinary BPA levels and medical equipment among pediatric intensive care patients.

We aim to evaluate urinary total BPA (tBPA) levels and association with medical devices used on patients in pediatric intensive care units. This cross-sectional descriptive study included 117 critically ill children. Urinary tBPA levels were determined using high-performance liquid chromatography. General estimating equations with repeated measures analyzed the effect of interventions and devices on urinary BPA levels. A total of 292 urine samples taken from 117 child intensive care patients were studied. When age, sex, and body mass index-for age z-scores were controlled, cases having endotracheal intubation showed higher urinary tBPA levels (p = 0.003) and hemodialyzed patients had considerably higher urinary tBPA levels (p = 0.004). When confounding factors were controlled, cases using both multiple iv treatment and more than four medical devices showed higher urinary tBPA levels than their counterparts (p = 0.007 and p = 0.028, respectively). The use of certain medical devices and interventions could increase BPA exposure in pediatric intensive care patients.