Inhibition of membrane Na(+)-K+ Atpase of the brain, liver and RBC in rats administered di(2-ethyl hexyl) phthalate (DEHP) a plasticizer used in polyvinyl chloride (PVC) blood storage bags

Significant amounts of di(2-ethylhexyl) phthalate (DEHP) leach out into blood stored in DEHP plasticized polyvinyl chloride (PVC) bags resulting in the exposure of recipients of blood transfusion to this compound. The aim of this study was to find out whether DEHP at these low levels has any effect on the activity of membrane Na(+)-K+ ATPase, since a decrease in this enzyme activity has been reported to take place in a number of disorders like neurodegenerative and psychiatric disorders, coronary artery disease and stroke, syndrome-X, tumours etc. DEHP was administered (ip) at a low dose of 750 microg/100 g body weight to rats and the activity of membrane Na(+)-K+ ATPase in liver, brain and RBC was estimated. Histopathology of brain, activity of HMG CoA reductase (a major rate limiting enzyme in the isoprenoid pathway of which digoxin, the physiological inhibitor of Na(+)-K+ ATPase is a product), intracellular concentration of Ca2+ and Mg2+ in RBC (which is altered as a result of inhibition of Na(+)-K+ ATPase) were also studied. (In the light of the observation of increase of intracellular Ca2+ load and intracellular depletion of Mg2+ when Na(+)-K+ ATPase is inhibited). Histopathology of brain revealed areas of degeneration in the rats administered DEHP. There was significant inhibition of membrane Na(+)-K+ ATPase in brain, liver and RBC. Intracellular Ca2+ increased in the RBC while intracellular Mg2+ decreased. However activity of hepatic HMG CoA reductase decreased. Activity of Na(+)-K+ ATPase and HMG CoA reductase, however returned to normal levels within 7 days of stopping administration of DEHP. The inhibition of membrane Na(+)-K+ ATPase activity by DEHP may indicate the possibility of predisposing recipients of transfusion of blood or hemodialysis to the various disorders mentioned above. However since this effect is reversed when DEHP administration is stopped, it may not be a serious problem in the case of a few transfusion; but in patients receiving repeated blood transfusion as in thalassemia patients or patients undergoing hemodialysis, possibility of this risk has to be considered. This inhibition is a direct effect of DEHP or its metabolites, since activity of HMG CoA reductase, (an enzyme which catalyses a major rate limiting step in the isoprenoid pathway by which digoxin, the physiological inhibitor of Na(+)-K+ ATPase is synthesized) showed a decrease.     

Comparison of the effects of di(2-ethylhexyl)phthalate, a peroxisome proliferator, on the vitamin metabolism involved in the energy formation in rats fed with a casein or gluten diet

In order to find an alleviation method for the adverse effect of environmental endocrine disrupters, we studied the effects of the putative endocrine disrupter and peroxisome proliferator, di(2-ethylhexyl)phthalate (DEHP), on animal growth and vitamin metabolism. It is known that the effects of chemical compounds such as xenobiotics differ according to the dietary protein source. We compared the effects of dietary DEHP administration on rats fed with a diet containing milk casein or wheat gluten. The increased conversion ratio of tryptophan to nicotinamide by DEHP administration was significantly higher in the casein group than in the gluten group. We also investigated the effects of DEHP on the urinary excretion of other vitamins. DEHP administration resulted in decreased urinary excretion of vitamin B(1), vitamin B(2), and pantothenic acid.     

Iron status and oxidative stress in beta-thalassemia patients in Jakarta

A study on thalassemia intermedia and major patients in Jakarta was initiated to obtain a comprehensive picture of metabolic dysregulation, iron overload, oxidative stress, and cell damage. Data are presented from a group of 14 transfusion-dependent patients in an age range of 11-25 years (T) and another group of 9 frequently transfused (for at least 15 years) patients aged 17-30 years (L). A third group comprised 6 patients (aged 7 to 14 years) who had not yet obtained transfusions (N). The 21 controls (C) were voluntary students without diagnosis or clinical signs of thalassemia up to 30 years of age. The study was approved by the Ethical Clearance Board of the Medical Faculty and all blood samples from controls and patients were obtained on fully informed consent. Levels of antioxidants (vitamins A, C, E and beta-carotene) and reactive thiols are considerably decreased in transfused patients, whereas signs of iron overload and cell damage are increased (serum iron, ferritin, transferrin saturation, SGOT, SGPT, gamma-GT, bilirubin). Results can be summarized that non-transfused thalassemia intermedia patients exert slight signs of oxidative stress, and increased hemoglobin degradation but no significant indication of tissue or cell damage. This picture differs considerably from transfusion-dependent thalassemia major patients: highly significant decrease in antioxidants and thiols and tremendous iron overload and cell damage. The picture is even worsened in long-term transfused patients. Iron chelation after transfusion is not sufficient in Indonesia, because it is normally (with few exceptions) applied only once together with transfusion. Hence, one major reason of the bad condition of transfusion-dependent thalassemia patients in Indonesia appears to be frequent transfusions (on the average one per month) and insufficient chelation of one treatment per month together with transfusion.     

Association between Maternal Exposure to di(2-ethylhexyl) Phthalate and Reproductive Hormone Levels in Fetal Blood: The Hokkaido Study on Environment and Children's Health

Prenatal di(2-ethylhexyl) phthalate (DEHP) exposure can produce reproductive toxicity in animal models. Only limited data exist from human studies on maternal DEHP exposure and its effects on infants. We aimed to examine the associations between DEHP exposure in utero and reproductive hormone levels in cord blood. Between 2002 and 2005, 514 pregnant women agreed to participate in the Hokkaido Study Sapporo Cohort. Maternal blood samples were taken from 23–35 weeks of gestation and the concentration of the primary metabolite of DEHP, mono(2-ethylhexyl) phthalate (MEHP), was measured. Concentrations of infant reproductive hormones including estradiol (E2), total testosterone (T), and progesterone (P4), inhibin B, insulin-like factor 3 (INSL3), steroid hormone binding globulin, follicle-stimulating hormone, and luteinizing hormone were measured from cord blood. Two hundred and two samples with both MEHP and hormones'' data were included in statistical analysis. The participants completed a self-administered questionnaire regarding information on maternal characteristics. Gestational age, birth weight and infant sex were obtained from birth records. In an adjusted linear regression analysis fit to all study participants, maternal MEHP levels were found to be associated with reduced levels of T/E2, P4, and inhibin B. For the stratified analyses for sex, inverse associations between maternal MEHP levels T/E2, P4, inhibin B, and INSL3 were statistically significant for males only. In addition, the MEHP quartile model showed a significant p-value trend for P4, inhibin B, and INSL3 decrease in males. Since inhibin B and INSL3 are major secretory products of Sertoli and Leydig cell, respectively, the results of this study suggest that DEHP exposure in utero may have adverse effects on both Sertoli and Leydig cell development in males, which agrees with the results obtained from animal studies. Comprehensive studies investigating phthalates'' exposure in humans, as well as their long-term effects on reproductive development are needed.     

Protective influence of vitamin E on antioxidant defense system in the blood of rats treated with cadmium

The effects of acute exposure to cadmium (Cd) on the blood antioxidant defense system, lipid peroxide concentration and hematological parameters, as well as the possible protective role of vitamin E were studied. Male Wistar albino rats (3 months old) were treated with cadmium (0.4 mg Cd/kg b.m., i.p., 24 h before the experiment) or with vitamin E + Cd (20 IU Vit E/kg b.m., i.m., 48 h + 0.4 mg Cd/kg b.m., i.p., 24 h before the experiment). The hematological parameters were assessed: red blood cell counts, hematocrit value and hemoglobin concentration were significantly decreased in the blood of Cd-treated rats. Intoxication with cadmium was also followed by significantly increased lipid peroxide concentrations. We also observed increased activity of antioxidant defense enzymes: copper zinc containing superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase and glutathione-S-transferase as well as concentrations of non-enzymatic components of antioxidant defense system: reduced glutathione, vitamin C and vitamin E. Pretreatment with vitamin E exhibited a protective role on the toxic effects of cadmium on the hematological values, lipid peroxide concentration as well as on enzymatic and non-enzymatic components of antioxidant defense system.     

Immune status of Greek patients with beta-thalassemia major negative for anti-HIV

Patients with thalassemia who receive multiple blood transfusions are at risk for the acquired immunodeficiency syndrome. Peripheral blood lymphocyte subpopulations were studied in 22 multitransfused thalassemic patients; 10 patients were without splenectomy and 12 were studied after splenectomy. Both groups were negative for anti-HIV. Four additional patients who were found positive for anti-HIV and ten healthy controls were also included in this study. Patients without splenectomy compared to controls and to patients after splenectomy showed a significant decrease of both percentage (p less than 0.001) and absolute numbers (p less than 0.001) of Leu-7+ cells without significant abnormalities of T4/T8 ratio (1.56 +/- 0.4). Patients after splenectomy compared to controls and to patients without splenectomy showed a significant increase of the absolute numbers of lymphocytes and lymphocytes subsets T11+, T3+, T4+, T8+ and SmIg+ cells. In the seropositive patients for HIV only a significant increase of the absolute number of T8+ cells was observed while the T4/T8 ratio was 1.24 +/- 0.73. The decrease in the percentage of Leu-7+ cells in patients without splenectomy correlated inversely to the total amount of blood transfused. In conclusion patients with thalassemia had normal T4/T8 ratio and did not show the abnormal immunologic profile that has been reported in haemophiliacs.     

Diethyl Hexyl Phthalate (DEHP) is associated with insulin resistance in adipose tissue of male rat: Protective role of antioxidant vitamins (C & E)

Diethyl hexyl phthalate (DEHP) is a plasticizer, commonly used in a variety of products, including lubricants, perfumes, hairsprays and cosmetics, construction materials, wood finishers, adhesives, floorings and paints. DEHP is an endocrine disruptor and it has a continuum of influence on various organ systems in human beings and experimental animals. However, specific effects of DEHP on insulin signaling in adipose tissue are not known. Adult male albino rats of Wistar strain were divided into four groups. Control, DEHP treated (dissolved in olive oil at a dose of 10, and 100 mg/kg body weight, respectively, once daily through gastric intubations for 30 days) and DEHP + vitamin E (50 mg/kg body weight) and C (100 mg/kg body weight) dissolved in olive oil and distilled water, respectively, once daily through gastric intubations for 30 days. After the completion of treatment, adipose tissue was dissected out to assess various parameters. DEHP treatment escalated H₂O₂ and hydroxyl radical levels as well as lipid peroxidation in the adipose tissue. DEHP impaired the expression of insulin signaling molecules and their phosphorelay pathways leading to diminish plasma membrane GLUT4 level and thus decreased glucose uptake and oxidation. Blood glucose level was elevated as a result of these changes. Supplementation of vitamins (C & E) prevented the DEHP‐induced changes. It is concluded that DEHP‐induced ROS and lipid peroxidation disrupts the insulin signal transduction in adipose tissue and favors glucose intolerance. Antioxidant vitamins have a protective role against the adverse effect of DEHP. J. Cell. Biochem. 114: 558–569, 2013. © 2012 Wiley Periodicals, Inc.     

Evaluation of vitamin E requirement and food palatability in rabbits fed a purified diet with a high fish oil content

The vitamin E requirement of rabbits fed a semi-synthetic diet containing high amounts of fish oil was studied. Three groups of 5 rabbits were fed fish oil diets containing, respectively, 50, 100 and 500 mg/kg vitamin E. Moreover diet palatability was evaluated by using different levels of grass meal: 0.5, 1 and 2%, respectively. Incorporation of 1% grass meal in the diet was sufficient to achieve acceptance of the fish oil diet. Increased vitamin E intake resulted in a dose-related rise in vitamin E levels in serum, blood platelets, liver and adipose tissue. The higher vitamin E intake was reflected by a twofold increase of vitamin E in serum, platelets and adipose tissue, and a tenfold increase in the liver. The adipose tissue revealed histopathological changes of yellow fat disease, mainly in the low-dose vitamin E group. In the liver microgranulomas of lipofuscin-laden macrophages were seen. Vitamin E was found to decrease but not to prevent the formation of these lesions. The results indicate that protection of marine oils against in vivo oxidation is problematic in the rabbit. It is questionable whether in this animal vitamin E is an adequate biological anti-oxidant for very long chain n-3 fatty acids.     

Distribution of Tocotrienols in Rats Fed a Rice Bran Tocotrienol Concentrate

To examine the distribution of rice bran tocotrienol (T3), we gave rice bran T3 to rats after considering an acceptable daily intake of vitamin E for humans. Male SD rats (5 weeks of age) were fed for 3 weeks on a commercial diet containing 6.4 mg of vitamin E per 100 g wt and additively received vitamin E or the vehicle (vitamin E-free corn oil) by oral intubation. The animals were randomly divided into 4 groups depending on the type of test diet: control (vehicle), non-T3 (no T3 + 4.3 mg of tocopherol (TOC)/kg body weight (b.w.)/day), low-T3 (0.8 mg T3 + 3.5 mg TOC/kg b.w./day), and high-T3 (3.2 mg T3 + 1.1 mg TOC/kg b.w./day). The control rats and rats in the non-T3, low-T3, and high-T3 groups took 4.3 and 8.6 mg of vitamin E/kg b.w./day, respectively. Rice bran γ-T3 was significantly distributed to the adipose tissue and increased from 1.1 to 10.2 nmol/g of adipose tissue according to the rice bran T3 intake.     

Supplementation with vitamin E but not with vitamin C lowers lipid peroxidation in vivo in mildly hypercholesterolemic men.

Although the use of vitamin E supplements has been associated with a reduction in coronary events, assumed to be due to lowered lipid peroxidation, there are no previous long-term clinical trials into the effects of vitamin C or E supplementation on lipid peroxidation in vivo. Here, we have studied the long-term effects of vitamins C and E on plasma F2-isoprostanes, a widely used marker of lipid peroxidation in vivo. As a study cohort, a subset of the "Antioxidant Supplementation in Atherosclerosis Prevention" (ASAP) study was used. ASAP is a double-masked placebo-controlled randomized clinical trial to study the long-term effect of vitamin C (500 mg of slow release ascorbate daily), vitamin E (200 mg of D-alpha-tocopheryl acetate daily), both vitamins (CellaVie), or placebo on lipid peroxidation, atherosclerotic progression, blood pressure and myocardial infarction (n = 520 at baseline). Lipid peroxidation measurements were carried out in 100 consecutive men at entry and repeated at 12 months. The plasma F2-isoprostane concentration was lowered by 17.3% (95% CI 3.9-30.8%) in the vitamin E group (p = 0.006 for the change, as compared with the placebo group). On the contrary, vitamin C had no significant effect on plasma F2-isoprostanes as compared with the placebo group. There was also no interaction in the effect between these vitamins. In conclusion, long-term oral supplementation of clinically healthy, but hypercholesterolemic men, who have normal vitamin C and E levels with a reasonable dose of vitamin E lowers lipid peroxidation in vivo, but a relatively high dose of vitamin C does not. This observation may provide a mechanism for the observed ability of vitamin E supplements to prevent atherosclerosis.     

Distribution of tocotrienols in rats fed a rice bran tocotrienol concentrate

To examine the distribution of rice bran tocotrienol (T3), we gave rice bran T3 to rats after considering an acceptable daily intake of vitamin E for humans. Male SD rats (5 weeks of age) were fed for 3 weeks on a commercial diet containing 6.4 mg of vitamin E per 100 g wt and additively received vitamin E or the vehicle (vitamin E-free corn oil) by oral intubation. The animals were randomly divided into 4 groups depending on the type of test diet: control (vehicle), non-T3 (no T3 + 4.3 mg of tocopherol (TOC)/kg body weight (b.w.)/day), low-T3 (0.8 mg T3 + 3.5 mg TOC/kg b.w./day), and high-T3 (3.2 mg T3 + 1.1 mg TOC/kg b.w./day). The control rats and rats in the non-T3, low-T3, and high-T3 groups took 4.3 and 8.6 mg of vitamin E/kg b.w./day, respectively. Rice bran gamma-T3 was significantly distributed to the adipose tissue and increased from 1.1 to 10.2 nmol/g of adipose tissue according to the rice bran T3 intake.     

Correlation of hepcidin and serum ferritin levels in thalassemia patients at Chiang Mai University Hospital

Hepcidin is a key iron-regulatory hormone, the production of which is controlled by iron stores, inflammation, hypoxia and erythropoiesis. The regulation of iron by hepcidin is of clinical importance in thalassemia patients in which anemia occurs along with iron overload. The present study aimed to evaluate the correlation between serum hepcidin and ferritin levels in thalassemia patients. This cross-sectional study investigated 64 patients with thalassemia; 16 β-thalassemia major (BTM), 31 β-thalassemia/hemoglobin (Hb) E (BE), and 17 Hb H + AE Bart’s disease (Hb H + AE Bart’s). The levels of serum hepcidin and ferritin, and Hb of the three groups were measured. The median values of serum ferritin and Hb were significantly different among the three groups, whereas serum hepcidin values were not observed to be significantly different. The correlation of the serum hepcidin and ferritin levels was not statistically significant in any of the three groups of thalassemia patients with BTM, BE, or Hb H + AE Bart’s (r = −0.141, 0.065 and −0.016, respectively). In conclusion, no statistically significant correlations were observed between serum hepcidin with any variables including serum ferritin, Hb, age, labile plasma iron (LPI), and number of blood transfusion units among the three groups of thalassemia patients. Likely, the regulation of hepcidin in thalassemia patients is affected more by erythropoietic activity than iron storage.     

Intermittent fasting ameliorates di-(2-ethylhexyl) phthalate-induced precocious puberty in female rats: A study of the hypothalamic–pituitary–gonadal axis

Di-(2-ethylhexyl) phthalate has been reported to interfere with the development and function of animal reproductive systems. However, hardly any studies provide methods to minimize or prevent the adverse effects of DEHP on reproduction. The energy balance state of mammals is closely related to reproductive activities, and the reproductive axis can regulate reproductive activities according to changes in the body's energy balance state. In this study, the effects of every other day fasting (EODF), as a way of intermittent fasting, on preventing the precocious puberty induced by DEHP in female rats was studied. EODF significantly improved the advancement of vaginal opening age (as the markers of puberty onset) and elevated serum levels of luteinizing hormone and estradiol (detected by ELISA) induced by 5 mg kg^?1 DEHP exposure (D5). The mRNA and western blot results showed that the EODF could minimized the increase of gonadotropin-releasing hormone expression induced by DEHP exposure. The administration of DEHP could elevate the levels of kisspeptin protein and the number of kisspeptin-immunoreactive neurons in anteroventral periventricular nucleu, and this increase was diminished considerably by EODF treatment. In contrast, the D5 and D0 groups showed no remarkable difference in the level of Kiss1 expression in arcuate nucleus, whereas the D5 + EODF group had a remarkable decrease in kisspeptin expression as compared with the other two groups. Our results indicated that EODF might inhibit the acceleration of puberty onset induced by DEHP exposure via HPG axis.     

Protective effects of vitamin E and curcumin on L-thyroxine-induced rat testicular oxidative stress

Present study examines effects of curcumin and vitamin E on oxidative stress parameters, antioxidant defence enzymes and oxidized (GSSG) and reduced glutathione (GSH) levels in testis of L-thyroxine (T4)-induced hyperthyroid rats. The oxidative stress in T4-treated rat testis was evident from elevation in oxidative stress parameters such as lipid peroxide and protein carbonyl contents, decrease in superoxide dismutase (SOD) and catalase (CAT) activities and increase in glutathione peroxidase (GPx) activity. This is accompanied with decrease in number and mortality of epididymal sperms. When the T4-treated rats were fed with vitamin E and/or curcumin, the lipid peroxide and protein carbonyl contents in crude homogenates of testes decreased to normal level. Treatment of curcumin and/or vitamin E to T4-treated rats resulted in elevation of SOD level in postmitochondrial fraction (PMF) and mitochondrial fraction (MF) and CAT in PMF, with decreased GPx activity in MF. However, curcumin or vitamin E was unable to change GPx activity alone but in together they elevated the GPx in PMF of T4-treated rat testis. Both the antioxidants are incapable of producing significant changes in GSH:GSSG ratio of PMF of T4-treated rats. In MF, GSH:GSSG ratio elevated and decreased respectively by curcumin and vitamin E treatments to T4-treated rats, however, in together these antioxidants caused an elevated GSH:GSSG ratio with a value less than when vitamin E given alone to T4-treated rats. Vitamin E not the curcumin elevates total sperm count and percentage of live sperm impaired by hyperthyroid state. In summary, both vitamin E and curcumin are efficient in protecting testis from oxidative stress generated by T4 mainly in restoring antioxidant enzymes to the level of euthyroid animals up to some extent but vitamin E is more efficient than curcumin.     

Treatment of Tumors with Vitamin E Suppresses Myeloid Derived Suppressor Cells and Enhances CD8+ T Cell-Mediated Antitumor Effects

Vitamin E has been shown to have strong anticarcinogenic properties, including antioxidant characteristics, making it an ideal candidate for use in combination with immunotherapies that modify the tumor microenvironment. The tumor microenvironment contains immunosuppressive components, which can be diminished, and immunogenic components, which can be augmented by immunotherapies in order to generate a productive immune response. In the current study, we employ the α-tocopherol succinate isomer of vitamin E to reduce immunosuppression by myeloid derived suppressor cells (MDSCs) as well as adoptive transfer of antigen-specific CD8+ T cells to generate potent antitumor effects against the HPV16 E7-expressing TC-1 tumor model. We show that vitamin E alone induces necrosis of TC-1 cells and elicits antitumor effects in TC-1 tumor-bearing mice. We further demonstrate that vitamin E reverses the suppression of T cell activation by MDSCs and that this effect is mediated in part by a nitric oxide-dependent mechanism. Additionally, treatment with vitamin E reduces the percentage of MDSCs in tumor loci, and induces a higher percentage of T cells, following T cell adoptive transfer. Finally, we demonstrate that treatment with vitamin E followed by E7-specific T cell adoptive transfer experience elicits potent antitumor effects in tumor-bearing mice. Our data provide additional evidence that vitamin E has anticancer properties and that it has promise for use as an adjuvant in combination with a variety of cancer therapies.     

Supplementation with vitamin E but not with vitamin C lowers lipid peroxidation in vivo in mildly hypercholesterolemic men

Although the use of vitamin E supplements has been associated with a reduction in coronary events, assumed to be due to lowered lipid peroxidation, there are no previous long-term clinical trials into the effects of vitamin C or E supplementation on lipid peroxidation in vivo. Here, we have studied the long-term effects of vitamins C and E on plasma F₂-isoprostanes, a widely used marker of lipid peroxidation in vivo. As a study cohort, a subset of the “Antioxidant Supplementation in Atherosclerosis Prevention” (ASAP) study was used. ASAP is a double-masked placebo-controlled randomized clinical trial to study the long-term effect of vitamin C (500 mg of slow release ascorbate daily), vitamin E (200 mg of d-α-tocopheryl acetate daily), both vitamins (CellaVie^®), or placebo on lipid peroxidation, atherosclerotic progression, blood pressure and myocardial infarction (n = 520 at baseline). Lipid peroxidation measurements were carried out in 100 consecutive men at entry and repeated at 12 months. The plasma F₂-isoprostane concentration was lowered by 17.3% (95% CI 3.9–30.8%) in the vitamin E group (p = 0.006 for the change, as compared with the placebo group). On the contrary, vitamin C had no significant effect on plasma F₂-isoprostanes as compared with the placebo group. There was also no interaction in the effect between these vitamins. In conclusion, long-term oral supplementation of clinically healthy, but hypercholesterolemic men, who have normal vitamin C and E levels with a reasonable dose of vitamin E lowers lipid peroxidation in vivo, but a relatively high dose of vitamin C does not. This observation may provide a mechanism for the observed ability of vitamin E supplements to prevent atherosclerosis.     

Dimethoate Induces Kidney Dysfunction, Disrupts Membrane-Bound ATPases and Confers Cytotoxicity Through DNA Damage. Protective Effects of Vitamin E and Selenium

Dimethoate (DM) is an organophosphate insecticide widely used in agriculture and industry and has toxic effects on non-target organisms especially mammalian. However, we still know little about DM-induced kidney injury and its alleviation by natural antioxidants. In the present study, selenium (Se), vitamin E, DM, Se+DM, vitamin E+DM, Se+vitamin E+DM were given to adult rats for 4 weeks. Plasma creatinine and uric acid, kidney MDA, PC, H₂O₂ and AOPP levels were higher, while Na⁺-K⁺-ATPase and LDH values were lower in the DM group than those of controls. A smear without ladder formation on agarose gel was shown in the DM group, indicating random DNA degradation and DM-induced genotoxicity. A decrease in kidney GSH, NPSH and plasma urea levels and an increase in GPx, SOD and catalase activities were observed in the DM group when compared to those of controls. Plasma cystatin C levels increased, indicating a decrease in glomerular filtration rate. When Se or vitamin E was added through diet, the biochemical parameters cited above were partially restored in Se+DM and vitamin E+DM than DM group. The joint effect of Se and vitamin E was more powerful against DM-induced oxidative stress and kidney dysfunction. The changes in biochemical parameters were substantiated by histological data. In conclusion, our results indicated a possible mechanism of DM-induced nephrotoxicity, where renal genotoxicity was noted, membrane-bound ATPases and plasma biomarkers were disturbed. Se and vitamin E ameliorated the toxic effects of this pesticide in renal tissue suggesting their role as potential antioxidants.     

Effect of vitamin E on sperm number and testis histopathology of sodium arsenite-treated rats

The aims of this study were to investigate the adverse effects of sodium arsenite on the reproductive system of male rats as well as to examine whether vitamin E is able to ameliorate these effects. Adult rats were divided into four groups: 1/ control, 2/ sodium arsenite (8 mg/kg/day), 3/ vitamin E (100 mg/kg/day), and 4/ sodium arsenite +vitamin E group. Treatments were administered orally by gavage for eight weeks. After treatment, body and left testis weights were recorded and the testis was used for the histological analysis. Left cauda epididymis was used to count sperm number. Body and testis weight did not differ among the groups (p>0.05). A significant decrease (p<0.001) in sperm number and mean diameter of seminiferous tubules as well as a significant increase (p<0.001) in the mean diameter of seminiferous tubules' lumen were found in sodium arsenite group compared to those of controls. Sodium arsenite did not affect the morphology and diameter of spermatogonial nucleus (p>0.05). In the sodium arsenite + vitamin E group, vitamin E ameliorated (p<0.001) the adverse effects of sodium arsenite on sperm number as well as the diameters of tubule and lumen. In addition, the treatment of rats with vitamin E alone significantly (p<0.001) increased the diameter of seminiferous tubules and significantly (p<0.001) decreased seminiferous tubules' lumen compared to the control group. Vitamin E appeared to ameliorate the adverse effects of sodium arsenite on epididymal sperm number and some morphometrical parameters of the adult rat testis.     

Effects of intraperitoneally injected selenium and vitamin E in rats anesthetized with halothane.

Halothane, commonly used for anesthetizing humans and animals, is one of the most important volatile anesthetics and may cause the formation of free radicals during its biotransformation. Free radicals may lead to degeneration of liver cells. Vitamin E and glutathione peroxidase (GSH-Px) containing selenium are two natural antioxidants, and these may protect the cellular lipid and lipoproteins against oxidative damage caused by free radicals. Therefore, the purposes of the present study were to investigate the probable protective effects of intraperitoneally administered Se and vitamin E on liver enzymes and to determine some other hematological parameters in the halothane anesthesia of rats. All rats were randomly divided into five groups. The first group was used as a control, and physiological saline (0.9%) was intraperitoneally injected into these animals as a placebo. The second group was used as an anesthesia control group and was only anesthetized with halothane for two hours. The third group received intraperitoneally administered Se (Na2SeO3, 0.3 mg/200 g body weight), the fourth group vitamin E (dl-alpha-tocopheryl acetate, 100 mg/kg body weight), and the fifth group a Se plus vitamin E combination (Na2SeO3, 0.3 mg/200 g body weight + dl-alpha-tocopheryl acetate, 100 mg/kg body weight). The activities of aspartate aminotransferase, alanine aminotransferase and alkaline phosphatase, triglycerides, erythrocyte counts, the packet-cell volume, hemoglobin concentrations and neutrophyle rates significantly increased (p < 0.05 to p < 0.01) after halothane anesthesia and returned to near control levels after Se, vitamin E and Se plus vitamin E injections. The values of cholesterol, total protein, white blood cell counts and lymphocyte rates significantly decreased (p < 0.05 to p < 0.01) in the anesthesia control group. However, the levels of albumin, total bilirubin, creatinine, the mean corpuscular volume, the mean corpuscular hemoglobin, and the mean corpuscular hemoglobin concentration were not statistically influenced. In conclusion, we have determined that halothane anesthesia affected some liver enzymes and some other biochemical and hematological parameters. Se, vitamin E and their combination may prevent the increase of liver enzymes after halothane anesthesia. Based upon these results, Se and vitamin E may play an important role in the indication of hepatic cellular injury produced by halothane.     

Effects of vitamin D supplementation and circuit training on indices of obesity and insulin resistance in T2D and vitamin D deficient elderly women

[Purpose]

The purpose of this study was to investigate the effects of vitamin D supplementation and circuit training on body composition, abdominal fat, blood lipids, and insulin resistance in T2D and vitamin D deficient elderly women.

[Methods]

Fifty-two elderly women were randomly assigned to either the vitamin D supplementation with circuit training group (D+T: n = 15), the circuit training group (T: n = 13), the vitamin D supplementation group (D: n = 11), or the control group (CON: n = 13). The subjects in D took vitamin D supplements at 1,200 IU per day for 12 weeks; the subjects in T exercised 3 to 4 times per week, 25 to 40 minutes per session for 12 weeks; and the subjects in D+T participated in both treatments. Subjects in CON were asked to maintain normal daily life pattern for the duration of the study. Body composition, abdominal fat, blood lipids, and surrogate indices for insulin resistance were measured at pre- and post-test and the data were compared among the four groups and between two tests by utilizing two-way ANOVA with repeated measures. The main results of the present study were as follows:

[Results]

1) Body weight, fat mass, percent body fat, and BMI decreased significantly in T, whereas there were no significant changes in the variables in D and CON. Lean body mass showed no significant changes in all groups. 2) TFA and SFA decreased significantly in T, whereas there were no significant changes in the variables in D and CON. The other abdominal fat related variables showed no significant changes in all groups. 3) TC, TG, HDL-C, and LDL-C showed improvements in T, whereas there were no significant changes in the variables in D and CON. 4) Fasting glucose, fasting insulin, and HOMA-IR tended to be lower in D+T.

[Conclusion]

It was concluded that the 12 weeks of vitamin D supplementation and circuit training would have positive effects on abdominal fat and blood lipid profiles in T2D and vitamin D deficient elderly women. Vitamin D supplementation was especially effective when it was complemented with exercise training.