Association between prenatal nickel exposure and preterm low birth weight: possible effect of selenium.

There is a proposed link between prenatal nickel (Ni) exposure and preterm low birth weight (PLBW); however, this association remains unclear. Selenium (Se) may modify this relationship by protecting against Ni toxicity. Concentrations of Ni and Se were measured in urine samples collected from 408 pregnant women (102 PLBW cases and 306 matched controls) in China. Conditional logistic regression was utilized to explore the association between Ni levels and PLBW, as well as the effect modification by Se on this association. A significant association was observed between higher maternal urinary Ni levels and risk of PLBW [adjusted odds ratio (OR) = 2.80 (95% confidence interval (CI): 1.44, 5.44) for the highest tertile], and this association was more apparent among female infants than that among male infants. Further analyses showed that mothers with high urinary Ni and low urinary Se levels had a significantly increased risk for PLBW [adjusted OR = 2.87 (95% CI: 1.09, 7.56)] compared with the mothers with low urinary Ni and high urinary Se levels. Our study indicates that prenatal exposure to Ni was a risk factor for PLBW. Se might provide protection against the toxicity of Ni.

Insights into the toxicity of iron oxides nanoparticles in land snails.

The use of manufactured nanoparticles (NPs) is spreading rapidly across technology and medicine fields, posing concerns about their consequence on ecosystems and human health. The present study aims to assess the biological responses triggered by iron oxide NPs (IONPs) and iron oxide NPs incorporated into zeolite (IONPZ) in relation to oxidative stress on the land snail Helix aspersa in order to investigate its use as a biomarker for terrestrial environments. Morphology and structure of both NPs were characterized. Snail food was supplemented with a range of concentrations of IONPs and IONPZ and values of the hemocyte lysosomal membranes' destabilization by 50% were estimated by the neutral red retention (NRRT50) assay. Subsequently, snails were fed with NPs concentrations equal to half of the NRRT50 values, 0.05 mg L-1 for IONPs and 1 mg L-1 for IONPZ, for 1, 5, 10 and 20 days. Both effectors induced oxidative stress in snails' hemocytes compared to untreated animals. The latter was detected by NRRT changes, reactive oxygen species (ROS) production, lipid peroxidation estimation, DNA integrity loss, measurement of protein carbonyl content by an enzyme-linked immunoabsorbent assay (ELISA), determination of ubiquitin conjugates and cleaved caspases conjugates levels. The results showed that the simultaneous use of the parameters tested could constitute possible reliable biomarkers for the evaluation of NPs toxicity. However, more research is required in order to enlighten the disposal and toxic impact of iron oxide NPs on the environment to ensure their safe use in the future.

Potential Role of L-Arginine and Vitamin E Against Bone Loss Induced by Nano-Zinc Oxide in Rats.

The purpose of this study was to illustrate the effects of zinc oxide nanoparticles (ZnO-NPs) administration on bone turnover and bone resorbing agents in rats and how L-arginine (L-arg) or vitamin E (vit E) co-administrations might affect them. Fasting rats were randomly divided into four groups (n = 10): G1-normal healthy animals; G2-ZnO-NPs-exposed rats (600 mg/kg-1/day-1); G3-ZnO-NPs-exposed rats co-administrated L-arg (200 mg/kg-1/day-1); G4-ZnO-NPs-exposed rats co-administrated vit E (200 mg/kg-1/day-1). The ingredients were orally administered daily. The body weight and food consumption of rats were recorded during the administration period and the experiment continued for three consecutive weeks. The results demonstrated that ZnO-NPs administration induced bone loss in rats as manifested by reduced activity of bone alkaline phosphatase (B-ALP) and increased level of C-terminal peptide type I collagen (CTx). The increase of inflammatory markers, tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) by ZnO-NPs suggests that deleterious effects of ZnO-NPs on bone turnover were, in part, due to inflammation. Confirming to this suggestion, both L-arg and vit E reduced TNF-α and IL-6 levels and consequently decreased bone resorption as indicated by reduced serum CTx level. This study proved that ZnO-NPs can induce bone turnover, which may be reduced by L-arg or vit.E co-administration, partly by anti-inflammatory mechanism.

Silver nanoparticle exposure in pregnant rats increases gene expression of tyrosine hydroxylase and monoamine oxidase in offspring brain.

CONTEXT: Maternal exposure to silver nanoparticles (AgNPs) affects neurobehavioral reflexes and spatial memory formation in offspring. Although the transmission of AgNPs into the brain has been reported, its toxic effect on dopamine metabolism in the brain of offspring has not been studied so far. OBJECTIVE: The aim of the present study was to investigate the expression levels of tyrosine hydroxylase (TH) and monoamine oxidase A (MAO-A) genes in the brain of offspring exposed in utero to various concentrations of AgNPs. MATERIALS AND METHODS: Time mated pregnant adult rats were assigned into three groups including control, low dose of AgNPs (0.2 mg/kg) and high dose of AgNPs (2 mg/kg). AgNPs were subcutaneously (SC) injected at days of 1, 4, 7, 10, 13, 16 and 19 of pregnancy. Gene expression of TH and MAO-A was analyzed in the brain of offspring (male and female) at days of 1, 7, 14 and 21 after birth. RESULTS: Administration of AgNPs to pregnant rats in a time- and dose-dependent manner increased the expression levels of TH in the brain of male and female pups at all tested days after birth (p < 0.05). AgNPs had stimulatory effect on MAO-A mRNA expression in pups only at the age of 7 and 14. Female pups showed the higher level of TH and MAO-A compared to that in male pups (p < 0.001). DISCUSSION AND CONCLUSIONS: Results obtained here demonstrated that the exposure of pregnant rats to AgNPs increases the expression of genes involved in dopamine metabolism in the brain of offspring.

Resveratrol ameliorates benzo(a)pyrene-induced testicular dysfunction and apoptosis: involvement of p38 MAPK/ATF2/iNOS signaling.

Benzo(a)pyrene [B(a)P] is an environmental toxicant that alters the steroidogenic profile of testis and induces testicular dysfunction. In the present study, we have investigated the molecular signaling of B(a)P and the ameliorative potential of the natural aryl hydrocarbon receptor (AhR) antagonist and antioxidant, resveratrol, on B(a)P-induced male reproductive toxicity. Studies showed that B(a)P treatment resulted in p38 MAPK activation and increased inducible nitric oxide synthase (iNOS) production along with testicular apoptosis and steroidogenic dysfunction. Resveratrol cotreatment maintained testicular redox potential, increased serum testosterone level and enhanced expression of major testicular steroidogenic proteins (CYPIIA1, StAR, 3ßHSD, 17ßHSD) and prevented subsequent onset of apoptosis. Resveratrol cotreatment resulted inhibition of testicular cytochrome P4501A1 (CYP1A1) expression, which is the major B(a)P metabolizing agent for BPDE-DNA adduct formation. Resveratrol also significantly decreased the B(a)P-induced AhR protein level, its nuclear translocation and subsequent promoter activation, thereby decreased the expression of CYP1A1. Resveratrol also down-regulated B(a)P-induced testicular iNOS production through suppressing the activation of p38 MAPK and ATF2, thus improved the oxidative status of the testis and prevented apoptosis. Our findings cumulatively suggest that resveratrol inhibits conversion of B(a)P into BPDE by modulating the transcriptional regulation of CYP1A1 and acting as an antioxidant thus prevents B(a)P-induced oxidative stress and testicular apoptosis.

Anorexic action of deoxynivalenol in hypothalamus and intestine.

Although deoxynivalenol (DON) suppresses food intake and subsequent weight gain, its contribution to anorexia mechanisms has not been fully clarified. Thus, we investigated the anorexic actions of DON in the hypothalamus and intestine, both organs related to appetite. When female B6C3F1 mice were orally exposed to different doses of DON, a drastic anorexic action was observed at a dose of 12.5 mg/kg body weight (bw) from 0 to 3 h after administration. Exposure to DON (12.5 mg/kg bw) for 3 h significantly increased the hypothalamic mRNA levels of anorexic pro-opiomelanocortin (POMC) and its downstream targets, including melanocortin 4 receptor, brain-derived neurotrophic factor, and tyrosine kinase receptor B; at the same time, orexigenic hormones were not affected. In addition, exposure to DON significantly elevated the hypothalamic mRNA levels of proinflammatory cytokines (IL-1ß, TNF-α, and IL-6) and activated nuclear factor-kappa B (NF-κB), an upstream factor of POMC. These results suggest that DON-induced proinflammatory cytokines increased the POMC level via NF-κB activation. Moreover, exposure to DON significantly enhanced the gastrointestinal mRNA levels of anorexic cholecystokinin (CCK) and transient receptor potential ankyrin-1 channel (TRPA1), a possible target of DON; these findings suggest that DON induced anorexic action by increasing CCK production via TRPA1. Taken together, these results suggest that DON induces anorexic POMC, perhaps via NF-κB activation, by increasing proinflammatory cytokines in the hypothalamus and brings about CCK production, possibly through increasing intestinal TRPA1 expression, leading to anorexic actions.

Influence of α-tocopherol and α-lipoic acid on bisphenol-A-induced oxidative damage in liver and ovarian tissue of rats.

Bisphenol A (BPA) is a commonly used material in daily life, and it is argued to cause oxidative stress in liver and ovarian tissue. α-Lipoic acid (ALA) and α-tocopherol (ATF), two of the most effective antioxidants, may play a role in preventing the toxic effect. Therefore, the purpose of this study was to examine the beneficial effects of ALA, ATF, and that of ALA + ATF combination on oxidative damage induced by BPA. Female Wistar rats were divided into five groups (control, BPA, BPA + ALA, BPA + ATF, and BPA + ALA + ATF). BPA (25 mg/kg/day), ALA (100 mg/kg/day), and ATF (20 mg/kg/day) were administered for 30 days. The levels of serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT), liver malondialdehyde (L-MDA) and glutathione peroxidase (L-GPx), and ovarian malondialdehyde (Ov-MDA) and nitric oxide (Ov-NO) were significantly higher in the BPA-treated groups compared with the control group. The levels of AST and ALT decreased in the BPA + ALA, BPA + ATF, and BPA + ALA + ATF groups compared with the BPA group. Similarly, BPA + ALA or BPA + ATF led to decreases in L-MDA and Ov-MDA levels compared with the BPA group. However, the BPA + ALA + ATF group showed a significant decrease in L-MDA levels compared with the BPA + ALA group and the BPA + ATF group. The levels of L-GPx decreased in the BPA + ATF and the BPA + ALA + ATF groups compared with the BPA group. The administration of ATF and ALA + ATF significantly decreased the Ov-NO levels. This study demonstrates that BPA causes oxidative damage in liver and ovarian tissues. ALA, ATF, or their combination were found to be beneficial in preventing BPA-induced oxidative stress.

Di-(2-ethylhexyl) phthalate adjuvantly induces imbalanced humoral immunity in ovalbumin-sensitized BALB/c mice ascribing to T follicular helper cells hyperfunction.

Di-(2-ethylhexyl) phthalate (DEHP) has been considered as a widespread environmental persistent organic pollutant and its potential concern on human health is raised by previous studies. In particular, children are more likely to be exposed to DEHP through gastrointestinal route and consequently are more susceptible to DEHP hazards. Some reports have uncovered a positive association between DEHP exposure and an increased prevalence of allergic diseases in infants and juveniles. Allergy is a hypersensitive reaction rooted in imbalanced humoral immunity. T follicular helper cell (Tfh), an important CD4(+) Th cell subset, until recently has been identified as a key player in humoral immune response by modifying B cells functions. Tfh cells are therefore perceived as the therapeutic target of immune disorders. In the present study, focusing on the newly confirmed Tfh cells, we examined the effects of DEHP on humoral immunity and investigated the underlying mechanisms. Using ovalbumin (OVA) sensitization weanling mice model under the condition of gastrointestinal exposure to DEHP, we found that DEHP acted as an immunoadjuvant to augment OVA-specific IgE and IgG1 production, amplified germinal center formation in lymphoid nodule, as well as stimulated the expansion of CD4(+)CXCR5(+)ICOS(+)/CD4(+)CXCR5(+)PD-1(+) Tfh cells and CD19(+)CD138(+)GL7(+) plasma cells. Based on the results of immune adoptive transfusion, DEHP-related anaphylactic response was ascribed to Tfh cells hyperfunction directly. We further proved that DEHP gavage together with OVA sensitization adjuvantly promoted the synthesis of cytokines IL-21 and IL-4 and the expression of transcription factors Bcl-6 and c-Maf in Tfh cells. In conclusion, our study demonstrates that DEHP has adjuvant toxic effects on Tfh cells by synthesizing an excess of cytokines IL-21 and IL-4 via over-expression of transcription factors Bcl-6 and c-Maf, leading to an increasing secretion of allergy-related IgE and IgG1.

Influence of oily vehicles on fetal testis and lipid profile of rats exposed to di-butyl phthalate.

It has been hypothesized that oils containing high levels of omega-3 polyunsaturated fatty acids, such as canola and fish oil, could counteract some of the adverse effects induced by phthalates. In the present study, the influence of different oily vehicles on di-butyl phthalate (DBP)-induced testicular toxicity and lipid profile was investigated. Pregnant Wistar rats were treated by oral gavage from gestation days 13 to 20 with DBP (500 mg/kg/day) diluted in three different vehicles: corn, canola or fish oil. Male fetuses were analyzed on gestation day 20. DBP exposure lowered intratesticular testosterone levels and anogenital distance, regardless of the vehicle used. The percentage of seminiferous cords containing multinucleated gonocytes and cord diameter was increased in DBP-exposed groups, compared with vehicle controls, with no difference between the three DBP-exposed groups. Clustering of Leydig cells was seen in all DBP groups. Lipid profile indicated that administration of canola and fish oil can increase the content of omega-3 fatty acids in rat testis. However, content of omega-3 was diminished in DBP-treated groups. Overall, our results indicate that different oily vehicles did not alter fetal rat testicular toxicity induced by a high DBP dose.

Disruption of reproductive aging in female and male rats by gestational exposure to estrogenic endocrine disruptors.

Polychlorinated biphenyls (PCBs) are industrial contaminants and known endocrine-disrupting chemicals. Previous work has shown that gestational exposure to PCBs cause changes in reproductive neuroendocrine processes. Here we extended work farther down the life spectrum and tested the hypothesis that early life exposure to Aroclor 1221 (A1221), a mixture of primarily estrogenic PCBs, results in sexually dimorphic aging-associated alterations to reproductive parameters in rats, and gene expression changes in hypothalamic nuclei that regulate reproductive function. Pregnant Sprague Dawley rats were injected on gestational days 16 and 18 with vehicle (dimethylsulfoxide), A1221 (1 mg/kg), or estradiol benzoate (50 µg/kg). Developmental parameters, estrous cyclicity (females), and timing of reproductive senescence were monitored in the offspring through 9 months of age. Expression of 48 genes was measured in 3 hypothalamic nuclei: the anteroventral periventricular nucleus (AVPV), arcuate nucleus (ARC), and median eminence (females only) by real-time RT-PCR. Serum LH, testosterone, and estradiol were assayed in the same animals. In males, A1221 had no effects; however, prenatal estradiol benzoate increased serum estradiol, gene expression in the AVPV (1 gene), and ARC (2 genes) compared with controls. In females, estrous cycles were longer in the A1221-exposed females throughout the life cycle. Gene expression was not affected in the AVPV, but significant changes were caused by A1221 in the ARC and median eminence as a function of cycling status. Bionetwork analysis demonstrated fundamental differences in physiology and gene expression between cycling and acyclic females independent of treatment. Thus, gestational exposure to biologically relevant levels of estrogenic endocrine-disrupting chemicals has sexually dimorphic effects, with an altered transition to reproductive aging in female rats but relatively little effect in males.

The toxic effects of nickel chloride on liver, erythropoiesis, and development in Wistar albino preimplanted rats can be reversed with selenium pretreatment.

The exposure to nickel chloride (NiCl2) can cause hematotoxicity and hepatotoxicity and canaffect development. The present study pertains to the protective effect of selenium (Se) against NiCl2-induced toxicity in preimplanted Wistar albino rats. The subcutaneous (s.c.) administration of 25 or 50 mg/kg of NiCl2 to Wistar albino rats on day 3 of gestation induced an immediate and significant decrease in maternal body weight and anemia 2 days after treatment. In addition, an increase in plasma aspartate aminotransferase (AST) was observed. These effects were maintained on day 20 of gestation. Moreover, a significant increase in plasma alanine aminotransferase (ALT) levels was observed with the administration of 25 mg/kg of NiCl2. Conversely, administration of 50 mg/kg of NiCl2 by s.c. injection increased erythropoiesis at day 20 of gestation and decreased platelets counts. In addition, administration of 100 mg/kg of NiCl2 markedly reduced the maternal body weight and number of live fetuses and increased fetal loss, predominantly at the end of the experimental period. All dose levels of NiCl2 caused an alteration in the hepatic histoarchitecture. When 0.3-mg/kg Se was injected s.c. with 100-mg/kg NiCl2, the levels of plasma AST and ALT and the structure of the liver were restored. Administration of 20 mg/L/day of NiCl2 in the drinking water significantly reduced the maternal body weight at day five of gestation as well as erythropoiesis during the exposure period. The present study suggests that Se can counteract the nocuous effect of nickel on the liver; however this antioxidant did not prevent alterations in development and erythropoiesis.

Cobalt-induced changes in the spleen of mice from different stages of development.

Cobalt(II) accumulates in organs such as spleen, kidneys, heart, and liver. The aim of the present study was to investigate the effects of cobalt ethylenediamine tetraacetic acid (Co-EDTA) on spleen of developing mice. Pregnant BALB/c mice in late gestation were subjected to Co-EDTA treatment at daily doses of 75 or 125 mg/kg in drinking water, which continued until d 90 of the newborn pups. The newborn pups were sacrificed on d 18, 25, 30, 45, 60, and 90, which correspond to different stages of development. Spleens were excised, weighed, and processed for histological analysis. Spleen index (SI) was calculated as a ratio of spleen weight to body weight. Cobalt(II) bioaccumulation in spleen was determined using flame atomic absorption spectrometry (FAAS). Preliminary results showed that chronic treatment of mice with low- or high-dose Co-EDTA disturbed extramedullary hematopoiesis in the spleen. The number of megakaryocytes was reduced compared to controls. SI was also reduced in d 18 mice treated with low- or high-dose Co-EDTA. However, exposure to 75 mg/kg led to an increase of SI in all other experimental groups. FAAS analysis revealed significant cobalt(II) accumulation in spleen of treated mice. The Co(II) levels in spleens of d 18 mice were highest compared to other experimental groups, indicating that at this period mice are more sensitive to treatment. Exposure to cobalt-EDTA resulted in accumulation of Co(II) in spleen, altered SI, and hematopoiesis. Immature mice appear to be more sensitive to chronic treatment than adults.

The profile of ß-amyloid precursor protein expression of rats induced by aluminum.

The environmental agent aluminum has been extensively investigated for a potential relationship with amyloid precursor protein (APP) expression. Despite many investigations, there is at present no definite proof from which to draw a conclusion. Since APP is an integral membrane protein expressed in different tissues and capable of fluxes across the blood-brain barrier (BBB), which may ultimately affect APP level in brain, it is necessary to assess the expression profile among vital body organs. The present study compared aluminum oxide and aluminum chloride injected rats with control rats (saline treated) to observe if aluminum affected APP expression patterns in different organs by immunohistochemistry (IHC). The expression of APP was observed in the brain of aluminum chloride treated rats and in the liver of aluminum oxide injected group. Results of double IHC staining showed that it is Kupffer cells, which are located in liver sinus and expressed APP after aluminum oxide treatment. Oxidative stress is suggested as the potential pathway that aluminum chloride exert effects in brain. These results suggest that different aluminum compounds may impact the expression of APP in brain and liver tissues. The mechanism that aluminum induced liver APP expression still needs further investigation.

Perinatal exposure to environmental contaminants detected in Canadian Arctic human populations changes bone geometry and biomechanical properties in rat offspring.

Arctic inhabitants consume large proportions of fish and marine mammals, and are therefore continuously exposed to levels of environmental toxicants, which may produce adverse health effects. Fetuses and newborns are the most vulnerable groups. The aim of this study was to evaluate changes in bone geometry, mineral density, and biomechanical properties during development following perinatal exposure to a mixture of environmental contaminants corresponding to maternal blood levels in Canadian Arctic human populations. Sprague-Dawley rat dams were dosed with a Northern Contaminant Mixture (NCM) from gestational day 1 to postnatal day (PND) 23. NCM contains 27 contaminants comprising polychlorinated biphenyls, organochlorine pesticides, and methylmercury. Femurs were collected on PND 35, 77 and 350, and diaphysis was analyzed by peripheral quantitative computed tomography and three-point bending test, while femoral neck was assessed in an axial loading experiment. Dose-response modeling was performed to establish the benchmark dose (BMD) for the analyzed bone parameters. Exposure to the high dose of NMC resulted in short and thin femur with reduced mechanical strength in offspring at PND35. BMD of femur length, cortical area, and stiffness were 3.2, 1.6, and 0.8 mg/kg bw/d, respectively. At PND77 femur was still thin, but at PND350 no treatment-related bone differences were detected. This study provides new insights on environmental contaminants present in the maternal blood of Canadian Arctic populations, showing that perinatal exposure induces bone alterations in the young offspring. These findings could be significant from a health risk assessment point of view.

Alumina nanoparticles enhance growth of Lemna minor.

The industrial use of nanoparticles is rapidly increasing, and this has given rise to concerns about potential biological impacts of engineered particles released into the environment. So far, relatively little is known about uptake, accumulation and responses to engineered nanoparticles by plants. In this study, the effects of alumina nanoparticles on growth, morphology and photosynthesis of Lemna minor were quantified. It was found that alumina nanoparticles substantially increase biomass accumulation of L. minor. Such a stimulatory effect of alumina nanoparticles on growth has not been reported previously. Enhanced biomass accumulation was paralleled by morphological adjustments such as increased root length and number of fronds per colony, and by increased photosynthetic efficiency. Metal nanoparticles have previously been shown to enhance the energy transfer efficiency of isolated reaction centres; therefore it is proposed that the mechanism underlying the alumina mediated enhancement of biomass accumulation in L. minor is associated with increased efficiencies in the light reactions of photosynthesis.

Dietary cadmium intake by the Belgian adult population.

The aim of this study was to estimate the dietary cadmium (Cd) intake of the Belgian adult population, to compare this dietary Cd exposure to the tolerable weekly intake (TWI) recently established by the European Food Safety Authority (EFSA) and to determine the major food groups that contribute to dietary Cd exposure in Belgium. Food consumption data were derived from the 2004 Belgian food consumption survey (two 24 h recalls, 3083 participants). Cadmium concentrations in food items (n = 4000) were gathered from the control program of the Belgian Federal Agency for the Safety of the Food Chain for the period 2006-2008. Dietary intake per individual was calculated from consumption data and median Cd concentrations. The population mean, median and 95th percentile of the dietary intake values were 0.98, 0.85 and 2.02 µg kg⁻¹ body weight per week respectively. Two percent of the Belgian adult population has a dietary Cd intake above the recent TWI of 2.5 µg kg⁻¹ body weight established by EFSA in 2009. Cereal products and potatoes contribute for more than 60% to Cd intake.

Evaluating daily exposure to polychlorinated biphenyls and polybrominated diphenyl ethers in fish oil supplements.

Fish oil supplements have become a popular means of increasing one's dietary intake of essential polyunsaturated fatty acids. However, there is growing concern that the levels and potential health effects of lipophilic organic contaminants such as polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs) may diminish some of the health benefits associated with the daily consumption of fish oil supplements. In this study, ten over-the-counter fish oil supplements available in the United States were analysed for PCBs and PBDEs and daily exposures calculated. Based on manufacturers' recommended dosages, daily intakes of PCBs and PBDEs ranged from 5 to 686 ng day(-1) and from 1 to 13 ng day(-1), respectively. Daily consumption of fish oil supplements expose consumers to PCBs and PBDEs. However, in comparison with fish ingestion, fish supplements may decrease daily PCB exposure and provide a safer pathway for individuals seeking to maintain daily recommended levels of polyunsaturated fatty acids.

Testicular toxicity induced by dietary cadmium in cocks and ameliorative effect by selenium.

Cadmium (Cd) is an ubiquitous environmental pollutant that has been associated with male reproductive toxicity in animal models. However, little is known about the reproductive toxicity of Cd in birds. To investigate the toxicity of Cd on male reproduction in birds and the protective effects of selenium (Se) against subchronic exposure to dietary Cd, 100-day-old cocks received either Se (as 10 mg Na(2)SeO(3) per kg of diet), Cd (as 150 mg CdCl(2) per kg of diet) or Cd + Se in their diets for 60 days. Histological and ultrastructural changes in the testis, the concentrations of Cd and Se, amount of lipid peroxidation (LPO), the activities of the antioxidants superoxide dismutase (SOD) and glutathione peroxidase (GPx), and apoptosis and serum testosterone levels were determined. Exposure to Cd significantly lowered SOD and GPx activity, Se content in the testicular tissue, and serum testosterone levels. It increased the amount of LPO, the numbers of apoptotic cells and Cd concentration and caused obvious histopathological changes in the testes. Concurrent treatment with Se reduced the Cd-induced histopathological changes in the testis, oxidative stress, endocrine disorder and apoptosis, suggesting that the toxic effects of cadmium on the testes is ameliorated by Se. Se supplementation also modified the distribution of Cd in the testis.

Acute toxicity of 3,3',4,4',5-pentachlorobiphenyl (PCB 126) in male Sprague-Dawley rats: effects on hepatic oxidative stress, glutathione and metals status.

Although polychlorinated biphenyl (PCBs) production, and new uses for PCBs, was halted in the 1970s in the United States, PCBs continue to be used in closed systems and persist in the environment, accumulating in fatty tissues. PCBs are efficacious inducers of drug metabolism and may increase oxidative events and alter many other biochemical and morphologic parameters within cells and tissues. The goal of the present study was to evaluate the effects of a single, very low dose of PCB 126 (3,3',4,4',5-pentachlorobiphenyl), a coplanar, dioxin-like PCB congener and aryl hydrocarbon receptor (AhR) agonist, on redox status, metals homeostasis, antioxidant enzymes, and cellular morphology. To examine these parameters, male Sprague-Dawley rats were fed a purified AIN-93 basal diet containing 0.2 ppm selenium for two weeks, then administered a single i.p. injection of corn oil (5 ml/kg body weight) or 1µmol PCB 126/kg body weight (326µg/kg body weight) in corn oil. Rats were maintained on the diet for an additional two weeks before being euthanized. This dose of PCB 126 did not alter feed intake or growth, but significantly increased liver weight (42%) and hepatic microsomal cytochrome P-450 (CYP1A) enzyme activities (10-40-fold increase). Hepatic zinc, selenium, and glutathione levels were significantly decreased 15%, 30%, and 20%, respectively, by PCB 126. These changes were accompanied by a 60% decrease in selenium-dependent glutathione peroxidase activity. In contrast, hepatic copper levels were increased 40% by PCB 126. PCB 126-induced pathology was characterized by hepatocellular hypertrophy and mild steatosis in the liver and a mild decrease in cortical T-cells in the thymus. This controlled study in rats fed a purified diet shows that even a single, very low dose of PCB 126 that did not alter feed intake or growth, significantly perturbed redox and metals homeostasis and antioxidant and enzyme levels in rodent liver.

Chronic treatment with polychlorinated biphenyls (PCB) during pregnancy and lactation in the rat: Part 1: Effects on somatic growth, growth hormone-axis activity and bone mass in the offspring.

Polychlorinated biphenyls (PCBs) are pollutants detected in animal tissues and breast milk. The experiments described in the present paper were aimed at evaluating whether the four PCB congeners most abundant in animal tissues (PCB-138, -153, -180 and -126), administered since fetal life till weaning, can induce long-term alterations of GH-axis activity and bone mass in the adult rat. We measured PCB accumulation in rat brain and liver, somatic growth, pituitary GH expression and plasma hormone concentrations at different ages. Finally, we studied hypothalamic somatostatin expression and bone structure in adulthood, following long-term PCB exposure. Dams were treated during pregnancy from GD15 to GD19 and during breast-feeding. A constant reduction of the growth rate in both male and female offspring from weaning to adulthood was observed in exposed animals. Long-lasting alterations on hypothalamic-pituitary GH axis were indeed observed in PCB-exposed rats in adulthood: increased somatostatin expression in hypothalamic periventricular nucleus (both males and females) and lateral arcuate nucleus (males, only) and decreased GH mRNA levels in the pituitary of male rats. Plasma IGF-1 levels were higher in PCB-exposed male and female animals as compared with controls at weaning and tended to be higher at PN60. Plasma testosterone and thyroid hormone concentrations were not significantly affected by exposure to PCBs. In adulthood, PCBs caused a significant reduction of bone mineral content and cortical bone thickness of tibiae in male rat joint to increased width of the epiphyseal cartilage disk. In conclusion, the developmental exposure to the four selected PCB compounds used in the present study induced far-reaching effects in the adult offspring, the male rats appearing more sensitive than females.