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.

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.

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.

Cod liver oil supplementation improves cardiovascular and metabolic abnormalities in streptozotocin diabetic rats.

Abnormalities in the metabolism of essential fatty acids and the results of increased oxidative stress have been implicated in cardiovascular disorders observed in diabetes mellitus. This study, therefore, aimed to investigate the effects of cod liver oil (CLO, Lysi Ltd, Iceland), which comprises mainly an antioxidant vitamin A, n:3 polyunsaturated fatty acids (n:3 PUFAs), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), on cardiovascular abnormalities in streptozotocin (STZ)-diabetic rats. Two days after single STZ (55 mg kg(-1), i.p.) or vehicle injection, diabetes was verified by increased blood glucose, and non-diabetic and diabetic rats were left untreated or treated with CLO (0.5 mL kg(-1) daily, by intragastric probing) for 12 weeks. Plasma glucose, triacylglycerol and cholesterol concentrations were significantly elevated in 12-week untreated-diabetic rats; CLO provided better weight gain, entirely prevented the plasma lipid abnormalities, but partially controlled the glycaemia in diabetic rats. In isolated aorta rings, diabetes resulted in increased phenylephrine-induced vasoconstriction and isoprenaline-induced vasorelaxation, impaired endothelium-dependent vasodilatation and unchanged responsiveness to sodium nitroprusside. CLO treatment completely prevented endothelial deficiency, partly corrected the phenylephrine-induced vasoconstriction and did not affect the responses to isoprenaline and sodium nitroprusside in diabetic aorta. Diabetes also produced a marked decrease in the rate of spontaneously beating right atria and a significant increase in basal contractile force of left ventricular papillary muscle. The responsiveness of right atria to the positive chronotropic effect of isoprenaline was significantly decreased in diabetic rats, and was increased in CLO-treated diabetic rats. The positive chronotropic effect of noradrenaline was markedly increased in diabetic atria, but prevented by CLO treatment. Diabetes also resulted in an increased positive inotropic response of papillary muscle to both noradrenaline and isoprenaline, which were prevented by CLO treatment. CLO treatment also resulted in lower tissue sensitivity (pD(2)) to these agonists in diabetic papillary muscle. Ventricular hydroxyproline content was found to be unchanged among the experimental groups. The ultrastructure of diabetic myocardium displayed various degenerations (i.e. intracellular oedema, myofibrillar fragmentation, condensed pleomorphic mitochondria, thick capillary irregular basement membrane, swollen endothelial cells), which were partially prevented by CLO treatment. We conclude that the supplementation with CLO is effective in preventing cardiovascular disorders observed in experimental diabetes.

Effect of PUVA, narrow-band UVB and cyclosporin on inflammatory cells of the psoriatic plaque.

BACKGROUND: Because antigen presenting is necessary for T-cell activation, antigen-presenting cells should be involved in the pathogenesis of psoriasis. In this study, our purpose was to evaluate and compare effects of PUVA, cyclosporine A and narrow-band UVB on dendritic cells and activated lymphocytes in the psoriatic lesions. METHODS: Forty-five volunteered patients (15 patients in each treatment group as PUVA, cyclosporin A and narrow-band UVB) were enrolled in this study. Lesional skin biopsies were taken from each patient before and after treatments. Fresh frozen biopsies were studied for the expressions of CD1a, CD68, CD86, CD4, CD8 and HLA-DR proteins by immunohistochemistry. RESULTS: There was no correlation between severity of the lesions and expressions of the antigens. Only PUVA significantly decreased CD1a+ epidermal Langerhans cells' (LCs) counts. Treatment modalities decreased expression of costimulator CD86, and most of them decrease antigen-presenting capacity of skin by decreasing HLA class-II expression. CONCLUSIONS: All treatment modalities equally reduce lymphocytes, macrophages and dendritic cells. PUVA is the only treatment that decreases epidermal LCs. All treatments effectively diminish expression of CD86 and inhibit this step of inflammation.