Selenium variation induced oxidative stress regulates p53 dependent germ cell apoptosis: plausible involvement of HSP70-2

Background  Selenium at altered concentration causes abnormal spermatogenesis and male infertility. However, the exact mechanism behind this is still unexplored. Aims  It was aimed to investigate if Se induced oxidative stress alters the expressions of testis specific HSP70-2 protein, that is crucial in normal spermatogenesis. The study was extended to delineate the apoptotic process after this change if any. Methods  To create different Se status-deficient, adequate and excess, male Balb/c mice were fed yeast based Se deficient diet (group I) and this diet supplemented with Se as sodium selenite at 0.2 and 1 ppm Se (group II and III, respectively) for 8 weeks. Results  After the feeding schedule, a dose dependent change in the Se levels and GSH-Px activity was observed in samples of different Se diet fed group animals as reported in earlier studies. Changes in the redox status in both groups I and III indicated oxidative stress conditions. The mRNA and protein expression of HSP70-2 was found to be reduced in group I and III, whereas, the expressions of p53 demonstrated a reverse trend. Increased apoptosis was observed in the group I and III animals as indicated by increased apoptotic index (AI) on the TUNEL stained sections and by DNA fragmentation indicating DNA damage in these groups. Conclusion  These findings suggest that Se variations induced oxidative stress leads to germ cell apoptosis and downregulation of HSP70-2. This study suggests that there can be a possible link between these two events and the fate of HSP70-2 in case of oxidative damage can provide an insight into the mechanism(s) by which the nutritional variation induced oxidative stress can affect reproductive potential and thus demonstrates the importance of nutrition at molecular level as well.     

Metal Concentrations in the Water of Chah Nimeh Reservoirs in Zabol,Iran

The main objectives of this article were to monitor the metal concentrations of Fe, Cu, Pb, B, Ni, V, Cd, Se, As, and Cr in the water of Chah nimeh reservoirs in Zabol, south-eastern Iran; and to identify any relationships between metals. Metal concentrations in the water samples were analyzed using ICP-OES. The results indicated that there were a highly positive correlation between Cr and Se, Ni (p < 0.01), and, between As and Ni (p < 0.01). Also, there were significant differences between Cr, Ni, Pb, and Se in the water of Chah nimeh reservoirs.     

Blood-based biomarkers of selenium and thyroid status indicate possible adverse biological effects of mercury and polychlorinated biphenyls in Southern Beaufort Sea polar bears

We examined biomarkers of selenium status (whole blood Se; serum Se; glutathione peroxidase activity) and thyroid status (concentrations and ratios of thyroxine, T4; tri-iodothyronine, T3; albumin) in polar bears to assess variations among cohorts, and relationships to circulating concentrations of contaminants. Concentrations of total mercury (Hg) in whole blood were similar among cohorts (prime aged males and females, older animals, ages ≥16 years, and young animals, ages 1–5 years; 48.44±35. 81; p=0.253). Concentrations of sum of seven polychlorinated biphenyls (∑PCB₇) in whole blood were greater in females (with and without cubs, 26.44±25.82 ng/g ww) and young (26.81±10.67 ng/g ww) compared to males (8.88±5.76 ng/g ww, p<0.001), and significantly related to reduced body condition scores (p<0.001). Concentrations of Se and albumin were significantly greater in males than females (whole blood Se, males, 42.34 pmol/g ww, females, 36.25±6.27 pmol/g ww, p=0.019; albumin, males, 4.34±0.34 g/dl, females, 4.10±0.29 g/dL, p=0.018). Glutathione peroxidase activity ranged from 109.1 to 207.8 mU/mg hemoglobin, but did not differ significantly by sex or age (p>0.08). Thyroid hormones were greater in females (solitary females and females with cubs) compared to males (p<0.001). Biomarkers of Se status and concentrations of T3 were significantly positively related to Hg in all prime aged polar bears (p<0.03). Albumin concentrations were significantly positively related to total TT4, and significantly negatively related to concentrations of ∑PCB₇ (p<0.003). Total thyroxine (TT4) was significantly negatively associated with blood concentrations of ∑PCB₇ in solitary females (p=0.045). These data suggest that female polar bears were more susceptible to changes in blood-based biomarkers of selenium and thyroid status than males. Further classifications of the physiologic states of polar bears and repeated measures of individuals over time are needed to accurately assess the biological impact of combined toxicant exposures.     

Selenium-Enriched Agaricus bisporus Mushroom Protects against Increase in Gut Permeability ex vivo and Up-Regulates Glutathione Peroxidase 1 and 2 in Hyperthermally-Induced Oxidative Stress in Rats

Dietary effects of organic Se supplementation in the form of Se-enriched Agaricus bisporus mushroom on ileal mucosal permeability and antioxidant selenoenzymes status in heat induced oxidative stress in rats were evaluated. Acute heat stress (40 °C, 21% relative humidity, 90 min exposure) increased ileum baseline short circuit current (Isc; 2.40-fold) and epithelial conductance (Ge; 2.74-fold). Dietary supplementation with Se-enriched A. bisporus (1 µg Se/g feed) reduced (p < 0.05) ileum Isc and Ge during heat stress to 1.74 and 1.91 fold, respectively, indicating protection from heat stress-induced mucosal permeability increase. The expression of ileum glutathione peroxidase (GPx-) 1 and 2 mRNAs were up-regulated (p < 0.05) by 1.90 and 1.87-fold, respectively, for non-heat stress rats on the Se-enriched diet relative to the control. The interplay between heat stress and dietary Se is complex. For rats on the control diet, heat stress alone increased ileum expression of GPx-1 (2.33-fold) and GPx-2 (2.23-fold) relative to thermoneutral conditions. For rats on the Se-enriched diet, heat stress increased (p < 0.05) GPx-1 expression only. Rats on Se-enriched + α-tocopherol diet exhibited increased expression of both genes (p < 0.05). Thus, dietary Se-enriched A. bisporus protected against increase in ileum permeability and up-regulated GPx-1 and GPx-2 expression, selenoenzymes relevant to mitigating oxidative stress.     

Combined Exposure of Peripubertal Male Rats to the Endocrine-Disrupting Compound Atrazine and Power–Frequency Electromagnetic Fields Causes Degranulation of Cutaneous Mast Cells: A New Toxic Environmental Hazard?

The effects of single and combined treatments of the endocrine-disrupting compound atrazine and the power–frequency electromagnetic fields (EMFs) were investigated on cutaneous mast cells in juvenile/peripubertal male Wistar rats. Animals were divided into six groups: (1) 4 h/day exposure to EMFs (50 Hz), (2) 20 mg/kg of body weight (bw) of atrazine, (3) 200 mg/kg bw of atrazine, (4) EMFs with 20 mg/kg bw of atrazine, (5) EMFs with 200 mg/kg bw of atrazine, and (6) control. Both the atrazine and the combined treatments, but not the single EMF exposure, increased the number of degranulated mast cells. Statistically significant differences were demonstrated between the control and both of the combined treatments (p < 0.01 and p < 0.001, respectively). Additionally, low and high doses of atrazine combined with the EMFs were found significantly different when compared to the EMF group alone (both at p < 0.001). Considering the biological importance of mast cells in cutaneous immune reactions, future studies should reveal whether combined exposures to chemical and physical environmental agents pose a serious health risk.     

Leptin in the Anterior Piriform Cortex Affects Food Intake in Rats

Leptin administered intracerebroventricularly (ICV) or intrahypothalamically inhibits food intake (FI), however, to our knowledge the effects of leptin administration have only been examined in one extrahypothalamic site (dorsal raphe nucleus). Our objectives were t. (1) determine the FI effects of leptin administration into the anterior piriform cortex (APC), an area linked to the control of FI in amino acid (AA) deficiency, (2) examine leptin action during short term anorexia that develops in response to AA deficiency. Bilateral injections of leptin (0.25 μ) into the APC suppressed FI of a balanced diet between 6 and 12 h by 36% (p < 0.01) and over the first 12 and 24 h by 15% (p < 0.05). Bilateral administration of leptin (0.1 μg) inhibited FI between 12 and 24 h by approximately 48% (p < 0.05) on a threonine-imbalanced diet without significantly affecting FI on a threonine-corrected diet. The increase of plasma leptin concentrations in response to feeding a threonine-basal diet was greater than that following an AA imbalanced diet, suggesting that suppression of FI by an AA imbalanced diet is not mediated by an increase of leptin. Our results suggest that (1) administration of leptin into a brain area outside the hypothalamus suppresses FI, and (2) leptin is unlikely to play a selective role in the short term anorectic response to AA deficiency. These data are consistent with the hypothesis that endogenous leptin can act within the APC to modulate FI.     

Vitamin C and Resveratrol Supplementation to Rat Dams Treated with Di(2-ethylhexyl)phthalate: Impact on Reproductive and Oxidative Stress End Points in Male Offspring

This study was carried out to assess the influence of di(2-ethylhexyl)phthalate (DEHP) alone or associated with antioxidants on the male reproductive system in newborn rats, emphasizing the implications of oxidative stress and hormonal balance during prenatal and early postnatal periods. Wistar females were exposed by oral route to DEHP alone or associated with antioxidants from gestational day 7 to lactational day 2 according to the following treatment regimens: (C) vehicle control (canola oil + 1% Tween-80); (V) vitamin C (200 mg/kg) + canola oil; (R) resveratrol (10 mg/kg) + canola oil; (D) DEHP (500 mg/kg) + 1% Tween-80; (DV) DEHP (500 mg/kg) + vitamin C (200 mg/kg); and (DR) DEHP (500 mg/kg) + resveratrol (10 mg/kg). Two male pups per litter were randomly selected and necropsied on postnatal day 2. The brain and liver were removed and weighed and anogenital distance (AGD) was measured. Additionally, the testes were removed for assessment of intratesticular testosterone levels and histopathology; the liver was used to measure biomarkers of oxidative stress. Vitamin C and resveratrol alone did not affect the reproductive end points and did not induce oxidative stress. Exposure of dams to DEHP alone and associated with antioxidants resulted in hepatomegaly in offspring and significantly increased the incidence of multinucleated gonocytes in seminiferous cords. Testosterone and AGD presented a trend to decrease in DEHP-exposed groups. Catalase activity increased only in groups exposed to DEHP associated with antioxidants, although GST (gluthatione-S-transferase) activity decreased in all DEHP-exposed groups. The levels of hydroperoxides increased only in group exposed to DEHP associated with vitamin C. These results indicate that the association of DEHP with antioxidants was unable to ameliorate DEHP-induced reproductive changes, and the coadministration of DEHP and these antioxidants might even contribute to an overall increase in oxidative stress.     

Moderate Zinc Deficiency Increases Cell Death After Brain Injury in the Rat

Abstract

Zinc supplementation has been used clinically to reduce Zn losses and protein turnover in patients suffering from traumatic brain injury. Despite the known role of zinc in cell survival and integrity, the influence of zinc status on central nervous system wound healing in the weeks and months after brain injury has not been addressed. In this investigation, we examined cell death after unilateral cortical stab wounds in adult rats (n=5 per group) that were provided diets containing adequate zinc (30 mg Zn/kg diet), supplemental zinc (180 mg/kg), or moderately deficient zinc (5 mg/kg). Four weeks following the brain injury there was a 1.82-2.65-fold increase in terminal deoxynucleotidyl transferase-mediated biotinylated dUTP nick-end labeling (TUNEL)-positive cells with DNA fragmentation at the site of injury in animals receiving a moderately zinc deficient diet compared to animals receiving a zinc-adequate or supplemented diet (p#0.05). Examination of the nuclear morphology of these cells suggested the presence of both apoptosis and necrosis. Immunohistochemistry showed that the TUNEL-positive cells expressed both ED-1 and OX-42, identifying them as microglia/macrophages. Thus it appears that adequate zinc status may be necessary to minimize the amount of neuroimmune cell death after brain injury.     

Effects on Cholesterol Balance and LDL Cholesterol in the Rat of a Soft-Ripened Cheese Containing Vegetable Oils

Objective: The purpose of this study was to examine effects of a modified soft-ripened cheese containing vegetable oils on cholesterol status, using the rat as the experimental model and the traditional soft-ripened cheese as the control.

Methods: Adult male Wistar rats (≈370 g) were divided into two dietary groups (20 rats/group) and fed either the standard diet (STD, containing traditional cheeses made from whole milk) or the experimental diet (EXP, containing modified cheeses made from the combination of skim milk with the following fat mixture: milk fat/oleic acid-enriched sunflower oil/soybean oil mixture). Lipids of the diets came solely from cheeses (14 g/100 g diet); the EXP diet contained (3-fold) less saturated fat, (2-fold) less cholesterol, and (15-fold) more phytosterols than the STD diet.

Results: Although serum triglyceride and total cholesterol concentrations were not affected by the type of diet, the EXP diet resulted in a significant reduction of LDL-cholesterol (31%, p<0.001) and a significant increase of HDL-cholesterol (11%, p<0.05), compared to the STD diet. Thus, a marked reduction (39%) of serum LDL/HDL cholesterol ratio was observed in the EXP group (p<0.001). In addition, the two quantitative balances (excreted/ingested) of cholesterol and total neutral sterols (for which phytosterols were excluded) were significantly higher by 183% and 174%, respectively for the EXP group, compared to the STD group (p<0.05). On another hand, rats fed the EXP diet excreted more cholesterol than they ingested dietary cholesterol (cholesterol balance ? 1), indicating that those animals eliminated some endogenous cholesterol in their feces, while the opposite was true for rats fed the STD diet (cholesterol balance < 1). Finally, fecal bile salt concentration was not significantly different between the two dietary groups.

Conclusions: The partial substitution of milk fat by vegetable oils in soft-ripened cheese resulted in a decreased blood LDL/HDL cholesterol ratio and an increased fecal excretion of endogenous cholesterol and neutral sterols and, thus, markedly improved its nutritional qualities. Therefore, the consumption of the described modified cheese may meet the demand of subjects who wish to lower their risk for atherosclerosis and cardiovascular disease.     

A high-fat diet in the presence of vitamin D deficiency status is associated with a negative influence on calcaneal quantitative ultrasound parameters in young adults: a cross-sectional study

Vitamin D deficiency and a high-fat diet are considered health problems worldwide. The aims of this study were to examine the prevalence of vitamin D deficiency/insufficiency in young adults, factors related to the vitamin D status, and the influence of vitamin D deficiency and/or a high-fat diet on bone parameters. Here, we investigated the hypothesis that a high-fat diet in the presence of a vitamin D-deficient status would have a more negative influence on bone parameters than a normal-fat diet with such a status. In the present study, we targeted young Japanese adults aged 21-23 (n = 175). We conducted a diet survey based on 3-day food records, biochemical examination of serum, and quantitative ultrasound measurements at the calcaneus. As a result, the rates of vitamin D deficiency {serum 25-hydroxyvitamin D₃ [25(OH)D] concentration less than 20 ng/mL} and insufficiency [serum 25(OH)D concentration less than 30 ng/mL but not less than 20 ng/mL] were 60.6 and 30.9%, respectively. A positive correlation was observed between the serum 25(OH)D level and serum bone-specific alkaline phosphatase level, which is a serum marker of bone formation (r = 0.253, P< .01) or the speed of sound (SOS) as an index of bone density (r = 0.259, P< .01). A negative correlation was observed between the ratio of fat intake to total energy intake (%E) and serum 25(OH)D levels (r = −0.206, P< .01). Furthermore, we revealed that a high-fat diet in the presence of a vitamin D deficient status reduced the SOS parameter compared with a normal-fat diet with a vitamin D-deficient status (P< .05).     

Choice feeding of selenium-deficient laying hens affects diet selection,selenium intake and body weight

Inadequate selenium (Se) supply often in combination with low vitamin E status causes deficiency symptoms in many species. It is likely that a vague discomfort or sickness is perceived before clear deficiency signs become apparent. We investigated whether Se-deficient hens reduce their Se deficit by selecting a diet containing more selenium when offered two diets with different Se concentrations. A Low-Se diet (0.07 mg Se/kg) was supplemented with Se-enriched yeast (Sel-Plex 50) to produce Medium-Se (0.20 mg Se/kg) and High-Se (1.50 mg Se/kg) diets. Each of two consecutive study parts (I and II) with the same hens and treatments began with a 6-wk baseline period (Medium-Se diet), subsequently followed a 9-wk depletion period (Low-Se diet or Medium-Se diet), then a 6-wk choice feeding period in which two diets with different Se concentrations (Low-Se and Medium-Se, Medium-Se and High-Se, or Low-Se and High-Se) were offered. A control group received the Medium-Se diet throughout the study. Daily Se intake, calculated from daily feed intake, followed similar patterns in both parts of the study, but Se-deficient hens preferred (P < 0.05) the High-Se diet to the Low-Se diet during the first 3 wk of choice feeding only in part I. We conclude that young Se-deficient laying hens reduce their Se deficit if they have a choice between a Low-Se and a High-Se diet by preferentially selecting the High-Se diet, possibly based on learned place preference and/or learned taste aversion to the Low-Se diet, presumably in response to discomfort due to Se-deficiency.     

Dietary iron supplements and Moringa oleifera leaves influence the liver hepcidin messenger RNA expression and biochemical indices of iron status in rats

In this study, the effects of iron depletion and repletion on biochemical and molecular indices of iron status were investigated in growing male Wistar rats. We hypothesized that iron from Moringa leaves could overcome the effects of iron deficiency and modulate the expression of iron-responsive genes better than conventional iron supplements. Iron deficiency was induced by feeding rats an iron-deficient diet for 10 weeks, whereas control rats were maintained on an iron-sufficient diet (35.0-mg Fe/kg diet). After the depletion period, animals were repleted with different source of iron, in combination with ascorbic acid. Iron deficiency caused a significant (P < .05) decrease in serum iron and ferritin levels by 57% and 40%, respectively, as compared with nondepleted control animals. Significant changes in the expression (0.5- to100-fold) of liver hepcidin (HAMP), transferrin, transferrin receptor-2, hemochromatosis type 2, ferroportin 1, ceruloplasmin, and ferritin-H were recorded in iron-depleted and iron-repleted rats, as compared with nondepleted rats (P < .05). Dietary iron from Moringa leaf was found to be superior compared with ferric citrate in overcoming the effects of iron deficiency in rats. These results suggest that changes in the relative expression of liver hepcidin messenger RNA can be used as a sensitive molecular marker for iron deficiency.     

Determination of Metal (Cu,Zn, Se,Cr and Cd) Levels in Tissues of the Cyprinid Fish, <Emphasis Type="Italic">Capoeta trutta</Emphasis> (Heckel, 1843) from Different Regions of Keban Dam Lake (Euphrates-Turkey)

The aim of this study was to evaluate Copper (Cu), Zinc (Zn), Selenium (Se), Chromium (Cr) and Cadmium (Cd) concentrations in liver, muscle, gills and kidney tissues of Capoeta trutta collected from four sites of Keban Dam Lake, Turkey. The highest heavy metal level in all tissues was for Zn, while Cd was the lowest. The lowest heavy metal levels were generally found at Station 4 (Agin) for all tissues (p < 0.05). There were statistically significant differences among stations for Cu, Zn, Cr and Se in gills; for Cu, Zn, Se and Cr in liver and kidney; and Cu, Zn and Cr in muscle (p < 0.05). Cadmium concentrations did not differ between sites for any of the tissues. Turkish Food Codex sets the maximum limits of Zn, Cu and Cd as, 50, 20 and 0.05 mg kg⁻¹ dry weight, respectively, in the muscle of fish used for human consumption. In our study, the level of Zn was higher than Turkish permissible limits only at Station 3 (Guluskur). Cadmium levels were much higher than permissible limits at three stations [S1 (Pertek), S2 (Kockale) and S3], whereas Cu levels were within permissible limits in all stations.     

Selenium Deficiency during Pregnancy in Mice Impairs Exercise Performance and Metabolic Function in Adult Offspring

Selenium deficiency during the perinatal period programs metabolic dysfunction in offspring. Postnatal exercise may prevent the development of programmed metabolic disease. This study investigated the impact of selenium deficiency on offspring exercise behavior and whether this improved metabolic health. Female C57BL/6 mice were randomly allocated to control (NormalSe, >190 μg/Se/kg, n = 8) or low-selenium (LowSe, <50 μg/Se/kg, n = 8) diets from four weeks before mating. Male offspring were weaned at postnatal day (PN) twenty-four and placed on a normal chow diet. At PN60, mice were placed in cages with bi-directional running wheels and monitored until PN180. LowSe offspring had a reduced average weekly running speed and distance (p < 0.05). LowSe offspring exhibited glucose intolerance, with increased peak blood glucose (p < 0.05) and area under the curve following an intra-peritoneal injection of glucose (p < 0.05). Furthermore, mRNA expression of several selenoproteins within cardiac and skeletal muscle were increased in LowSe offspring (p < 0.05). The results indicated that selenium deficiency during development reduces exercise behavior. Furthermore, exercise does not prevent programmed glucose intolerance in low-selenium offspring. This highlights that exercise may not be the optimal intervention for metabolic disease in offspring impacted by selenium deficiency in early life.     

Total and Methyl Mercury Contents and Distribution Characteristics in Cicada, Cryptotympana atrata (Fabricius)

Total and methyl mercury concentrations of cicada bodies, wings, and exuviae were investigated to study the mercury distribution characteristics. Results indicated that total and methyl mercury concentrations of cicada bodies were 2.64 mg/kg and 123.93 ng/g on average, respectively. In cicada tissues, total mercury concentrations were found to increase in the order of exuviae (0.50 mg/kg on average) < wings (0.98 mg/kg on average) < cicada bodies (2.64 mg/kg on average) and methyl mercury concentrations of cicada bodies were 123.93 ng/g on average and were the highest. Methyl mercury concentrations accounted for about 4.69% of total mercury in cicada bodies and most mercury was in inorganic forms in cicada. Sex differences of total mercury concentrations were significantly great (F = 8.433, p < 0.01) and total mercury concentrations of the males, which were 3.38 mg/kg on average, were much higher. Correlation analysis showed that neither total nor methyl mercury concentrations of cicada bodies was significantly related to the corresponding contents of soil (r = 0.0598, p > 0.05).     

Impact of the Mediterranean diet with and without weight loss on plasma cell adhesion molecule concentrations in men with the metabolic syndrome

No study has yet examined how weight loss specifically modifies the impact of the Mediterranean diet (MedDiet) on plasma cell adhesion molecules (CAM) in men with the metabolic syndrome (MetS). Therefore, this study examined the impact of the MedDiet consumed under controlled feeding conditions, with and without weight loss, on plasma CAM concentrations in men with the MetS. The diet of 26 men (age 24–62 years) with the MetS was first standardized to a North American control diet for 5 weeks followed by a 5-week MedDiet, both under weight-maintaining isocaloric feeding conditions. Participants then underwent a 20-week caloric restriction period that led to a 10.2 ± 2.9% reduction in body weight (p < 0.01), followed by the consumption of an isocaloric weight stable MedDiet for 5 weeks. All foods including red wine were provided during the isocaloric phases of the study. There was no change in the average concentrations of any of the CAM after the MedDiet without weight loss. The MedDiet combined with weight loss reduced plasma CAM concentrations by 10.9% (p < 0.01) compared with the control diet and by 6.8% (p = 0.068) compared with the MedDiet without weight loss. These data suggest that weight loss is required for the MedDiet to improve plasma CAM concentrations over a short period of time in men with the MetS. ClinicalTrial.gov registration number: NCT00988650.     

Clinical evidence of efficacy of red yeast rice and berberine in a large controlled study versus diet

Efficacy of a new patented proprietary combination of natural nutraceuticals (PN) containing natural hypolipidemic as red yeast, policosanol and berberine was tested in a large study on dyslipidemic patients in clinical practice. A parallel, controlled, randomized, multicenter study was designed. After 2 weeks on a stable dietary regimen, the patients were randomized to PN 1 tablet/day associated with diet (PN + D) or diet alone (D) for 16 weeks. Entry criteria were: Tot-Chol >200 mg/dL or LDL-Chol >150 mg/dL without a clear indication for statins, or plasma triglycerides >150 mg/dL. Lipid pattern and CV parameters were evaluated at baseline and monthly. 1,751 patients were enrolled in 248 Italian units, 933 patients on PN + D and 818 on D. The baseline lipid values were: Tot-Chol 255.4 versus 243.1 mg/dL, LDL-Chol 170.1 versus 162.2 mg/dL, HDL-Chol 50.0 versus 48.8 mg/dL, and TG 190.5 versus 184.4 mg/dL. PN constantly and significantly improved lipid parameters versus D group: at 16 weeks −19.1 versus −9.4% for Tot-Chol (p < 0.001), −23.5 versus −10.8% for LDL-Chol (p < 0.001), +11.6 versus +4.0% for HDL-Chol (p < 0.001), −17.9 versus −11.3% for TG (p < 0.001). In conclusions, PN plus diet allows an effective improvement of blood lipids with a significant reduction of global CV risk, suggesting a role for PN in CHD prevention.     

Interaction between cadmium (Cd), selenium (Se) and oxidative stress biomarkers in healthy mothers and its impact on birth anthropometric measures

To our knowledge, this study may be the first to examine the antagonistic role of selenium (Se) on oxidative stress induced by cadmium (Cd) and its impact on birth measures. Cd and Se levels were measured in umbilical-cord blood and the placentas of a subsample of 250 healthy mothers who participated between 2005 and 2006 in the project “Prenatal Exposure to Pollutants”. The median Cd levels in cord and maternal blood and placental tissue were 0.78 μg/l, 0.976 μg/l and 0.037 μg/g dry wt., respectively. The median levels of Se in cord serum and placental tissue were 65.68 μg/l and 1.052 μg/g dry wt., respectively. Se was more than 100-fold in molar excess over Cd in both cord serum and placental tissue. The median molar Cd/Se ratios in cord serum and placental tissue were 0.008 and 0.024, respectively, which were much lower than unity. This study suggests that both Cd and Se play a role in the mechanism of oxidative stress, but, the process underlying this mechanism remains unclear. Nevertheless, three biomarkers of oxidative stress had inconsistent relationships with Cd and/or Se in various matrices, perhaps due to potential untested confounders. Our results generally support an association between low in utero exposure to Cd and the anthropometric development of the fetus. Adjusted regression models indicated a negative association of cord blood Cd levels ≥0.78 μg/l with Apgar 5-min scores and birth height. Maternal Cd levels ≥0.976 μg/l were associated with a 5.94-fold increased risk of small-for-gestational-age births, which increased to 7.48-fold after excluding preterm births. Placenta weight decreased with increasing placental Cd levels ≥0.037 μg/g dry wt. (p = 0.045), an association that became stronger after excluding preterm births or adjusting for birth weight. Cord Se levels ≥65.68 μg/l were positively associated with placenta weight (p = 0.041) and thickness (p = 0.031), an association that remained unchanged after excluding preterm births. Cord Se levels, however, were negatively associated with cephalization index, but only after excluding preterm births (p = 0.017). Each birth measure was again modeled as a function of the Cd/Se ratios in cord blood and placenta tissue. Interestingly cord ratios ≥0.008 were negatively associated with Apgar-5 min score (p = 0.047), birth weight (p = 0.034) and placenta thickness (p = 0.022). After excluding preterm births, only the association with placenta thickness remained significant (p = 0.021), while birth weight (p = 0.053) was marginally significant. In contrast, cephalization index increased with Cd/Se ratios ≥0.008 (p = 0.033), an association that became marginally significant after excluding preterm births (p = 0.058). For placental Cd/Se ratios ≥0.024, only placenta weight was reduced with (p = 0.037) and without (p = 0.009) the inclusion of preterm births. These findings do not support an antagonistic mechanism between Cd and Se. The role of oxidative mechanisms either induced by Cd exposure or alleviated by Se on these birth anthropometric measures was examined by principal component analysis. Se did not have a clear protective role against Cd-induced adverse effects despite its substantial excess over Cd, and its role in alleviating oxidative stress by reducing malondialdehyde levels. The results may suggest that the extent of the Se beneficial effects is not governed only by its concentration but also by the chemical forms of Se that interact with various proteins. Consequently, the speciation of Se in such studies is essential for understanding and predicting Se availability for absorption.     

The effects of whey protein and chromium picolinate supplementation on visceral fat and metabolic status in high-fat-fed rats

The objective of this study was to evaluate the effects of whey protein (WP) and chromium picolinate (CrPic) on body composition and metabolic status in rats fed a high-fat diet (HFD). Male Wistar rats (n = 10/group, 8 weeks old) were divided into three groups. The control group was fed a HFD (300 g fat/kg diet). The other two groups were fed the HFD plus 320 g whey protein isolate/kg diet (HFD + WP) with or without 80 mcg CrPic/kg body wt/day (HFD + WP + CrPic). After six weeks, rats were fasted, blood samples were drawn, and visceral and subcutaneous fat pads were removed and weighed. Daily food intake was not affected by treatment. Rats fed HFD exhibited significant increases in body weight, body fat and metabolic risk factors (p ≤ 0.05). Rats fed the HFD + WP showed a significant decrease in body weight, serum glucose and blood lipids, and a significant increase in insulin levels (p ≤ 0.05). Rats fed the HFD + WP + CrPic had the lowest levels in total visceral fat, triglycerides, total cholesterol and free fatty acids, and the highest insulin levels (p ≤ 0.05). Tissue concentrations of chromium (Cr) increased with CrPic supplementation (p < 0.001). The results of this study support the use of WP and CrPic supplementation to improve body composition and metabolic syndrome risk factors.     

Metallothionein Gene Expression in Liver of Rats Exposed to Cadmium and Supplemented with Zinc and Selenium

Cadmium (Cd), one of the most widely distributed heavy metals, is highly toxic to humans and animals. It is well known that zinc (Zn) and selenium (Se) administration reduce the Cd-induced toxicity and that metallothioneins can have a protective effect to mitigate Cd toxicity in biological systems. In this study we report the expression analysis of the two metallothioneines gene classes MT-1 and MT-2 as well as the total metalloprotein content in the liver of rats exposed to Cd (200 ppm), Cd + Zn (200 ppm + 500 ppm), Cd + Se (200 ppm + 0.1 ppm) or Cd + Zn + Se (200 ppm + 500 ppm + 0.1 ppm) in their drinking water for 35 days. Metals accumulation was quantified in rat liver. Cd decreased significantly the hepatic concentrations of Se and increased those of Zn. The treatment of Cd-exposed rats with Se alone or combined with Zn reversed the Cd-induced depletion of Se concentrations in the liver. However, Zn or Zn + Se administration significantly increased the liver Cd uptake and had no effect on the Cd-induced increase in hepatic concentrations of Zn. The molecular assay showed a decreasing trend of MT-1 relative gene expression levels in animals supplemented with Zn (6.87-fold), Se (3.58-fold), and their combination (1.69-fold) when compared to Cd-treated animals (16.22-fold). Upregulation of the MT-2 expression were recorded in all conditions, although fold induction levels were less pronounced than MT-1 expressions. Our data suggest that the well-established protective effect of Zn and Se against Cd-induced toxicity passes through non-MT gene expression mechanisms, being more dependent on the oxidative stress status of the cell.