Pb Acetate Research Articles

Uncovering the links between osteoporosis and diabetes

Introduction: Using an animal model for osteopenia to describe the distribution of Lead (Pb) throughout the body, we have reported that ovariectomized animals had significantly lower serum osteocalcin (OC) levels and higher, although nonsignificant, serum C-terminal peptide-bound crosslinks of collagen (CTX) levels than intact animals [1]. Here we present unpublished data on concentrations of elements of interest (Ca, Cl, Fe, K, Na and Pb) in hard and soft tissues of the same animals, to uncover the links between osteoporosis and diabetes. The model makes it feasible to investigate such links, therefore the appropriateness of this approach is not only warranted but also justified by the 3RS principle for the use of animals in research. Materials and methods: The animal study was approved by the Ethics Committee of ISCSEM and was conducted following the Portuguese Law and EU Directive 2010/63/EU, in a licensed animal facility. Two groups of adult female Wistar rats of the same age were considered: normal intact rats (n = 7); and OVX animals (n = 7) ovariectomized between the 11th and 12th week of age. From age 6-months on, all animals received the same dose of Pb acetate in water (500 ppm) for 6 months. Tissues collected for analysis included lumbar vertebrae and femora bones, as well as blood and liver. The concentration of elements of interest in hard and soft tissues was determined by Wavelength Dispersive X Ray Fluorescence (WDXRF) spectroscopy, using a 4kW commercial spectrometer (S4 Pioneer, Bruker AXS). Multivariate analysis of variance (MANOVA) was used in group comparisons, given the multiple correlations between elemental concentrations. Results: MANOVA methods show that OVX animals have significantly higher liver Cl, Na and Ca concentrations, whereas normal animals show significantly higher liver Pb and K concentrations, with observed power of 91.0%. Significantly lower serum OC levels were observed in the OVX group, with observed power of 72.7%, with no differences between groups for CTX levels. Lower Ca content was strongly suggested for trabecular bone of OVX animals. Discussion and conclusions: Significant differences in hepatic Ca concentration between OVX and normal animals suggest that Ca signalling mechanisms regulating gluconeogenesis, through modulation of hormones such as glucagon, insulin, vasopressin and adrenalin [2,3], may occur differently in the two groups. Moreover, since extracellular concentrations of cations such as K and Na markedly affect the hormonal activity effects on gluconeogenesis [4], the observed differences in the hepatic concentrations of such elements between the groups may further increase differences in gluconeogenesis in the two groups. Therefore, we postulated that bone turnover changes may impact on gluconeogenesis, which launched the basis for another research project linking osteoporosis to diabetes, nearly concluded in our laboratory.

Chronic lead exposure decreases the expression of Huntingtin-associated protein 1 (HAP1) through Repressor element-1 silencing transcription (REST)

Chronic lead (Pb) exposure has been shown to reduce the expression of some synaptic proteins which are involved in vesicular trafficking and affect presynaptic neurotransmitter release. However, the precise mechanisms by Pb impairs neurotransmitter release are still not well defined. In the current study, we aimed to elucidate the changes of Huntingtin-associated protein 1 (HAP1) in Pb exposed rats and PC12 cells models and its molecular mechanism. Repressor element-1 silencing transcription (REST) modulates the expression of genes containing the repressor element 1 (RE-1) cis-regulatory DNA sequence. HAP1 promoter region contains a RE-1 binding motif. We also observed whether Pb exposure regulated the HAP1 transcription level through influencing the expression of REST. Mother rats were exposed to 0.5 and 2 g/L Pb acetate (PbAc) in drinking water from the first day of gestation until postnatal 21 days, then the offspring rats were continued to drink PbAc for 1 year, while the control groups received drinking water. PC12 cells were divided into 3 groups: 0 μM, 1 μM and 100 μM PbAc. The results revealed that Pb levels in blood and brain of Pb exposed groups were significantly higher than that of the control group. The ability of learning and memory in Pb exposed rats was decreased. Pb exposure reduced the expression of HAP1 and increased the REST expression. Silencing REST could reverse the decreasing of HAP1 in Pb exposed PC12 cells. Our findings raise a possibility that the decreasing of HAP1 expression by Pb exposure may affect neurotransmitter release and results in impairments in spatial learning and memory ability.

Pb exposure reduces the expression of SNX6 and Homer1 in offspring rats and PC12 cells

Lead (Pb) is a widespread environmental heavy metal toxicant and chronic Pb exposure can have irreversible effects on memory and cognitive function, which is closely related to dendritic spines. Studies have shown that SNX6 and Homer1 can regulate the growth of dendritic spines. We aimed to investigate the effect of Pb exposure on the dendritic spines in hippocampus, the expression of SNX6 and Homer1 in rats and PC12 cells. The animals were randomly divided to three groups: control group, low lead group and high lead group. PC12 cells were divided into 3 groups: 0 μM, 1 μM and 100 μM Pb acetate. The results showed that the Pb levels in blood and hippocampus of all exposure groups were significantly higher than that of the control group. The morphology of dendritic spines in hippocampus after Pb treatment was changed and the density of dendritic spines was reduced. The expression of SNX6 and Homer1 was decreased in Pb exposed groups compared with the control group. Furthermore, up-regulation of SNX6 expression could reverse the down-regulation of Pb exposure on Homer1. These results indicate that Pb exposure can reduce the expression of SNX6 and lead to a decrease in Homer1 expression, which affects the changes in dendritic spines causing learning and memory impairment.

Modulation of caspase-3 gene expression and protective effects of garlic and spirulina against CNS neurotoxicity induced by lead exposure in male rats

Lead (Pb) is a ubiquitous environmental and industrial pollutant with worldwide health problems. The present study was designed to investigate the neurotoxic effects of Pb in albino rats and to evaluate the ameliorative role of garlic as well as Spirulina maxima against such toxic effects. Forty adult male rats were used in this investigation (10 rats/group). Group I: served as control, Group II: rats received lead acetate (100 mg/kg), Group III: rats received both lead acetate (100 mg/kg) and garlic (600 mg/kg) and Group IV: rats received both lead acetate (100 mg/kg) and spirulina (500 mg/kg) daily by oral gavage for one month. Exposure to Pb acetate adversely affected the measured acetyl cholinesterase enzyme activity, oxidative stress and lipid peroxidation parameters as well as caspase-3 gene expression in brain tissue (cerebrum and cerebellum). Light and electron microscopical examination of the cerebrum and cerebellum showed various lesions after exposure to Pb which were confirmed by immunohistochemistry. On the other hand, administration of garlic and spirulina concomitantly with lead acetate ameliorated most of the undesirable effects. It could be concluded that, the adverse effects induced by lead acetate, were markedly ameliorated by co-treatment with S. maxima more than garlic.

Selenium-Yeast Alleviated Inflammatory Damage Caused by Lead via Inhibiting Ras/ERK Pathway and Inflammatory Factors in Chicken Skeletal Muscles.

The aim of this study was to investigate the ameliorative effects of selenium-enriched yeast (Se-yeast) on the inflammatory damage induced by lead (Pb) in chicken skeletal muscles. A total of 108 1-day-old broiler chickens were randomly allocated into four groups (n = 27/group): the control group (C group), the Se-yeast-supplemented group (Se group), the lead-treated group (Pb group), and finally the Se- and Pb-combined group (Pb/Se group). The C group was fed with a basic diet comprising 0.049mg/kg Se and 0.1mg/kg Pb while the Se group was fed a Se-yeast diet containing 0.30mg/kg Se and 0.1mg/kg Pb. Similarly, the Pb group was fed a Pb acetate diet containing 0.049mg/kg Se and 350mg/kg Pb while the Pb/Se group was fed with a Se-yeast diet containing 0.30mg/kg Se and 350mg/kg Pb. On days 7, 21, and 35 after commencing the experiment, nine chicks belonging to each group were euthanized and the samples were analyzed by employing the techniques of inductively coupled plasma mass spectrometry and real-time quantitative PCR, along with Western blotting. The results indicated that excess Pb increased the nitric oxide concentration, enhanced the activity of inducible nitric oxide synthase (iNOS), and the mRNA levels of interleukin 1β (IL-1β), interleukin 4 (IL-4), interleukin 10 (IL-10), and interferon gamma (IFN-γ) in a time-dependent manner. Further, it was found that Se reduced damage caused by Pb by decreasing the expression of inflammatory factors in chicken skeletal muscles. Taken together, the results from this study provide the theoretical basis for an alleviate effect of Se on Pb-induced inflammatory damage in chicken skeletal muscles, mediated by inhibiting the Ras/extracellular signal-regulated kinase (ERK) pathway and the inflammatory factors.

Effects of ascorbic acid treatment on developmental alterations in calcium-binding proteins and gamma-aminobutyric acid transporter 1 in the cerebellum of lead-exposed rats during pregnancy and lactation.

In the present study, we investigated the effects of lead (Pb) and ascorbic acid co-administration on rat cerebellar development. Female rats were randomly divided into the following groups: control, Pb, and Pb plus ascorbic acid (PA) groups. From one week prior to mating, female rats were administered Pb (0.3% Pb acetate in drinking water) and ascorbic acid (100 mg/kg, oral intubation). The chemical administration was stopped on postnatal day 21 when the morphology of the offspring's cerebellum is similar to that of the adult brain. The blood Pb level was significantly increased following long-term Pb exposure. Ascorbic acid reduced Pb levels in the dams and offspring. Nissl staining demonstrated that the number of Purkinje cells was significantly reduced following Pb exposure, while ascorbic acid ameliorated this effect in the cerebellum of the offspring. Calcium-binding proteins, such as calbindin, calretinin, and parvalbumin were commonly expressed in Purkinje cells, and Pb exposure and ascorbic acid treatment resulted in similar patterns of change, namely Pb-induced impairment and ascorbic acid-mediated amelioration. The gamma-aminobutyric acid transporter 1 (GABAT1) is expressed in the pinceau structure where the somata of Purkinje cells are entwined in inhibitory synapses. The number of GABAT1-immunoreactive synapses was reduced following Pb exposure, and ascorbic acid co-treatment prevented this effect in the cerebellar cortex. Therefore, it can be concluded that ascorbic acid supplementation to mothers during gestation and lactation may have potential preventive effects against Pb-induced impairments in the developing cerebellum via protection of inhibitory neurons and synapses.

Enhanced remedial effects for vitamin D3 and calcium co-supplementation against pre-existing lead nephrotoxicity in mice: The roles of renal calcium homeostatic molecules

BackgroundLead (Pb) is a toxic heavy metal and nephropathy is common with chronic exposure. Although vitamin D (VD) and calcium (Ca) showed promising protections, their co-administration was not previously investigated in Pb nephrotoxicity. This study measured the potential interactions and remedial effects of VD and/or Ca on established Pb nephropathy. MethodsFifty adult male mice were equally distributed into: negative controls (NC), positive controls (PC), Ca, VD and VDC groups. The study duration was seven weeks and all groups, except the NC, received Pb acetate in drinking water (500 mg/L) throughout the study. The Ca, VD and VDC groups also received oral Ca (50 mg/kg; five times/week) and/or intramuscular VD (1000 IU/kg; three times/week) from week four till the end of the study. ResultsThe PC group showed substantial reduction in serum VD, hypocalcaemia, hypercalciuria and proteinuria alongside marked tissue inflammation, oxidative stress and apoptosis/necrosis. Pathological alterations were also detected in the mRNAs and proteins of the VD-metabolising enzymes, receptor and binding protein alongside several Ca-membrane channels, membrane transporters, intracellular binding proteins and mediators. While both monotherapies equally demonstrated moderate improvements, the VDC showed the utmost corrective actions on serum and tissue Pb concentrations, the inflammatory and antioxidative markers, the expressions of renal VD/Ca-molecules and tissue integrity. Moreover, the results were comparable between the VDC and NC groups. ConclusionsThis report is the first to reveal potential enhanced remedial outcomes for combining VD and Ca against pre-existing Pb nephrotoxicity and the enhancements could be dependent on Ca-regulatory pathways.

Ascorbic Acid Supplementation Prevents the Detrimental Effects of Prenatal and Postnatal Lead Exposure on the Purkinje Cell and Related Proteins in the Cerebellum of Developing Rats.

We investigated the effects of lead (Pb) and ascorbic acid co-administration on rat cerebellar development. Prior to mating, rats were randomly divided into control, Pb, and Pb plus ascorbic acid (PA) groups. Pregnant rats were administered Pb in drinking water (0.3% Pb acetate), and ascorbic acid (100mg/kg) via oral intubation until the end of the experiment. Offspring were sacrificed at postnatal day 21, the age at which the morphology of the cerebellar cortex in developing pups is similar to that of the adult brain. In the cerebellum, Pb exposure significantly reduced Purkinje cells and ascorbic acid prevented their reduction. Along with the change of the Purkinje cells, long-term Pb exposure significantly reduced the expression of the synaptic marker (synaptophysin), γ-aminobutyric acid (GABA)-synthesizing enzyme (glutamic acid decarboxylase 67), and axonal myelin basic protein while ascorbic acid co-treatment attenuated Pb-mediated reduction of these proteins in the cerebellum of pups. However, glutamatergic N-methyl-D-aspartate receptor subtype 1 (NMDAR1), anchoring postsynaptic density protein 95 (PSD95), and antioxidant superoxide dismutases (SODs) were adversely changed; Pb exposure increased the expression of NMDAR1, PSD95, and SODs while ascorbic acid co-administration attenuated Pb-mediated induction. Although further studies are required about the neurotoxicity of the Pb exposure, the results presented here suggest that developmental Pb exposure disrupted normal development of Purkinje cells by increasing glutamatergic and oxidative stress in the cerebellum. Additionally, ascorbic acid co-treatment is beneficial in attenuating prenatal and postnatal Pb exposure-induced maldevelopment of Purkinje cells in the developing cerebellum.

Early chronic exposure to low-level lead alters total hippocampal microglia in pre-adolescent mice

Developmental lead (Pb) exposure alters brain function through mechanisms that are not yet understood. A previous study showed that early lead exposure reduced microglia number in the dentate gyrus region of the hippocampus. Given the critical role of microglia in brain development, it is important to determine whether these differences are unique to the dentate gyrus, or occur throughout the hippocampus. Unbiased stereology was used to quantify microglia mean cell body number in total hippocampus, and compare the proportion of microglia in the ventral vs. dorsal regions. Total hippocampal volume was also measured and compared. The study included brain tissue from 30 pre-adolescent C57BL/6 J mice, exposed to 30 ppm Pb acetate (n = 10, mean BLL 3.4 μg/dL at sacrifice), 330 ppm Pb acetate (n = 10, mean BLL 14.1 μg/dL at sacrifice), or 0 ppm Pb acetate (n = 10, negative controls). In lead exposed animals, microglia mean cell body number was reduced in total hippocampus; total hippocampal volume was reduced. Importantly, effects in low- and high-dose exposure groups did not differ. Contrary to study hypotheses, the distribution of hippocampal microglia in the ventral vs. dorsal hippocampal regions did not differ. Overall, lowest and higher levels of lead exposure during development had strikingly similar disruptive effects in the neuroimmune system. Studies are needed to determine the immune and other mechanisms responsible for these effects. Future studies would benefit from larger samples to determine whether in fact there is a group by sex interaction driving the effects of early lead exposure on microglia.

Thymoquinone attenuates lead-induced nephropathy in rats.

Kidney hazards from lead (Pb) exposure are one of the fastest growing areas of concern in toxicology today. The thymoquinone (TQ) renoprotective effect against Pb-induced nephropathy has not previously been studied. Therefore, adult male Wistar rats were treated with Pb (2000 ppm of Pb acetate in drinking water) and/or TQ (5 mg/kg/day, per os). All treatments were applied for 5 weeks. The results indicated that Pb exposure produced metal deposition, histopathological changes, functional impairment (significant elevation in plasma urea, uric acid, and creatinine levels), total antioxidant status decrease, and lipid peroxidation stimulation in the kidneys. Interestingly, TQ supplementation remarkably improved the Pb-induced renal adverse effects without significantly reducing the tissue metal accumulation. In conclusion, our data indicate for the first time a protective effect of TQ against Pb-induced nephropathy, most likely through an antioxidant mechanism. On this basis, TQ deserves more consideration and further examination as a potential therapeutic option.

ANTIOXIDANT ACTIVITY OF ETHYL ACETATE FRACTION OF MACARANGA TRILOBA LEAVES FROM CENTRAL KALIMANTAN

Objective: Macaranga triloba was used by the local for diabetes, antidiabetes have strong relation with antioxidant activity, antioxidants have been shown to prevent the destruction of β-cells by inhibiting the preoxidation chain reaction, plants containing natural antioxidant (like flavonoid and alkaloid) can protect β cell function. So the objective of this study is to investigate antioxidant activity of ethyl acetate fraction of Macaranga triloba leaves and did preliminary phytochemical screening (Alkaloid and Flavonoid).Methods: Macaranga triloba leaves (Mahang damar) were collected from the local areas of Bukit Rawi Central Kalimantan. Macaranga triloba leaves were extracted using maceration methods, followed by fractionation using liquid-liquid extraction methods starting from n-hexane, ethyl acetate, methanol but in this research used ethyl acetate fraction of Macaraga triloba and preliminary phytochemical screening for alkaloid used dragendorff and flavonoid used Pb Acetate. Antioxidant activity test was carried out using 1,1-diphenyl-2-pikrilhidrazil (DPPH) with quercetin as a reference.Results: It was found that ethyl acetate fraction of Macaranga triloba leaves containing positive flavonoid that has been shown by dragendorff methode (brick red sedimen) and positive alkaloid by Pb acetate. The inhibition concentration 50 (IC50) value of ethyl acetate fraction of Macaranga triloba leaves is 56.93 ppmConclusion: Macaranga triloba leaves by preliminary screening of phytochemical containing alkaloid and flavonoid. Antioxidant activity of ethyl acetate fraction with IC50 = 56.93 ppm is weaker than quercetin (IC50 = 4.46 ppm), but still in range value of strong antioxidant activity (50-100 ppm)

Beneficial Effects of Curcumin in Maternal and Fetal Oxidative Stress and Brain Damage Induced by Gestational Lead Administration

This study was planned to explore the protective role of curcumin (Cur) against maternal and fetal oxidative stress and cerebral damage induced by lead (Pb) during pregnancy. Positively pregnant female rats were divided into seven groups: control group, Cur group (300 mg/kg of Cur/b.wt.), DMSO group (50% DMSO), two Pb-treated groups (exposed to 160 and 320 mg/kg b.wt./day of Pb acetate, respectively), and two groups treated with both Pb and Cur (exposed to Pb as previous groups together with 300 mg/kg b.wt./day of Cur). Treatments through oral gavage once a day started from gestation day 1 (GD1) till day 20 (GD20), where the mother rats of different experimental groups were sacrificed to obtain the fetuses. Different chemical parameters were assessed. Brain specimens of mother and fetal groups were processed with examination. The results displayed that Pb administration to pregnant rats resulted in a dose-dependent toxicity for both mothers and fetuses. Also, there was a significant rise in lipid peroxidation and decreased antioxidant enzyme activities in the brains of the different Pb-treated groups. The histological examination of the brain of treated dams and fetuses showed marked alterations. Co-treatment of Cur along with Pb caused a significant decrease in Pb levels as compared with those treated with Pb alone, improving the oxidative condition with amelioration of the brain’s histopathological changes. Co-administration of Cur could have ameliorative effect against Pb-induced neurotoxicity through the reduction of oxidative stress and reversal of histopathological changes.

Impact of excess lead on the stability and photo-induced degradation of lead halide perovskite solar cells

Abstract The stability of perovskite solar cells exposed to prolonged solar irradiation is a major concern that has not been thoroughly investigated in the past. In this investigation, devices fabricated with the architecture, glass/ITO/PEDOT:PSS/MAPbI3/PCBM/Ag using Pb acetate as a source material, were found to operate with an efficiency of about 13%. Adding excess amounts of Pb to the precursor resulted in a presence of Pb in the perovskite (PVS) active layer. In addition, the impact of photo-induced degradation on the device efficiency was investigated. X-ray Diffraction and Time-resolved Photoluminescence analyses were used to evaluate the impact of excess Pb before and after illumination. The results indicate that changes in the crystallinity occur without any significant decrease in charge carrier lifetimes, and this is attributed to the formation of the degradation product, PbI2. This by-product has been shown to have beneficial effects due to its influence in passivating grain boundaries and in altering the band structure at the interface between the active layer and the electron transport layer. This work demonstrates that 5 mol% excess Pb is the optimal concentration with respect to efficiency and stability of these devices. The devices can retain more than 50% of their initial efficiency after 1 h of simulated solar exposure, when compared to 0 mol% and 10 mol% excess Pb samples.

Ascorbic Acid Attenuates Lead-Induced Alterations in the Synapses in the Developing Rat Cerebellum.

We evaluated the effect of lead (Pb) and ascorbic acid treatment of pregnant female rats on cerebellar development in pups. Pb was administered in drinking water (0.2% Pb acetate), and ascorbic acid (100mg/kg) was administered through oral intubation. Fifteen female rats were randomly classified into control, Pb, and Pb plus ascorbic acid (PA) groups. The treatment of Pb and ascorbic acid treatments were terminated after birth to evaluate the effects on the gestational development of the cerebellum. At postnatal day 21 (PND21), pups were sacrificed, and blood Pb level was analyzed. Blood Pb levels of pups and dams were highest in the Pb group and reduced in the PA group. Immunohistochemistry and immunoblot assays were conducted to study the cerebellar expression levels of synaptic proteins. Along with a significant reduction in Purkinje cells, the reduction in presynaptic (synaptophysin) and postsynaptic (postsynaptic density protein 95, N-methyl-D-aspartate receptor subtype 1) marker proteins was observed in Pb-exposed pups. Ascorbic acid treatment significantly prevented Pb-induced impairment in the cerebellar synaptic proteins. Hypothesizing that brain-derived neurotrophic factor (BDNF) might be affected by Pb exposure given its importance in the regulation of synaptogenesis, we observed a Pb-induced decrease and ascorbic acid-mediated increase of BDNF in the cerebellum. Luxol fast blue staining and myelin basic protein analysis suggest that ascorbic acid treatment ameliorated the Pb exposure-induced reduction in the axonal fibers in the developing cerebellum. Overall, we conclude that ascorbic acid treatment during pregnancy can prevent Pb-induced impairments in the cerebellar development in rats.

Formation of solid solutions via solid-state lead diffusion in chemically deposited CdS films

Substitutional solid solutions in the CdS–PbS system were obtained by aging of chemically deposited cadmium sulfide thin film in an aqueous solution of lead acetate Pb(C2H3O2)2. By using the thermodynamic calculations a possibility of proceeding of a heterogeneous ion-exchange reaction at the interface “chemically deposited CdS film/lead salt aqueous solution” was estimated. The effect of solid-state diffusion on the morphology, composition, and optical properties of the CdS films was investigated. By means of X-ray photoelectron spectroscopy with layer-by-layer sputtering, the chemical composition across the obtained films thickness was analyzed, and concentration depth profiles of the elements were plotted. The coefficient of the lead diffusion into the cadmium sulfide film during its ion-exchange transformation was calculated.

Therapeutic effect of thymoquinone against lead-induced testicular histological damage in male Wistar rats.

Lead (Pb) is a nonthreshold multi-targeted toxicant that causes alterations in different organs of the body, especially the gonads. This study was aimed to investigate the possible protective effect of thymoquinone (TQ), the major active ingredient of volatile oil of Nigella sativa seeds, against Pb-induced testicular histological damage. Adult male rats were randomised into four groups as follows: control group received no treatment, Pb group was exposed to 2000ppm of Pb acetate in drinking water, Pb-TQ group was cotreated with Pb plus TQ (5mg/kg/day, per os) and TQ group receiving only TQ. All treatments were applied for five weeks. Results showed that Pb exposure produced morphological changes in the testis, especially degeneration of germinal epithelium, sloughing of germ cells into the lumen of seminiferous tubules and reduction in the number of luminal spermatozoa. Interestingly, coadministration of TQ to the metal-treated animals prevented the testicular adverse effects. In conclusion, our data indicate for the first time a remarkable protective effect of TQ against Pb-induced testicular histopathological lesions in rat. On this basis, TQ deserves more consideration and further examination as a potential therapeutic option.

Developmental Lead Exposure and Prenatal Stress Result in Sex-Specific Reprograming of Adult Stress Physiology and Epigenetic Profiles in Brain.

Developmental exposure to lead (Pb) and prenatal stress (PS) both impair cognition, which could derive from their joint targeting of the hypothalamic-pituitary-adrenal axis and the brain mesocorticolimbic (MESO) system, including frontal cortex (FC) and hippocampus (HIPP). Glucocorticoids modulate both FC and HIPP function and associated mediation of cognitive and other behavioral functions. This study sought to determine whether developmental Pb ± PS exposures altered glucocorticoid-related epigenetic profiles in brain MESO regions in offspring of female mice exposed to 0 or 100 ppm Pb acetate drinking water from 2 mos prior to breeding until weaning, with half further exposed to prenatal restraint stress from gestational day 11-18. Overall, changes in females occured in response to Pb exposure. In males, however, Pb-induced neurotoxicity was modulated by PS. Changes in serum corticosterone levels were seen in males, while glucocorticoid receptor changes were seen in both sexes. In contrast, both Pb and PS broadly impacted brain DNA methyltransferases and binding proteins, particularly DNMT1, DNMT3a and methyl-CpG-binding protein 2, with patterns that differed by sex and brain regions. Specifically, in males, effects on FC epigenetic modifiers were primarily influenced by Pb, whereas extensive changes in HIPP were produced by PS. In females, Pb exposure and not PS primarily altered epigenetic modifiers in both FC and HIPP. Collectively, these findings indicate that epigenetic mechanisms may underlie associated neurotoxicity of Pb and of PS, particularly associated cognitive deficits. However, mechanisms by which this may occur will be different in males versus females.

Selenium nanoparticles prevents lead acetate-induced hypothyroidism and oxidative damage of thyroid tissues in male rats through modulation of selenoenzymes and suppression of miR-224

Selenium nanoparticles (Se-NPs) are customizable drug delivery vehicles that show good bioavailability, higher efficacy and lower toxicity than ordinary Se. Pre-treatment of male rats with these NPs has been recently shown to exert a protective effect against chromium-induced thyroid dysfunction. This study, therefore, aimed to investigate and characterize the potential protective mechanism of Se-NPs against lead (Pb) acetate-induced thyrotoxicity. We found that prophylactic and concurrent treatment of Pb acetate-exposed rats with Nano-Se (0.5 mg/kg, i.p) for 15 wk significantly alleviated the decrease in free triiodothyronine (fT3) and free thyroxine (fT4) levels as well as fT3/fT4 ratio% and the increase in thyroid stimulating hormone (TSH) levels to approach control values. This was accompanied by a reduction in the accumulation of Pb in serum and thyroid tissues as well as maintenance of thyroidal pro-oxidant/antioxidant balance and iodothyronine deiodinase type 1 (ID1), an essential enzyme for metabolizing of T4 into active T3, gene expression. Surprisingly, miR-224, a direct complementary target of ID1 mRNA, expression in the thyroid tissues was significantly down-regulated in Nano-Se-pre- and co-treated Pb acetate intoxicated animals. Such changes in miR-224 expression were negatively correlated with the changes in ID1 gene expression and serum fT3 level. These results suggest that Se-NPs can rescue from Pb-induced impairment of thyroid function through the maintenance of selenoproteins and down-regulation of miR-224.

The effects of lead exposure on the expression of HMGB1 and HO-1 in rats and PC12 cells

Lead (Pb) is an environmental neurotoxic metal. Chronic exposure to Pb causes deficits of learning and memory in children and spatial learning deficits in developing rats. In this study we investigated the effects of Pb exposure on the expression of HMGB1 and HO-1 in rats and PC12 cells. The animals were randomly divided to three groups: control group; low lead exposure group; high lead exposure group; PC12 cells were divided into 3 groups: 0 μM (control group), 1 μM and 100 μM Pb acetate. The results showed that Pb levels in blood and brain of Pb exposed groups were significantly higher than that of the control group (p < 0.05). The expression of HMGB1 and HO-1 were increased in Pb exposed groups than that of the control group (p < 0.05). Moreover, we found that the up-regulation of HO-1 in Pb exposure environment inhibited the expression of HMGB1.

Lead inhalation and hepatic damage: Morphological and functional evaluation in mice.

Lead (Pb) is a heavy metal that plays an unknown biological role and is very toxic even at low concentrations. The main sources of Pb are Pb-contaminated areas in industrial areas or landfills. Inhalation is one of the most common routes of exposure to this metal, but there is little information on its effect on the liver. Thirty male mice were exposed to 0.1 M Pb acetate by inhalation for 8 weeks, twice a week for 1h. A recovery group was free of exposure for 4 weeks. Histological evaluation showed an increase in the inflammatory infiltrate and in the percentage of meganuclei in the liver. This was observed since the first week and throughout the whole exposure time. A significant increase in the aspartate aminotransferase concentration was observed in the liver function tests; yet, the alanine aminotransferase concentration did not show significant changes. The 4-hydroxynonenal (4-HNE) and nitrotyrosine levels in Pb-exposed mice, identified by immunohistochemistry, showed a significant increment compared to the controls. This effect was observed throughout Pb exposure. After a 4-week period of suspended exposure, recovery time, the concentration of 4-HNE and nitrotyrosine decreased to similar levels of those previously observed in controls, this suggests a decrease in the generation of oxidative stress by Pb inhalation. Although our results suggest that the lungs are the first contact organs and filters during Pb inhalation, this metal eventually reaches the liver and might cause damage by oxidative stress. This damage can decrease in time if exposure is discontinued.