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.

Renal changes and apoptosis caused by subacute exposure to Aroclor 1254 in selenium-deficient and selenium-supplemented rats.

Aroclor 1254 (A1254), a mixture of polychlorinated biphenyls, exerts hepatic, renal, and reproductive toxicity in rodents. This study aimed to determine a protective role of selenium on histopathological changes, oxidative stress, and apoptosis caused by A1254 in rat kidney. It included a control group, which received regular diet containing 0.15 mg/kg Se (C), a Se-supplemented group (SeS) receiving 1 mg/kg Se, a Se-deficient group (SeD) receiving Se-deficient diet of ≤0.05 mg/kg Se, an A1254-treated group (A) receiving 10 mg/kg of Aroclor 1254 and regular diet, an A1254-treated group receiving Se-supplementation (ASeS), and an A1254-treated group receiving Se-deficient diet (ASeD). Treatments lasted 15 days. After 24 h of the last dose of A1254, the animals were decapitated under anaesthesia and their renal antioxidant enzyme activities, lipid peroxidation (LP), glutathione, protein oxidation, and total antioxidant capacity levels measured. Histopathological changes were evaluated by light and electron microscopy. Apoptosis was detected with the TUNEL assay. Kidney weights, CAT activities, and GSH levels decreased significantly in all A1254-treated groups. Renal atrophic changes and higher apoptotic cell counts were observed in the A and ASeD groups. Both groups also showed a significant drop in GPx1 activities (A - 34.92 % and ASeD - 86.46 %) and rise in LP (A - 30.45 % and ASeD - 20.44 %) vs control. In contrast, LP levels and apoptotic cell counts were significantly lower in the ASeS group vs the A group. Histopathological changes and renal apoptosis were particularly visible in the ASeD group. Our findings suggest that selenium supplementation provides partial protection against renal toxicity of Aroclor 1254.

Oxidative Stress Parameters, Selenium Levels, DNA Damage, and Phthalate Levels in Plastic Workers.

Di(2-ethylhexyl)phthalate (DEHP) is the most widely used phthalate. DEHP is highly used in PVC floorings and PVC windows and carpeting. The objective of this study was to determine sex hormone levels, oxidative stress parameters, selenium levels, DNA damage, and phthalate levels in plastics workers (n = 24, age = 20-58 years) working in the production of rubber mechanical goods and exposed to DEHP in workplace. The control group (n = 29, age = 25-54, all male) was selected from age-matched healthy adults. Antioxidant parameters and DNA damage were determined by spectrophotometry. Selenium levels were determined by atomic absorption spectroscopy. Plasma hormone levels were measured by chemiluminescence microparticle immunoassay. Plasma phthalate levels were determined by high-pressure liquid chromatography. Plastic workers had lower serum testosterone and free T4 levels and higher follicle-stimulating hormone levels vs. controls. Liver enzyme activities were markedly higher in workers vs. controls. There were also increases in plasma glutathione peroxidase levels and marked decreases in plasma selenium and erythrocyte total glutathione levels in plastics workers (P < 0.05 vs. control). Plasma 8-hydroxy-2'-deoxyguanosine levels were 14-fold higher in plastics workers than in controls. Plasma DEHP and mono(2-ethylhexyl)phthalate were also markedly higher in workers vs. controls. The results of this study show that occupational exposure to DEHP may lead to disturbances in sex hormones, increased liver problems, higher oxidative stress and DNA damage levels, and lower trace element concentrations in workers. More comprehensive and mechanistic studies with higher numbers of subjects are needed to show the unwanted effects of occupational exposure to DEHP.

Antioxidants and selenocompounds inhibit 3,5-dimethylaminophenol toxicity to human urothelial cells.

Exposure to alkyl anilines may lead to bladder cancer, which is the second most frequent cancer of the urogenital tract. 3,5-dimethylaniline is highly used in industry. Studies on its primary metabolite 3,5-dimethylaminophenol (3,5-DMAP) showed that this compound causes oxidative stress, changes antioxidant enzyme activities, and leads to death of different mammalian cells. However, there is no in vitro study to show the direct effects of 3,5-DMAP on human bladder and urothelial cells. Selenocompounds are suggested to decrease oxidative stress caused by some chemicals, and selenium supplementation was shown to reduce the risk of bladder cancer. The main aim of this study was to investigate whether selenocompounds organic selenomethionine (SM, 10 µmol/L) or inorganic sodium selenite (SS, 30 nmol/L) could reduce oxidative stress, DNA damage, and apoptosis in UROtsa cells exposed to 3,5-DMAP. 3,5-DMAP caused a dose-dependent increase in intracellular generation of reactive oxygen species, and its dose of 50 µmol/L caused lipid peroxidation, protein oxidation, and changes in antioxidant enzyme activities in different cellular fractions. The comet assay also showed single-strand DNA breaks induced by the 3,5-DMAP dose of 50 µmol/L, but no changes in double-strand DNA breaks. Apoptosis was also triggered. Both selenocompounds provided partial protection against the cellular toxicity of 3,5-DMAP. Low selenium status along with exposure to alkyl anilines can be a major factor in the development of bladder cancer. More mechanistic studies are needed to specify the role of selenium in bladder cancer.

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.

Lycopene restores trace element levels in ochratoxin A-treated rats.

This study was designed to investigate the in vivo effects of ochratoxin A (OTA) and/or lycopene on the levels of selenium, zinc, and copper in the liver, kidneys, and testes of male Sprague-Dawley rats. The rats were treated with OTA (0.5 mg kg-1 day-1) and/or lycopene (5 mg kg-1 day-1) by gavage for 7 or 14 days. Trace element levels were measured by atomic absorption spectrometry. OTA significantly lowered selenium (20 % in the liver, 17 % in the kidney, and 40 % in the testis), zinc (24 % in the liver, 23 % in the kidney, and 26 % in the testis), and copper levels (40 % in the liver and 10 % in the kidney). Lycopene alone did not affect the trace element levels in any of the organs. In combination with OTA, however, it significantly restored liver, kidney, and testis selenium and zinc levels compared to the group treated with OTA alone. Our results have confirmed that depletion of trace elements in different organs is one of the mechanisms of action of OTA. They also suggest that lycopene interferes with this depleting effect and restores trace element levels, the implications of which need to be further investigated.

The effects of fenvalerate on hepatic and cerebral xenobiotic metabolizing enzymes in selenium and/or iodine deficient rats.

OBJECTIVES: Particularly in developing countries, selenium and/or iodine deficiencies are encountered and use of pesticides in agriculture are not well-controlled. Fenvalerate is a pyrethroid insectide used in agriculture and has applications against a wide range of pests. This study was designed to evaluate the effects of fenvalerate on hepatic and cerebral xenobiotic metabolizing enzyme activities in the presence of iodine and/or selenium deficiency on a rat model. MATERIALS AND METHODS: Iodine and/or selenium deficiency was induced by feeding three-week-old Wistar rats with a diet containing <0.005 mg selenium kg-1, and/or administering 1% sodium perchlorate in drinking water for 7 weeks. Test groups received fenvalerate (100 mg kg-1 BW IP) for the last 7 days. Hepatic and cerebral microsomal aniline hydroxylase (CYP2E1) and cytosolic glutathione S-transferase (GST) activities were determined. Besides, hepatic NADPH-cytochrome P450 reductase (P450R), ethoxyresorufin O-deethylase (EROD, CYP1A1/1A2) and penthoxyresorufin O-depenthylase (PROD, CYP2B1/2B2), activities were also measured. RESULTS: Fenvalerate had a general inductive effect on the hepatic and cerebral xenobiotic metabolizing enzyme activities. Moreover, enzyme activities were also altered by iodine and/or selenium deficiency, but the effects seemed to be enzyme- and tissue-specific. CONCLUSION: The inductive effect of fenvalerate, particularly in high dose exposures, may change the metabolism of several xenobiotics, including drugs, as well as endogenous substrates. The effects may vary depending on the selenium and/or iodine status of individual.

Plasma phthalate and bisphenol a levels and oxidant-antioxidant status in autistic children.

Phthalates and bisphenol A (BPA) are endocrine disruting chemicals (EDCs) that are suggested to exert neurotoxic effects. This study aimed to determine plasma phthalates and BPA levels along with oxidant/antioxidant status in autistic children [n=51; including 12 children were diagnosed with "Pervasive Developmental Disorder-Not Otherwise Specified (PDD-NOS)]. Plasma levels of BPA, di (2-ethylhexyl)-phthalate (DEHP) and its main metabolite mono (2-ethylhexyl)-phthalate (MEHP); thiobarbituric acid reactive substance (TBARS) and carbonyl groups; erythrocyte glutathione peroxidase (GPx1), thioredoxin reductase (TrxR), catalase (CAT), superoxide dismutase (SOD) and glutathione reductase (GR) activities and glutathione (GSH) and selenium levels were measured. Plasma BPA levels of children with PDD-NOS were significantly higher than both classic autistic children and controls (n=50). Carbonyl, selenium concentrations and GPx1, SOD and GR activities were higher (p<0.05); CAT activity was markedly lower in study group. BPA exposure might be associated with PDD-NOS. Intracellular imbalance between oxidant and antioxidant status might facilitate its neurotoxicity.

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.

The effects of di(2-ethylhexyl) phthalate and/or selenium on trace element levels in different organs of rats.

Di(2-ethylhexyl)phthalate (DEHP), a widely used plasticizer for synthetic polymers, is known to have endocrine disruptive potential, reproductive toxicity, and induces hepatic carcinogenesis in rodents. Selenium (Se) is a component of several selenoenzymes which are essential for cellular antioxidant defense and for the functions of mammalian reproductive system. The present study was designed to investigate the effects of DEHP exposure on trace element distribution in liver, testis, and kidney tissues and plasma of Se-deficient and Se-supplemented rats. Se deficiency was produced by feeding 3-week old Sprague-Dawley rats with ≤0.05mg Se/kg diet for 5 weeks, and supplementation group were on 1mg Se/kg diet. DEHP treated groups received 1000mg/kg dose by gavage during the last 10 days of feeding period. Se, zinc (Zn), copper (Cu), iron (Fe) and manganese (Mn) levels were measured by inductively coupled plasma mass spectrometry (ICP-MS). Se supplementation caused significant increases in hepatic, renal, and testicular Se levels. With DEHP exposure, plasma Se and Zn, kidney Se, Cu and Mn levels were significantly decreased. Besides, liver Fe decreased markedly in all the DEHP-treated groups. Liver and kidney Mn levels decreased significantly in DEHP/SeD group compared to both DEHP and SeD groups. These results showed the potential of DEHP exposure and/or different Se status to modify the distribution pattern of essential trace elements in various tissues, the importance of which needs to be further evaluated.

A new approach to an old hypothesis; phototherapy does not affect ductal patency via PGE2 and PGI2.

OBJECTIVE: 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. METHODS: Preterm infants whose gestational age<34 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. RESULTS: 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). CONCLUSION: 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.

Cytoplasmic and nuclear toxicity of 3,5-dimethylaminophenol and potential protection by selenocompounds.

Most common alkylanilines in the environment are 2,6-dimethylaniline (2,6-DMA), 3,5-dimethylaniline (3,5-DMA), and 3-ethylaniline (3-EA). 3,5-Dimethylaminophenol (3,5-DMAP), a metabolite of 3,5-DMA, is of particular interest, as it is potentially genotoxic. Supplementation with organic or inorganic forms of selenium (Se) may reduce toxicity following exposure to a wide variety of environmental chemicals. This study was designed to evaluate the protective effects of sodium selenite (SS) and selenomethionine (SM) at varying time points of supplementation (24 h and 72 h) against the cytotoxicity, reactive oxygen species (ROS) production, and genotoxicity of 3,5-DMAP in CHO AS52 cells. 3,5-DMAP caused dose-dependent increase of cytotoxicity, ROS production and genotoxicity, and generated free radicals in the nuclei. Thioredoxin reductase (TrxR), catalase and glutathione reductase activities, and glutathione levels were significantly lower while lipid peroxidation and protein oxidation levels were higher after 3,5-DMAP treatment in both cytoplasm and the nucleus vs. control. After 24 h, both SS and SM provided protection in antioxidant/oxidant status of the 3,5-DMAP-treated cells; however other than supplying higher glutathione peroxidase and TrxR activities, 72 h supplementation did not provide advanced improvement. Selenocompounds may be beneficial against cytotoxic and genotoxic potential of 3,5-DMAP and might protect both nucleus and cytoplasm following exposure to alkylanilines.

The effects of di(2-ethylhexyl)phthalate on rat liver in relation to selenium status.

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.

Effects of di(2-ethylhexyl)phthalate on testicular oxidant/antioxidant status in selenium-deficient and selenium-supplemented rats.

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.

Selenium levels, selenoenzyme activities and oxidant/antioxidant parameters in H1N1-infected children.

Selenium (Se) is an essential trace element, and it shows its biological functions within low molecular Se compounds and Se-containing proteins, known as "selenoproteins". Glutathione peroxidases (GPxs) and thioredoxin reductases (TrxRs) are the most important selenoproteins functioning as antioxidant enzymes. These enzymes protect the body from the endogenous products of cellular metabolism that have been implicated in DNA damage, mutagenesis, and carcinogenesis. H1N1 virus is a subtype of the influenza A virus and was an endemic in humans in 2009 and 2010. Taking into account the high incidence of Se deficiency and the high mortality and morbidity rates in H1N1 infection, this study was designed to investigate the plasma and erythrocyte Se levels, selenoenzyme activities and other oxidant/antioxidant parameters in H1N1-infected children during the 2009-2010 pandemic. We observed a significant increase in C-reactive protein levels (245%) and marked decreases in both plasma and erythrocyte Se levels (11%, both) and in GPx1 (45%), GPx3 (16%) and TrxR (30%) activities in H1N1-infected children compared to the control group. In addition, significant decreases were observed in erythrocyte catalase (CAT) (38%), total superoxide dismutase (SOD) (42%) and glutathione S-transferase (GST) (19%) activities and in erythrocyte total glutathione (GSH) (18%) and plasma GSH (10%) concentrations, while marked increases were observed in plasma lipid peroxidation levels (27%). However, we did not find a significant difference in selenoprotein P (SePP) levels between the groups. Our findings show that Se-dependent and -independent blood redox systems are down-regulated in H1N1 influenza. These findings emphasized the critical role of Se as an effective redox regulator and the importance of Se status in infections, particularly in H1N1 influenza.

The carotenoid lycopene protects rats against DNA damage induced by Ochratoxin A.

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.

Protective effect of lycopene against ochratoxin A induced renal oxidative stress and apoptosis in rats.

This study was designed to investigate the possible protective effect of lycopene against the renal toxic effects of OTA. Male Sprague-Dawley rats (<200 g, n=6) were treated with OTA (0.5 mg/kg/day) and/or lycopene (5 mg/kg/day) by gavage for 14 days. Histopathological examinations were performed and apoptotic cell death in both cortex and medulla was evaluated by TUNEL assay. Besides, biochemical parameters and activities of renal antioxidant selenoenzymes [glutathione peroxidase 1 (GPx1), thioredoxin reductase (TrxR)], catalase (CAT), superoxide dismutase (SOD); concentrations of total glutathione (GSH), and malondialdehyde (MDA) levels were measured. OTA treatment was found to induce oxidative stress in rat kidney, as evidenced by marked decreases in CAT (35%) activity and GSH levels (44%) as well as increase in SOD activity (22%) vs control group. Furthermore, TUNEL analysis revealed a significant increase in the number of TUNEL-positive cells in cortex (49%) and medulla (75%) in OTA administrated group compared to control (p<0.05). Lycopene supplementation with OTA increased GPx1 activity and GSH levels, and decreased apoptotic cell death in both cortex and medulla vs. control. The results of this study showed that at least one of the mechanisms underlying the renal toxicity of OTA is oxidative stress and apoptosis is the major form of cell death caused by OTA. Besides, our data indicate that the natural antioxidant lycopene might be partially protective against OTA-induced nephrotoxicity and oxidative stress in rat.

Thyroidal effects of di-(2-ethylhexyl) phthalate in rats of different selenium status.

This study was designed to investigate the effects of di-(2-ethylhexyl) phthalate (DEHP) on thyroid hormone levels and oxidant/antioxidant parameters in the rat and to evaluate the effects of selenium status. Selenium deficiency was produced by feeding 3-week-old Sprague-Dawley rats with <0.05 mg selenium/kg body weight for 5 weeks, and the supplementation group received a diet of 1 mg selenium/kg body weight. DEHP-treated groups received the compound at a dose of 1000 mg/kg by gavage during the last 10 days of the feeding period. Levels of thyroid hormone levels as well as selenoenzyme (glutathione peroxidase 1, thioredoxin reductase), catalase, and superoxide dismutase (SOD) activity and thiobarbituric acid reactive substance (TBARS) were measured. Total thyroxine (TT4) levels decreased significantly with DEHP exposure (~25%), whereas TT3 level was not altered. The TT4 lowering effect of DEHP exposure was not affected by selenium deficiency but was observed when animals exposed to DEHP received a selenium supplement. DEHP was found to alter the antioxidant status and induce oxidative stress in rat thyroid by increasing SOD activity (~30%) and TBARS levels (~35%). The effects of DEHP were much more pronounced in selenium-deficient rats, as evidenced by significant increases in SOD activity (~65%) and TBARS levels (~55%) compared with the control levels. Thus, these results show the thyroid-disrupting effect of DEHP in rats and protection by selenium.

Di(2-ethylhexyl)phthalate-induced renal oxidative stress in rats and protective effect of selenium.

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.

Selenium and/or iodine deficiency alters hepatic xenobiotic metabolizing enzyme activities in rats.

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 <0.005 mg/kg Se, and I(2) deficiency was produced by sodium perchlorate containing drinking water. The levels of plasma thyroid hormones [total T(4) (TT(4)), total T(3) (TT(3))], thyroid stimulating hormone (TSH); total microsomal cytochrome P450 (CYP450) and cytochrome b5 (CYP b5) levels; activities of microsomal NADPH-cytochrome P450 reductase (P450R), microsomal aniline hydroxylase (CYP2E1), microsomal 7-ethoxyresorufin O-deethylase (EROD), microsomal 7-pentoxyresorufin O-depentylase (PROD) and cytosolic glutathione S-transferase (GST) were determined. In I(2) deficiency total CYP450 levels, activities of CYP2E1, EROD and GST decreased, and CYP b5 content increased significantly. In Se-deficient rats, total CYP450 level and CYP2E1 activity increased, and EROD and GST activities and CYP b5 level decreased significantly. In combined I(2) and Se deficiency, except for CYP450 content and CYP2E1 activity, all enzyme activities and CYP b5 content decreased significantly compared to control group. Overall results of this study have suggested that metabolism of xenobiotics as well as endogenous compounds is affected by Se and I(2) status.