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Numerous investigations have demonstrated that phototherapy (PT) directly or indirectly causes ductal patency by photorelaxation effect. In this observational study, we aimed to assess the effect of PT on the incidence of patent ductus arteriosus (PDA) together with prostaglandins (PGE2) and (PGI2) levels in preterm infants.Preterm infants whose gestational age34 weeks and who required PT in the first 3 d of life were enrolled in this prospective study. The clinical signs of PDA, the data of detailed echocardiographic study were recorded and plasma PGE2 and PGI2 levels were measured before and after PT. The outcome measures were the status of ductus arteriosus and alterations of PGE2 and PGI2 levels under the effect of PT.A total of 44 preterm infants were enrolled in the study, of these 21 (47.7%) were in Group 1 (Non-PDA Group) and 23 (52.3%) were in Group 2 (PDA Group). After PT, ductal reopening occurred in three infants (14.3%) in Group 1, while ductus closed in four infants in Group 2 (17.3%). PT does not seem to effect ductal patency for both groups (p=0.250 and p=0.125, respectively). PGE2 levels were not different before and after PT for both groups (p=0.087, p=0.408, respectively). However, PGI2 levels were significantly decreased after PT in both groups (p=0.006, and p=0.003, respectively).There was no effect of PT on ductal patency. We can conclude that PGs were eliminated simultaneously with ductal closure and photorelaxation effect did not influence PG levels.

ObjectiveTo determine the serum concentrations of aflatoxin B1(AFB1), aflatoxin B2(AFB2), aflatoxin G1(AFG1) and aflatoxin G2(AFG2) in the healthy adult population living in both the Black Sea and Mediterranean regions of Turkey and to investigate the regional, seasonal and gender variability in aflatoxins (AF) exposure in these regions.DesignSerum AFB1, AFB2, AFG1and AFG2concentrations were analysed by HPLC.SettingsIn total, four hundred and eighty-four serum samples were analysed.SubjectsFour hundred and eighty-four healthy adult volunteers living in rural areas of the Black Sea and Mediterranean regions of Turkey were studied.ResultsThe mean serum concentration of total AF in the Black Sea region was 1·33 ppb (min–max 0·15–3·38 ppb) and 0·90 ppb (min–max 0·18–2·48 ppb) for summer and winter, respectively. In the Mediterranean region, the mean serum concentration of total AF was determined as 0·55 ppb (range 0·04–1·72 ppb) for summer and 0·45 ppb (range 0·12–1·43 ppb) for winter. The total AF concentrations in serum samples were statistically higher in summer compared with winter for the two regions. The differences between the regions were statistically significant concerning all samples, with higher total AF concentrations in the Black Sea region.ConclusionsThe overall results suggest that the Turkish population living in these two regions is continuously exposed to AF, particularly in the summer, and that mycotoxin contamination in food should be monitored routinely for food safety and human health.

This study was designed to investigate the possible protective effect of lycopene against the renal toxic effects of OTA. Male Sprague-Dawley rats (

Insecticides have a great importance in the increase of agricultural productivity and maintaining of public health. However, they can cause serious poisoning cases and even deaths at times due to accidental, intentional or occupational exposures. Thus insecticide poisoning cases are encountered frequently in Turkey as well as throughout the world. The first part of this review focused on the toxicological profiles of various insecticide groups (organophosphates, organochlorine insecticides, pyrethrines, pyrethroids, amitraz and other insectides (avermectines, diethyl-m-toluamid (DEET) and neonicotinik acid derivatives), and diagnosis and treatment of poisoning with those insecticides marketed in Turkey. In the second part, the studies on insecticide poisonings which were conducted in Drug and Poison Centers, Institutes of Forensic Science, Departments of Forensic Medicine, University and State Hospitals and Medical Centers in Turkey were evaluated with the aim of contributing the whole picture of the situation in Turkey. In review of these reports it was found that the most frequently occurred cases resulted from exposures with organophosphate compounds, and females were more vulnerable than males. It is noteworthy that there are numerous reports in Turkey regarding poisoning cases with amitraz, which was used mostly as a veterinary drug, especially in children despite no cases in the developed OZET Insektisitler, hem tarimsal uretimin artirilmasinda hem de ev ve toplum sagliginda cok onemli bir yere sahiptir. Ancak uretim, ambalajlama ya da kullanimlari sirasinda gerekli ozenin gosterilmemesi ya da intihar gibi suistimale bagli olarak, kazai, kasti veya mesleki temas nedeniyle ciddi zehirlenmelere hatta bazen olumlere yol acabilmektedirler. Tum dunyada oldugu gibi ulkemizde de insektisitlerle zehirlenme olgularina siklikla rastlanmaktadir. Bu calismanin ilk bolumunde ulkemizde pazarlanmakta olan insektisit gruplari olan organofosfatlar, organoklorlular, piretrinler ve piretroidler, amitraz ve diger insektisitlerin (avermektinler, dietil-m-toluamid (DEET) ve neonikotinik asit turevleri) genel ozellikleri, toksik etkileri, zehirlenme tani ve tedavi yaklasimlari konusundaki bilgiler sunulmustur. Ikinci bolumde ise Turkiye’de pestisit / insektisit zehirlenmelerinin epidemiyolojisi ve tedavi yaklasimlari konusunda ilac ve zehir bilgi merkezleri, adli tip enstituleri, universitelerin adli tip ana bilim dallari, universite hastaneleri, devlet hastaneleri veya saglik merkezleri tarafindan bildirilmis olan calisma ornekleri degerlendirilerek Turkiye genelini kapsayan tablonun olusturulmasina katkida bulunulmasi hedeflenmistir. Bu raporlarin degerlendirilmesinde en siklikla olgularin organofosfatli bilesiklere maruziyet sonucunda gelistigi, ozellikle intiharlarda olmak uzere kadinlarin daha duyarli oldugu belirlenmistir. Gelismis ulkelerde rastlanilmamakla Turk Hijyen ve Deneysel Biyoloji Dergisi 1 Hacettepe Universitesi, Eczacilik Fakultesi, Ilac ve Zehir Bilgi Birimi, ANKARA 2 Hacettepe Universitesi, Eczacilik Fakultesi, Farmasotik Toksikoloji Anabilim Dali, ANKARA Gelis Tarihi / Received : Kabul Tarihi / Accepted : Iletisim / Corresponding Author : Belma KOCER-GIRAY Hacettepe Universitesi, Eczacilik Fakultesi, Farmasotik Toksikoloji Anabilim Dali, ANKARA Tel : +90 312 305 21 78 E-posta / E-mail : belmagiray@yahoo.fr 14.03.2012 24.05.2013 DOI ID : 10.5505/TurkHijyen.2013.05935 Ozkaya G, Celiker A, Kocer-Giray B. Insektisit zehirlenmeleri ve Turkiye’deki durumun degerlendirilmesi. Turk Hij Den Biyol Derg, 2013; 70(2): 75-102. Cilt 70  Sayi 2  2013 Turk Hij Den Biyol Derg 76 Pestisitler, zararli organizmalari engellemek, zararlarini azaltmak veya kontrol altina almak amaciyla kullanilan bilesiklerdir. Bu grup bilesikler icinde yer alan ve boceklere karsi kullanilan insektisitler, kuresel anlamda daha cok, tarimsal uretimi artirmak amaciyla kullanilan urunler olarak bilindikleri icin bircok yerde “tarim ilaci” olarak da adlandirilmaktadirlar. Diger taraftan, evde ve diger pek cok alanda kullanimlari soz konusudur. Yaygin kullanim alanlari ile paralel olarak, kullanim sirasinda koruyucu giysi ve maske kullanmamak gibi dikkatsizlikler, ambalajlama ve saklama yanlisliklari ve bilincsiz tuketim gibi nedenler ve intihar amacli alima bagli olarak toplumda insektisit zehirlenmeleri ile karsilasilmaktadir. Bu derlemede, insektisitler siniflandirilarak genel ozellikleri, toksik etkileri, zehirlenme tani ve tedavi yaklasimlari ile birlikte Turkiye’de karsilasilan insektisit zehirlenmeleri konusunda bilgi aktarilacaktir. 1. Insektisitlerin Siniflandirilmasi, Toksik Etkileri, Zehirlenme Tani ve Tedavileri Insektisitler kimyasal yapilarina ve etki mekanizmalarina gore farkli gruplar altinda siniflandirilirlar. 1.1. Asetilkolinesteraz Inhibitorleri Organofosfatli insektisitler ve karbamatlar bu grupta yer almaktadir. Organofosfatli insektisitler, ilk kez 1937 yilinda Alman kimyaci Schrader ve ekibi tarafindan sentezlenmis ve ardindan bu bilesiklerin bazilari (sarin, tabun, soman) potansiyel sinir gazi olarak 2. Dunya Savasi sirasinda gelistirilmistir. Karbamat esterleri de ilk olarak 1930’larda sentezlenmis ve fungusit olarak kullanilmistir. Insektisit aktivitesi ve dusuk memeli toksisitesine sahip olmalari nedeniyle daha sonralari yeni karbamat esterleri gelistirilmeye baslanmistir. Gunumuzde kullanimda olan 200 farkli organofosfatli insektisit ve 25 kadar karbamat grubu insektisit bulunmaktadir. Organofosfatli insektisitler, fosforik asit veya GIRIS INSEKTISIT ZEHIRLENMELERI birlikte, Turkiye’de esas olarak veterinerlikte kullanilan bir ilac olmasina karsin, insektisit olarak da bazi urunleri bulunan amitrazla, ozellikle cocukluk caginda zehirlenme olgularina ait cok sayida kayit bulunmasi dikkat cekicidir. Diger taraftan, yasaklanmis organoklorlu bilesiklerle zehirlenme olgularina rastlanmis olmasi da toplumsal ve duzenleyici kuruluslar duzeyinde onlem ve denetimlerin yetersizligini dusundurmektedir. Calismanin son bolumunde, ulkemizde insektisitlerin tarimsal uretim, saklama ya da istemli veya diger sekillerde tuketimleri ile ilgili olarak ortaya cikan sonuclar ve bu urunlerin dogru ve guvenli uretimi ve tuketimine yonelik olarak ve zehirlenmelere karsi alinmasi gereken onlemlere iliskin oneriler siralanmistir. Anahtar Kelimeler: Insektisit, organofosfatli insektisitler, organoklorlu insektisitler, piretroidler, insektisit zehirlenmeleri countries. On the other hand, poisoning cases with banned organochlorine insecticides have been thought to be caused by the insufficiency of necessary measures and controls that have not been taken by regulatory authorities and manufacturers. The conclusions on consumption of insecticides in agricultural production, storing, and intentional or other modes, and recommendations on the correct and safe production and use of insecticides, along with the protective measures to be taken against poisonings with these compounds, were listed in the last part of the review.

The objective of this study was to investigate the effects of iodine (I(2)) and/or selenium (Se) deficiency on thyroid hormones and hepatic xenobiotic metabolizing enzyme systems using a triple animal model. Three-week-old male Wistar rats were fed for seven weeks. Se deficiency was introduced by a diet containing

This study aimed to investigate the effects of di(2-ethylhexyl)phthalate (DEHP) on Sertoli-cell vimentin filaments and germ-cell apoptosis in testes of pubertal rats at different selenium (Se) status. Se deficiency was produced in 3-weeks old Sprague-Dawley rats by feeding them ≤0.05 Se mg/kg diet for 5 weeks, Se supplementation group was on 1 mg Se/kg diet, and DEHP was applied at 1000 mg/kg dose by gavage during the last 10 days of the feeding period. The diet with excess Se did not cause any appreciable alteration in vimentin staining and apoptosis of germ cells, but Se deficiency caused a mild decrease in the intensity of vimentin immunoreactivity and enhanced germ-cell apoptosis significantly (approximately 3-fold, p

Di(ethylhexyl)phthalate (DEHP), the most widely used plasticizer, was investigated to determine whether an oxidative stress process was one of the underlying mechanisms for its testicular toxicity potential. To evaluate the effects of selenium (Se), status on the toxicity of DEHP was further objective of this study, as Se is known to play a critical role in testis and in the modulation of intracellular redox equilibrium. Se deficiency was produced in 3-weeks-old Sprague-Dawley rats feeding them ≤0.05 mg Se /kg diet for 5 weeks, and Se-supplementation group was on 1 mg Se/kg diet. DEHP-treated groups received 1000 mg/kg dose by gavage during the last 10 days of the feeding period. Activities of antioxidant selenoenzymes [glutathione peroxidase 1 (GPx1), glutathione peroxidase 4 (GPx4), thioredoxin reductase (TrxR)], catalase (CAT), superoxide dismutase (SOD), and glutathione S-transferase (GST); concentrations of reduced glutathione (GSH), oxidized glutathione (GSSG), and thus the GSH/GSSG redox ratio; and thiobarbituric acid reactive substance (TBARS) levels were measured. DEHP was found to induce oxidative stress in rat testis, as evidenced by significant decrease in GSH/GSSG redox ratio (>10-fold) and marked increase in TBARS levels, and its effects were more pronounced in Se-deficient rats with ∼18.5-fold decrease in GSH/GSSG redox ratio and a significant decrease in GPx4 activity, whereas Se supplementation was protective by providing substantial elevation of redox ratio and reducing the lipid peroxidation. These findings emphasized the critical role of Se as an effective redox regulator and the importance of Se status in protecting testicular tissue from the oxidant stressor activity of DEHP.

Ozet Amac: Bu calismanin amaci endokrin bozucu etkileri bilinen di 2 etilhekzil fitalat DEHP ve metaboliti mono 2 etilhekzil fitalat nbsp; MEHP plazma duzeylerinin yuksek oldugu belirlenen pubertal jinekomasti hastalarinda plazma fitalat duzeyleri ile pankreatik lipaz ve a amilaz duzeyleri arasindaki iliskinin incelenmesi ve fitalatlarin pankreas uzerindeki olasi etkilerinin degerlendirilmesidir Gerec ve Yontem: Calisma grubu 40 pubertal jinekomasti hastasindan olusmaktadir Plazma fitalat duzeyleri DEHP ve MEHP mono 2 etikhekzil Yuksek basincli sivi kromatografisi high pressure liquid chromatography kullanilarak belirlenmistir Lipaz ve a amilaz duzeyleri enzimatik kolorimetrik yontemle olculmustur Incelenen degiskenler arasindaki iliski iliski katsayisi saptanarak incelenmistir Bulgular: Jinekomasti hastalarindaki plazma DEHP ve MEHP duzeyleri kontrol grubuna oranla onemli duzeyde yuksek bulunmustur Alfa amilaz ve MEHP duzeyleri arasinda jinekomasti hastalarinda r= 0 388 p lt;0 05 ve tum calisma grubunda r= 0 353 p lt;0 05 negatif iliski saptanmistir DEHP ve a amilaz duzeyleri arasinda da tum calisma grubunda onemli duzeyde negatif iliski r= 0 323 p lt;0 05 saptanmistir Cikarimlar: Sonuclar fitalat varliginin a amilaz salgilanmasinda belirgin azalmalara neden olabilecegine isaret etmektedir Gozlenen bu ters iliski fitalatlarin PPARg peroxisome proliferator activated receptor gamma etkinligi ile aciklanabilir nbsp; Turk Ped Ars 2010; 45: 366 70 Anahtar sozcukler: a amilaz di 2 etilhekzil fitalat jinekomasti lipaz mono 2 etilhekzil fitalat nbsp

OBJECTIVE: Several untoward health effects of phthalates, which are a group of industrial chemicals with many commercial uses including personal-care products and plastic materials, have been defined. The most commonly used, di-(2-ethylhexyl)-phthalate (DEHP), is known to have antiandrogenic or estrogenic effects or both. Mono-(2-ethylhexyl)-phthalate (MEHP) is the main metabolite of DEHP. In this study, we aimed to determine the plasma DEHP and MEHP levels in pubertal gynecomastia cases. PATIENTS AND METHODS: The study group comprised 40 newly diagnosed pubertal gynecomastia cases who were admitted to Hacettepe University Ihsan Doğramacı Children's Hospital. The control group comprised 21 age-matched children without gynecomastia or other endocrinologic disorder. Plasma DEHP and MEHP levels were measured by using high-performance liquid chromatography. Serum hormone levels were determined in some pubertal gynecomastia cases according to the physician's evaluation. RESULTS: Plasma DEHP and MEHP levels were found to be statistically significantly higher in the pubertal gynecomastia group compared with the control group (P < .001) (DEHP, 4.66 ± 1.58 and 3.09 ± 0.90 μg/mL, respectively [odds ratio: 2.77 (95% confidence interval: 1.48–5.21)]; MEHP, 3.19 ± 1.41 and 1.37 ± 0.36 μg/mL [odds ratio: 24.76 (95% confidence interval: 3.5–172.6)]). There was a statistically significant correlation between plasma DEHP and MEHP levels (r: 0.58; P < .001). In the pubertal gynecomastia group, no correlation could be determined between plasma DEHP and MEHP levels and any of the hormone levels. CONCLUSIONS: DEHP, which has antiandrogenic or estrogenic effects, may be an etiologic factor in pubertal gynecomastia. These results may pioneer larger-scale studies on the etiologic role of DEHP in pubertal gynecomastia.

Considering the potential adverse effects of selenium and iodine deficiencies, and taking into account the widespread but often careless use of pyrethroid insecticides and their possible endocrine-disrupting effects, this study was undertaken to investigate the effects of fenvalerate on thyroid hormone parameters in both healthy and selenium- and/or iodine-deficient rats. Fenvalerate exposure had no effect on the TT4 levels of healthy controls but caused significant increases both in iodine deficiency (ID) and selenium plus iodine deficiency (ISeD), and a significant decrease in selenium deficiency (SeD). Dramatic increases in TT3 of all groups were observed by fenvalerate. Moreover, it caused insignificant decrease of thyroid stimulating hormone in healthy controls, no effect in SeD, and significant elevation in ID and ISeD. These results, thus, showed that the widely used pyrethroid insecticide fenvalerate has the potential to change significantly thyroid hormone parameters both in normal and deficiency states, and consequences of its thyroid status modifying effect might be of critical importance particularly in sensitive individuals and patients with thyroid dysfunction.

Aflatoxins (AFs), the secondary metabolites produced by species of Aspergilli , specifically Aspergillus flavus and Aspergillus parasiticus , have harmful effects on humans, animals, and crops that result in illnesses and economic losses. Wheat that is susceptible to these fungi infections through its growth, harvest, transport, and storage, is the most important staple food in Turkey. Therefore, this study has been undertaken to determine the AFB 1 , AFB 2 , AFG 1 , AFG 2 levels by HPLC in forty-one wheat samples grown and consumed in some regions of Turkey. The concentrations of total AFs in the wheat samples were determined to be ranging from 10.4 to 643.5 ng/kg. Fiftynine percent of the samples were found to be positive for total AFs. The percentage of positive samples for AFB 1 , AFB 2 , AFG 1 , and AFG 2 were 42, 12, 37, and 12%, respectively. Although the detected levels are under the permitted levels for AFs in cereals, these amounts should be considered in regard to overall daily exposure to mycotoxins.

Measured (n = 36, 51 ·g/day) and estimated (n = 274, 44 ·g/day) dietary daily intake of selenium in Turkey is low compared to the RDA value of 55 ·g Se/day. When the existence of high prevalence of iodine deficiency in most part of the country is considered, adequate level of dietary Se becomes more important. We have found recently that high iodine-deficient goitrous children had lower Se levels and antioxidant enzyme (AOE) activities, and higher levels of DNA base lesions than non-goitrous controls.

Iodine and selenium are essential components of normal thyroid hormone metabolism and are involved in the modulation of antioxidant defense system. This study was designed to evaluate the extent of peroxidation of lipids and activities of antioxidant enzymes (AOEs) in various tissues of iodine- and/or selenium-deficient rats in relation to thyroid hormone metabolism. Iodine deficiency caused marked enhancements in glutathione peroxidase (GSHPx), superoxide dismutase (SOD), and catalase (CAT) activities in thyroid but did not cause lipid peroxidation (LP), indicating the occurrence of an adaptive response that protected the gland against oxidative stress induced by high levels of thyroid stimulating hormone (TSH). Except significant reduction in CAT activity in liver and kidney and an enhancement of SOD in kidney, iodine deficiency did not cause any other alterations in other tissues. Selenium deficiency and combined iodine and selenium deficiency caused significant alterations in AOE activities in all tissues and caused significantly high levels of LP in thyroid, liver, brain, and plasma, but not in kidney. Alterations in selenium-involved deficiencies appeared to be mainly caused by substantial losses of GSHPx activity; however, compensatory changes in SOD and CAT activities were also observed. J. Trace Elem. Exp. Med. 17:109–121, 2004. © 2004 Wiley-Liss, Inc.

Background: This study has been undertaken to investigate the possible alterations of oxidant/antioxidant status in uremic patients undergoing hemodialysis (HD) and the effects of vitamin E supplementation. Methods: Erythrocyte antioxidant enzyme activities [glutathione peroxidase (GSHPx), superoxide dismutase (SOD) and catalase (CAT)] and thiobarbituric acid reactive substance (TBARS) concentrations as a measure of lipid peroxidation in HD patients have been determined and compared with healthy controls. The patient group consisted of 36 uremic patients 21-75 years of age undergoing maintenance HD three times weekly for an average of 41 months. The efficiency of Vitamin E therapy in dialysis patients was also assessed by re-evaluating antioxidant status of the same patients after supplementation of the vitamin E in a dosage of 600 mg/daily for 14 weeks. Results: A significant decrease in the activities of erythrocyte SOD, CAT and GSHPx and a significant increase in TBARS concentrations were found in patient group compared to control group (p < 0.001). A significant correlation between GSHPx activities and duration of HD therapy was also observed (r= - 0.46,p < 0.01). Vitamin E supplementation caused an increase in GSHPx and SOD activities and a decrease in TBARS concentrations. A slight but not significant increase in CAT activity was also observed by Vitamin E. Conclusions: The results suggest the presence of an oxidative activity and the possible preventive role of Vitamin E therapy in uremic patients undergoing HD. (C) 2003 Elsevier B.V. All rights reserved.

Tissue distribution of Fe, Mn, Cu, and Zn, the essential trace elements associated with oxidant and/or antioxidant processes, was examined in iodine- and/or selenium-deficient rats (ID, SeD, ISeD). Fe and Mn were the most affected minerals in all types of deficiency states. Mn levels decreased significantly in the liver in all deficiency states (approx 20-30%), in the heart in ID and SeD rats (approx 30-35%) and in the testis in ID rats (approx 15%). Whereas Mn enhancement was noted in kidney (approx 45%) and plasma in SeD and ISeD (approx 20% and 50%, respectively) animals. However, most striking alterations were seen with Fe. Significant elevation of Fe concentrations were observed in all deficiency states in the kidney (approx 90-125%) and heart (approx 20-25%), and in the liver in SeD (approx 35%) and ISeD (approx 75%) rats, whereas significant (approx 20%) Fe enhancement in the testis was observed only in ISeD animals. Lower Cu (approx 10-15%) and higher Zn (approx 10-20%) concentrations in heart tissues in all deficiency states were found; higher Zn (approx 20-35%) in the kidney of SeD and ISeD rats, and lower Cu in the testis of SeD animals were observed. In brain tissue, no alteration was seen in Fe, Mn, and Zn content, however, significantly increased (approx 15-20%) Cu concentrations were noted in all deficiency states. The results of this study indicated that iodine and/or selenium deficiency may modify the distribution and the homeostasis of other minerals.

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.

International audience; This study was performed to determine the hepatotoxicity of di(2‐ethylhexyl)phthalate (DEHP) in relation to selenium status. In 3‐week‐old Sprague‐Dawley rats, selenium deficiency was induced by a ≤0.05 selenium mg/kg. A selenium supplementation group was given 1 mg selenium/kg diet for 5 weeks. Di(2‐ethylhexyl)phthalate‐treated groups received 1000 mg/kg dose by gavage during the last 10 days of the experiment. Histopathology, peroxisome proliferation, catalase (CAT) immunoreactivity and activity and apoptosis were assessed. Activities of antioxidant selenoenzymes [glutathione peroxidase 1 (GPx1), glutathione peroxidase 4 (GPx4), thioredoxin reductase (TrxR1)], superoxide dismutase (SOD), and glutathione S‐transferase (GST); aminotransferase, total glutathione (tGSH), and lipid peroxidation (LP) levels were measured. Di(2‐ethylhexyl)phthalate caused cellular disorganization while necrosis and inflammatory cell infiltration were observed in Se‐deficient DEHP group (DEHP/SeD). Catalase activity and immunoreactivity were increased in all DEHP‐treated groups. Glutathione peroxidase 1 and GPx4 activities decreased significantly in DEHP and DEHP/SeD groups, while GST activities decreased in all DEHP‐exposed groups. Thioredoxin reductase activity increased in DEHP and DEHP/SeS, while total SOD activities increased in all DEHP‐treated groups. Lipid peroxidation levels increased significantly in SeD (26%), DEHP (38%) and DEHP/SeD (71%) groups. Selenium supplementation partially ameliorated DEHP‐induced hepatotoxicity; while in DEHP/SeD group, drastic changes in hepatic histopathology and oxidative stress parameters were observed.

Ochratoxin A (OTA), one of the most prevalent mycotoxins in the world, has nephrotoxic and hepatotoxic properties. Lycopene is an important carotenoid and has a high singlet-oxygen and free-radical scavenging capacity. This study was designed to investigate the possible protective effects of lycopene against the genotoxicity of OTA in rat tissues using the alkaline comet assay. Male Sprague-Dawley rats were used in the experiments. OTA (0.5 mg/kg b.w./day) was administered by gavage for 14 days, whereas lycopene was applied on the last 7 days or for 14 days of the feeding period, with OTA treatment. OTA caused marked increases in tail length, tail moment, and tail intensity vs. control both in the kidney and liver cells, but not in the lymphocytes. Lycopene administration alone for 7 and 14 days did not provide any significant change in DNA damage of the lymphocytes, renal and hepatic cells vs. controls. However, lycopene for both 7 and 14 days, with OTA exposure in renal and hepatic cells, supplied significant decreases in tail length, tail moment, and tail intensity vs. OTA-exposed rats. The effect of 14 days supplementation seemed to be more protective, particularly against hepatic cells. These results suggest that lycopene may protect hepatic and renal tissue from OTA-induced DNA damage.

International audience; This study was designed to examine the oxidative stress potential of di(2-ethylhexyl)phthalate (DEHP) on rat kidney and to evaluate possible protective effect of selenium (Se) status. Se deficiency (SeD) was produced in 3-week old Sprague-Dawley rats by feeding them ≤ 0.05 Se mg/kg diet for 5 weeks; Se supplementation group (SeS) was on 1 mg Se/kg diet. DEHP treated groups received 1000 mg/kg dose by gavage during the last 10 days of the feeding period. Activities of antioxidant selenoenzymes [glutathione peroxidase 1 (GPx1), glutathione peroxidase 4 (GPx4), thioredoxin reductase (TrxR)], catalase (CAT), superoxide dismutase (SOD), and glutathione S-transferase (GST); concentrations of total glutathione (GSH), thiols and thiobarbituric acid reactive substance (TBARS) levels were measured. DEHP treatment was found to induce oxidative stress in rat kidney, as evidenced by significant decreases in GPx1 (~20%) and SOD (~30%) activities and GSH levels (~20%), along with marked decrease in thiol content (~40%) and increase in TBARS (~30%) levels. The effects of DEHP was more pronounced in SeD rats, whereas Se supplementation was protective by providing substantial elevations of GPx1 and GPx4 activities and GSH levels. These findings emphasized the critical role of Se as an effective redox regulator and the importance of Se status in protecting renal tissue from the oxidant stressor activity of DEHP.

The Two Faces of Endocrine Disrupting Chemicals and Genital Development Endocrine-Disrupting Chemicals (EDCs) are substances that interfere with hormone biosynthesis, metabolism, or action resulting in a deviation from normal homeostatic control or reproduction. EDCs represent a broad class of molecules in our environment, food, and consumer products such as plasticizers, polychlorinated biphenyls, organochlorinated pesticides, and many other chemicals. Most of the products that contain these EDCs are requisitely used in everyday life; however the results of several animal models and human clinical research, as well as data from epidemiological studies reveal that EDCs are a significant concern to public health.

Unpredictable Effects of Chemical Mixtures on Liver in Health and Disease Liver is the primary organ for the detoxification, as well as being the target of many of environmental chemicals. Today, we are all exposed to mixtures of different chemicals at a time because of industrialization and fast life style. Other than environmental chemicals, many people are subject to a mixture of drugs. For example, patients of complex diseases receive an average of six drugs at time when hospitalized. Home influenza treatment consists of analgesics, antihistaminics, and cough syrups. Yet, exposure to an antioxidant and chemical/drug together might be hepatotoxic, if the antioxidant is not applied at a proper dosage or if they affect the same enzymes, receptors, or pathways. Even drinking water may contain residues of pesticides, Polychlorinated Biphenyls (PCBs) along with heavy metals, which all possess hepatic toxicity potential. Exposure to different xenobiotics or administration of several drugs at a time may change the effect of each single component or may affect course of a disease.

International audience; Di(ethylhexyl)phthalate (DEHP), the most widely used plasticizer, was investigated to determine whether an oxidative stress process was one of the underlying mechanisms for its testicular toxicity potential. To evaluate the effects of selenium (Se), status on the toxicity of DEHP was further objective of this study, as Se is known to play a critical role in testis and in the modulation of intracellular redox equilibrium. Se deficiency was produced in 3-weeks-old Sprague-Dawley rats feeding them ≤0.05 mg Se /kg diet for 5 weeks, and Se-supplementation group was on 1 mg Se/kg diet. DEHP-treated groups received 1000 mg/kg dose by gavage during the last 10 days of the feeding period. Activities of antioxidant selenoenzymes [glutathione peroxidase 1 (GPx1), glutathione peroxidase 4 (GPx4), thioredoxin reductase (TrxR)], catalase (CAT), superoxide dismutase (SOD), and glutathione S-transferase (GST); concentrations of reduced glutathione (GSH), oxidized glutathione (GSSG), and thus the GSH/GSSG redox ratio; and thiobarbituric acid reactive substance (TBARS) levels were measured. DEHP was found to induce oxidative stress in rat testis, as evidenced by significant decrease in GSH/GSSG redox ratio (>10-fold) and marked increase in TBARS levels, and its effects were more pronounced in Se-deficient rats with ∼18.5-fold decrease in GSH/GSSG redox ratio and a significant decrease in GPx4 activity, whereas Se supplementation was protective by providing substantial elevation of redox ratio and reducing the lipid peroxidation. These findings emphasized the critical role of Se as an effective redox regulator and the importance of Se status in protecting testicular tissue from the oxidant stressor activity of DEHP. © 2011 Wiley Periodicals, Inc. Environ Toxicol, 2011.

International audience; Phthalates are abundantly produced plasticizers, and di(ethylhexyl) phthalate (DEHP) is the most widely used derivative in various consumer products and medical devices. Animal studies show that DEHP and various other phthalates cause reproductive and developmental toxicity. Although the evidences are limited, it seems reasonable that DEHP may have a potential for similar adverse effects in humans. Such concerns are increasing, particularly for the developing reproductive system of male infants and children. By taking into account the essentiality of selenium (Se) in testicular structure and functions and the high prevalence of inadequate Se intake in various part of the world, this study was designed to investigate the testicular toxicity of DEHP in Se-deficient male rats and to examine the possible preventive effects of Se supplementation on phthalate toxicity. Se deficiency was generated by feeding 3-week-old Sprague-Dawley rats with a ≤0.05 Se mg/kg diet for 5 weeks. Supplementation groups were on a 1 mg Se/kg diet, and DEHP-treated groups received a 1,000 mg/kg dose by gavage during the last 10 days of the feeding period. Testicular histopathology, sperm count and motility, and sperm morphology were examined, and plasma levels of sex hormones were measured. Toxicity and antiandrogenic effects of DEHP were evidenced by disturbed testicular histology and spermatogenesis, diminished testosterone, leutinizing hormone (LH) and follicle stimulating hormone (FSH) levels, and sperm motility. The effects of DEHP were much more pronounced in Se-deficient rats, whereas Se supplementation was found to be protective, reflecting its regulating role in cellular redox equilibrium.

Considering the potential adverse effects of selenium and iodine deficiencies, and frequency of intensive but improper use of insecticides, this study was designed to evaluate the effects of a pyrethroid insecticide, fenvalerate, on the oxidant/antioxidant status of liver using a rat model of iodine and/or selenium deficiency. The study was conducted on eight groups of 3-week old Wistar rats. Iodine and/or selenium deficiency was introduced by feeding the animals with a diet containing

Di(2-ethylhexyl)-phthalate (DEHP) is the most abundantly used phthalate derivative, inevitable environmental exposure of which is suspected to contribute to the increasing incidence of testicular dysgenesis syndrome in humans. Oxidative stress and mitochondrial dysfunction in germ cells are suggested to contribute to phthalate-induced disruption of spermatogenesis in rodents, and Leydig cells are one of the main targets of phthalates' testicular toxicity. Selenium is known to be involved in the modulation of intracellular redox equilibrium, and plays a critical role in testis, sperm, and reproduction. This study was aimed to investigate the oxidative stress potential of DEHP and its consequences in testicular cells, and examine the possible protective effects of selenium using the MA-10 mouse Leydig tumor cell line as a model. In the presence and absence of selenium compounds [30 nM sodium selenite (SS), and 10 mu M selenomethionine (SM)], the effects of exposure to DEHP and its main metabolite mono(2-ethylhexyl)phthalate (MEHP) on the cell viability, enzymatic and non-enzymatic antioxidant status, ROS production, p53 expression, and DNA damage by alkaline Comet assay were investigated. The overall results of this study demonstrated the cytotoxicity and genotoxicity potential of DEHP, where MEHP was found to be more potent than the parent compound. SS and SM produced almost the same level of protection against antioxidant status modifying effects, ROS and p53 inducing potentials, and DNA damaging effects of the two phthalate derivatives. It was thus shown that DEHP produced oxidative stress in MA-10 cells, and selenium supplementation appeared to be an effective redox regulator in the experimental conditions used in this study, emphasizing the critical importance of the appropriate selenium status. (C) 2010 Elsevier Inc. All rights reserved.

Importance of iodine and selenium in thyroid metabolism is well known, but the roles of other essential trace elements including copper, zinc, manganese and iron on thyroid hormone homeostasis remain unclear. The aim of this study was to investigate the status of those trace elements in benign thyroid diseases and evaluate possible links between trace element concentrations and thyroid hormones. The study group was composed of 25 patients with multinodular goiter. Concentrations of thyroid hormones (plasma-free thyroxine, FT(4); free triiodothyronine, FT(3); and thyrotropin, TSH), selenium, copper, zinc, manganese and iron in plasma, and urinary iodine were determined. The results were compared with those of a healthy control group (n=20) with no thyroid disorder. A mild iodine deficiency was observed in the patients with multinodular goiter whereas urinary iodine levels were in the range of "normal" values in healthy controls. All patients were euthyroid, and their thyroid hormone concentrations were not significantly different from the control group. Plasma selenium, zinc and iron concentrations did not differ from controls, while copper and manganese levels were found to be significantly higher in the patients with multinodular goiter indicating links between these trace elements and thyroid function and possibly in development of goiter. Besides iodine, there was a significant correlation between plasma copper concentration and FT(3)/FT(4) ratio.

Forty-seven samples of corn were collected from various street bazaars and market outlets in different regions of Turkey and total aflatoxin (AF) and ochratoxin A (OTA) levels were determined by enzyme-linked immunosorbent assay (ELISA) following sample preparation. Levels of AF and OTA in corn samples ranged between 1.75-120.3 μg/kg and 1.08-8.57 μg/kg, respectively. Although 53% of the samples analysed had no detectable levels of AF, 4% of similar samples were found to contain AFs above the acceptable limit of 10 μg/kg in Turkey. For OTA, 4% of the corn samples had levels above the acceptable limit (3 μg/kg) in Turkey, with over 43% samples not found to contain this mycotoxin. Although the levels of mycotoxins analysed in this study were not found to be high and the percentage of samples contaminated above permitted limits were low, the importance of overall daily dietary intake should not be underestimated and control of these fungal metabolites in corn must be explored to minimise the hazards they may cause in humans.

This study has been undertaken to investigate the regional and seasonal variability in ochratoxin A (OTA) exposure of healthy population living in Black Sea and Mediterranean regions of Turkey by measuring serum OTA concentrations. The mean serum concentrations of OTA were determined to be 0.137 ng/mL (0.0306-0.887 ng/mL) and 0.312 ng/mL (0.028-1.496 ng/mL) in all samples for winter and summer, respectively by enzyme-linked immunosorbent assay (ELISA). The differences between mean values of OTA in all serum samples collected in summer and winter were statistically significant. The highest OTA concentration was determined in the children living in Black Sea Region in summer. The mean daily intake levels of OTA in all samples were estimated as 0.182 ng/kg b.w./day and 0.408 ng/kg b.w./day in winter and summer, respectively. The results showed that the mean serum concentrations of OTA in healthy population in both regions were found not to be exceeded 1 ng/mL in agreement with the distribution reported in most European countries and that the daily intake levels of OTA were calculated below the tolerable daily intake levels given by regulatory authorities. However, overall results suggest that Turkish population living in these regions is continuously exposed to OTA and that the exposure levels are also elevated in summer period compared to winter.

In order to investigate the relations of iodine deficiency and/or goiter with selenium (Se) and antioxidant enzyme (AOE) status, we determined the relevant parameters of goitrous high school children living in an endemic goiter area of Turkey. Subjects were selected by a simple random sampling technique after screening the whole population of the high schools of two towns by neck palpation. The results of the goitrous group (n = 48, aged 15-18 yr) were compared with those of nongoitrous control children (n = 49) from the same populations, and with an outside control group (n = 24) from a lower-goiter-prevalence area. The overall prevalence of goiter was 39.6% in the high school population of the area. Activities of erythrocyte AOE (glutathion peroxidase, catalase, and superoxide dismutase) and concentrations of plasma and erythrocyte Se and urinary iodine were found to be significantly lower in goitrous children than both in-region and out-region of the control groups. When the whole study group was reclassified according to the severity of iodine deficiency, it was found that the AOE and Se status of those control children without goiter but with high iodine deficiency was significantly higher than goitrous children, although they did not differ from nondeficient control group. This might be the result of the possibility that goitrous children are exposed of oxidative stress, which may introduce alterations to the antioxidant defense system and/or the antioxidant status is relatively lower in goitrous children than those children who are highly iodine-deficient but did not develop goiter. The results of this study seem to support the view that the risk of goiter development may be higher in highly iodine-deficient children with lower enzymatic antioxidant and Se status.

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.