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 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.

The effects of di(2-ethylhexyl)phthalate exposure and selenium nutrition on sertoli cell vimentin structure and germ-cell apoptosis in rat testis.

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 <0.0033). DEHP exposure caused disruption and collapse of vimentin filaments and significantly induced apoptotic death of germ cells (approximately 8-fold, p <0.0033). In DEHP-exposed Se-deficient animals, compared with the control, collapse of vimentin filaments was more prominent; there was serious damage to the seminiferous epithelium; and a high increment (approximately 25-fold, p <0.0033) in apoptotic germ cells was observed. Thus, Se deficiency exacerbated the toxicity of DEHP on Sertoli cells and spermatogenesis, whereas Se supplementation provided protection. These results put forward the critical role of Se in the modulation of redox status of testicular cells and emphasize the importance of Se status for reproductive health.

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.

Reproductive toxicity of di(2-ethylhexyl) phthalate in selenium-supplemented and selenium-deficient rats.

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.

Evaluation of cytotoxicity and oxidative DNA damaging effects of di(2-ethylhexyl)-phthalate (DEHP) and mono(2-ethylhexyl)-phthalate (MEHP) on MA-10 Leydig cells and protection by selenium.

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 µM 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.

Ciprofloxacin-induces free radical production in rat cerebral microsomes.

In the presence of ciprofloxacin (CPFX), free radical adduct formation was demonstrated in rat cerebral microsomes using a spin trap α-(4-pyridyl-1-oxide)-N-tert-butyl-nitrone by electron spin resonance spectroscopy. Active microsomes, dihydronicotinamide-adenine dinucleotide phosphate, and ciprofloxacin were necessary for the formation of a spin trap/radical adduct. Adduct formation increased dose-dependently at 0.5-1 mM CPFX concentration for 180 min, and 0.3-1 mM concentration level for 240 min. The addition of SKF 525A, ZnCl2 or desferrioxamine to the incubation system caused complete inhibition of the radical formation. However, pretreatment of microsomal system with superoxide dismutase (SOD) did not induce any protective effect. Induction of lipid peroxidation, and depletion of thiol levels by CPFX were also shown in the system. These results strongly suggested that CPFX produces free radical(s) in the cerebral microsomes of rats.

Cytotoxic effect of ciprofloxacin in primary culture of rat astrocytes and protection by Vitamin E.

The aim of this study was to investigate the possible cytotoxic and oxidative stress inducing effects of ciprofloxacin (CPFX) on primary cultures of rat astrocytes. The cultured cells were incubated with various concentrations of CPFX (0.5-300mg/l), and cytotoxicity was determined by neutral red (NR) and MTT assays. Survival profile of cells was biphasic in NR assay: CPFX did not cause any alteration at any concentration for 7h, whereas < or =50mg/l concentrations induced significant cell proliferation in incubation periods of 24, 48, 72, and 96h. However, cell proliferation gradually decreased at higher concentrations, and 200 and 300mg/l of CPFX exposure was found to be significantly (p<0.05) cytotoxic at all time periods. With MTT assay, no alteration was noted for incubation period of 7h, as observed with NR assay. But, cell viability decreased with approximately > or =50mg/l CPFX exposure in all other time periods. Cell proliferation was only seen in 24h of incubation with 0.5 and 5mg/l CPFX. Vitamin E pretreatment of cell cultures were found to be providing complete protection against cytotoxicity of 300mg/l CPFX in 96h incubation when measured with both NR and MTT assays. The SOD pretreatment was partially protective with NR assay, but no protection was noted when measured with MTT. A significant enhancement of lipid peroxidation was observed with the cytotoxic concentration of the drug, but total glutathione content and catalase activity of cells did not change. The data obtained in this study suggest that, in accordance with our previous results with fibroblast cells, CPFX-induced cytotoxicity is related to oxidative stress. And the biphasic effect of CPFX possibly resulted from the complex dose-dependent relationships between reactive oxygen species, cell proliferation, and cell viability.

Trace elements in growth: iodine and selenium status of Turkish children.

Starting from the fetal life and increasing the need throughout the childhood, adequate intake of micronutrients is of great importance for the proper development of structure and function of the body, and the well being. However, micronutrient deficiency is widespread in many populations of the world mainly due to nutritional insufficiencies and/or inadequate and unbalanced nutrition. While iodine and selenium (Se) are inadequately available for men and live stock in many parts of the world, Turkey is one of those countries where iodine deficiency (ID) is widespread, Se levels are marginal. In this communication, importance of adequate iodine and Se nutrition and status of Turkish children is summarized.

Ciprofloxacin-induced DNA damage in primary culture of rat astrocytes and protection by Vitamin E.

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

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.

Ciprofloxacin-Induced Cytotoxicity and Apoptosis in HeLa Cells.

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

The 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.

Oxidative DNA base damage, antioxidant enzyme activities and selenium status in highly iodine-deficient goitrous children.

The objective of this study was to investigate oxidative DNA damage, and the levels of antioxidant enzymes (AOE) and selenium (Se) in relation to iodine deficiency and/or goiter in children. The study was performed in a group of goitrous high school children (15-18 years of age) (n = 14) with severe or moderate iodine deficiency. Thyroid hormones (TSH, FT4, TT4, FT3, TT3), urinary iodine (UI) and plasma Se levels, and erythrocyte glutathione peroxidase (GSHPx), superoxide dismutase (SOD) and catalase (CAT) activities were determined and compared with those of a control group consisting of non-goitrous high school children (n = 14) with normal UI levels or mild iodine deficiency. In the goitrous group, concentrations of FT4, TT4, plasma Se and UI, and activities of GSHPx and SOD were found to be significantly lower. Six typical hydroxyl radical-induced base lesions in genomic DNA of peripheral blood were identified and quantified by gas chromatography/isotope-dilution mass spectrometry (GC/IDMS), and higher levels of DNA base lesions were observed in the goitrous group. The results suggest that highly iodine-deficient goitrous children may be under oxidative stress, which may lead to greater level of oxidative damage to DNA. This study supports the evidence for the reported relationship between iodine deficiency and the increased incidence of thyroid malignancies.

The effect of vitamin E supplementation on antioxidant enzyme activities and lipid peroxidation levels in hemodialysis patients.

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.

Iodine and/or selenium deficiency alters tissue distribution pattern of other trace elements in rats.

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.

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.

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.

Low doses of selenium specifically stimulate the repair of oxidative DNA damage in LNCaP prostate cancer cells.

Epidemiological studies have demonstrated an inverse relationship between selenium (Se) intake and cancer incidence and/or mortality. However, the molecular mechanisms underlying the cancer chemopreventive activity of Se compounds remain largely unknown. The objective of this study was to investigate the effect of low doses of Se on the stimulation of DNA repair systems in response to four different qualities of DNA damage. P53-proficient LNCaP human prostate adenocarcinoma cells were grown either untreated or in the presence of low concentrations of two Se compounds (30° nM sodium selenite, or 10 µM selenomethionine) and exposed to UVA, H2O2, methylmethane sulfonate (MMS) or UVC. Cell viability as well as DNA damage induction and repair were evaluated by the alkaline Comet assay. Overall, Se was shown to be a very potent protector against cell toxicity and genotoxicity induced by oxidative stress (UVA or H2O2) but not from the agents that induce other types of deleterious lesions (MMS or UVC). Furthermore, Se-treated cells exhibited increased oxidative DNA repair activity, indicating a novel mechanism of Se action. Therefore, the benefits of Se could be explained by a combination of antioxidant activity, the reduction in DNA damage and the enhancement of oxidative DNA repair capacity.