Pb Poisoning Research Articles

Evaluation of Analytes Characterized with Potential Protective Action after Rat Exposure to Lead.

Lead (Pb) was revealed for its role as a neurodevelopmental toxin. The determination of neurotransmitters (NTs) in particular brain regions could ameliorate the precise description and optimization of therapeutic protocols able to restore the harmony of signaling pathways in nervous and immune systems. The determination of selected analytes from the group of NTs based on the liquid chromatography (LC)-based method was carried out to illustrate the changes of amino acid (AA) and biogenic amine (BA) profiles observed in chosen immune and nervous systems rat tissues after Pb intoxication. Also, a protective combination of AA was proposed to correct the changes caused by Pb intoxication. After the administration of Pb, changes were observed in all organs studied and were characterized by a fluctuation of NT concentrations in immune and nervous systems (hypothalamus samples). Using a protective mixture of bioactive compounds prevented numerous changes in the balance of NT. The combined analysis of the immune and nervous system while the normalizing effect of curative agents on the level of differentially secreted NTs and AA is studied could present a new approach to the harmonization of those two essential systems after Pb intoxication.

Neuroprotective effects of vitamin C and garlic on glycoconjugates changes of cerebellar cortex in lead-exposed rat offspring

The deteriorating effects of Lead (Pb) on central nervous system (CNS) such as cerebellum has been demonstrated in previous studies. Glycoconjugates with the important role in CNS development may be affected by Pb-exposure. Utilization of antioxidant agents and herbal plants has attracted a great deal of attention on attenuating neurotoxicants-induced damage. Thus, in this study the neuroprotective effects of vitamin C and garlic on content of glycoconjugates of cerebellar cortex in Pb-exposed animals were investigated. Wistar pregnant rats were divided into: control (C), Pb-exposed (Pb) (1500 ppm lead acetate in drinking water), Pb plus vitamin C (Pb + Vit C) (500 mg/kg) intraperitoneally, Pb plus garlic (Pb + G) (1 mL /100 g body weight fresh garlic juice via gavage), Pb plus vitamin C and garlic (Pb + Vit C + G), and sham groups (Sh). Finally, levels of Pb in blood were measured in both rats and offspring on postnatal day 50 (PND50). Also, the cerebellums were removed for measuring Pb-levels and performing lectin histochemistry. Blood and cerebellar Pb-levels were increased in Pb-exposed group compared to control group (P < 0.001), whereas they were decreased significantly in Pb + Vit C, Pb + G, and Pb + Vit C + G groups (P < 0.01). By using MPA, UEA-1, and WGA lectin histochemistry, Pb-exposed group showed weak staining intensity compared to other groups. Besides, significant decrease was observed in the density of lectin-positive neurons of Pb-exposed group compared to the control group (P < 0.001). Moreover, strong staining intensity and high lectin-positive neurons were found in Pb + Vit C, Pb + G and Pb + Vit C + G groups than Pb-exposed group (P < 0.001). The present study revealed that Pb-exposure can result in alteration in the cerebellar glycoconjugates contents and co-administration of vitamin C and garlic could attenuate the adverse effects of Pb. The findings of this study revealed the ameliorating effects of vitamin C and garlic against Pb, suggesting the potential use of vitamin C and garlic as preventive agents in Pb poisoning.

Histoarchitectural Changes in the Liver Following Lactational Lead Intoxication in Sprague Dawley Rats

The present experiment was designed to study the histoarchitectural changes in the liver following lactational lead (Pb) intoxication in rats. A total of 12 adult female and 4 male rats were used in the experiment and 32 offspring for the analysis of lactational lead intoxication. The offspring were divided into four groups. Groups B, C and D were administered 10 mg/dL, 30 mg/dL and 70 mg/dL of lead acetate respectively, via drinking water for 21 days through the lactating mothers while group A was control. The livers of the pups were observed using histological methods. One-way ANOVA was used to analyze data, followed by Tukey post hoc test for multiple comparisons. The results from the analysis showed that the total body weight, body length and liver weights were only slightly altered in the Pb intoxicated groups. Using relative liver weights alone revealed some form of hepatomegaly among the experimental groups. The results revealed a dose-dependent increase in blood lead concentration. Histopathological evidences revealed moderate to severe histoarchitectural distortions along Pb concentration gradient. Lactational lead intoxication portends dose dependent histopathological changes in the liver of SD rats.

Cognitive Impairment Induced by Lead Exposure during Lifespan: Mechanisms of Lead Neurotoxicity.

Lead (Pb) is considered a strong environmental toxin with human health repercussions. Due to its widespread use and the number of people potentially exposed to different sources of this heavy metal, Pb intoxication is recognized as a public health problem in many countries. Exposure to Pb can occur through ingestion, inhalation, dermal, and transplacental routes. The magnitude of its effects depends on several toxicity conditions: lead speciation, doses, time, and age of exposure, among others. It has been demonstrated that Pb exposure induces stronger effects during early life. The central nervous system is especially vulnerable to Pb toxicity; Pb exposure is linked to cognitive impairment, executive function alterations, abnormal social behavior, and fine motor control perturbations. This review aims to provide a general view of the cognitive consequences associated with Pb exposure during early life as well as during adulthood. Additionally, it describes the neurotoxic mechanisms associated with cognitive impairment induced by Pb, which include neurochemical, molecular, and morphological changes that jointly could have a synergic effect on the cognitive performance.

Application of Stable Isotopic Ratio Analysis to Identify the Cause of Acute Versus Chronic Lead Poisoning of a Tundra Swan (Cygnus columbianus): A Case Study.

We utilized lead (Pb) stable isotopes to identify the source of acute Pb poisoning in a Tundra Swan (Cygnus columbianus) and evaluated overall Pb exposure. Upon necropsy, we obtained samples of blood, liver, kidney, heart, thigh, breast, femur, and metallic objects (i.e., fishing sinker, spring and swivels) from the gizzard for Pb isotopic analysis. Pb isotope ratios of blood and soft tissues were essentially identical to the Pb ratios of the sinker, the likely source of acute poisoning. The spring and swivels had lower Pb content and ratios distinct from tissue, suggesting no significant contribution to poisoning. Femur Pb isotopic composition was the most distinct biological sample and indicative of a combination of sources. These results demonstrate isotopic analysis as a viable method for determining the source of acute Pb poisoning, and that Pb isotope ratios in bone most likely record a lifetime-averaged metric of Pb exposure.

The impact of environmental lead exposure on Whooper swan (Cygnus cygnus): Pathological and immunohistochemical studies

This study was carried out to investigate the pathology of environmental lead (Pb) poisoning in Whooper swans (Cygnus cygnus). A number of 12 out 54 swans (22.2%) randomly collected from Honshu, Japan from June 2005 to July 2007 were affected with Pb poisoning. Affected swans showed stained vent with greenish watery diarrhoea and impacted crop. The presence of Pb shots in the gizzard (50%) was confirmed by X-ray, and all cases showed a dark greenish coloured liver. Microscopically, the pathology of Pb poisoning in swans was multisystemic. The severity of the lesions was the highest in the CNS followed by the liver, kidney, spleen, lungs, gizzard, heart, bone marrow respectively and was the least in the peripheral nervous system. CNS lesions were cerebral haemorrhage, malacia, and spongiosis with astrocytic activation and increased neurofilaments accumulations. In addition, there were hepatic and renal hemosiderosis and apoptosis, hepatic granuloma, interstitial pneumonia, gizzard and myocardial necrosis and bone marrow hypoplasia. Chemical analysis of the Pb content in liver and kidneys ranged from 8.18 to 60.6 µg/g, respectively. The extent and severity of lesions varied among individuals and were mostly dose-dependent. Finally, these findings improved the diagnostic procedure of Pb poisoning in free-living Whooper swans.

Lead-Induced Motor Dysfunction Is Associated with Oxidative Stress, Proteome Modulation, and Neurodegeneration in Motor Cortex of Rats.

Lead (Pb) is a toxic metal with great neurotoxic potential. The aim of this study was to investigate the effects of a long-term Pb intoxication on the global proteomic profile, oxidative biochemistry and neuronal density in motor cortex of adult rats, and the possible outcomes related to motor functions. For this, Wistar rats received for 55 days a dose of 50 mg/Kg of Pb acetate by intragastric gavage. Then, the motor abilities were evaluated by open field and inclined plane tests. To investigate the possible oxidative biochemistry modulation, the levels of pro-oxidant parameters as lipid peroxidation and nitrites were evaluated. The global proteomic profile was evaluated by ultraefficiency liquid chromatography system coupled with mass spectrometry (UPLC/MS) followed by bioinformatic analysis. Moreover, it was evaluated the mature neuron density by anti-NeuN immunostaining. The statistical analysis was performed through Student's t-test, considering p < 0.05. We observed oxidative stress triggering by the increase in malonaldehyde and nitrite levels in motor cortex. In the proteomic analysis, the motor cortex presented alterations in proteins associated with neural functioning, morphological organization, and neurodegenerative features. In addition, it was observed a decrease in the number of mature neurons. These findings, associated with previous evidences observed in spinal cord, cerebellum, and hippocampus under the same Pb administration protocol, corroborate with the motor deficits in the rats towards Pb. Thus, we conclude that the long-term administration to Pb in young Wistar rats triggers impairments at several organizational levels, such as biochemical and morphological, which resulted in poor motor performance.

(Ascorb)ing Pb Neurotoxicity in the Developing Brain.

Lead (Pb) neurotoxicity is a major concern, particularly in children. Developmental exposure to Pb can alter neurodevelopmental trajectory and has permanent neuropathological consequences, including an increased vulnerability to further stressors. Ascorbic acid is among most researched antioxidant nutrients and has a special role in maintaining redox homeostasis in physiological and physio-pathological brain states. Furthermore, because of its capacity to chelate metal ions, ascorbic acid may particularly serve as a potent therapeutic agent in Pb poisoning. The present review first discusses the major consequences of Pb exposure in children and then proceeds to present evidence from human and animal studies for ascorbic acid as an efficient ameliorative supplemental nutrient in Pb poisoning, with a particular focus on developmental Pb neurotoxicity. In doing so, it is hoped that there is a revitalization for further research on understanding the brain functions of this essential, safe, and readily available vitamin in physiological states, as well to justify and establish it as an effective neuroprotective and modulatory factor in the pathologies of the nervous system, including developmental neuropathologies.

Heavy metal poisoning resistance of a Co-modified 3Mn10Fe/Ni low-temperature SCR deNOx catalyst.

Heavy metals have a great influence on the deNOx efficiency of catalysts. The 3Mn10Fe/Ni catalyst that used nickel foam (Ni) as the carrier, Mn and Fe as the active components, and Co as a trace auxiliary was prepared using an impregnation method. The catalysts poisoned by Pb or Zn and Co-modified catalysts with Pb or Zn poisoning were studied. The addition of Pb or Zn significantly decreases the deNOx activity of the 3Mn10Fe/Ni catalyst due to the decrease in the content of high-valence metal elements such as Fe3+ and Mn4+, lattice oxygen concentration, reduction performance, acidity, and the number of acid sites. However, after Co modification, the deNOx activity of the poisoned catalysts can be improved effectively because the strong interaction between Pb or Zn and lattice oxygen is weakened, and the contents of lattice oxygen, high valence metal elements, reduction ability, and the number of acid sites increase.

Rare cases of severe life-threatening lead poisoning due to accident or chronic occupational exposure to lead and manganese: Diagnosis, treatment, and prognosis

Chronic long-term, low-dose environmental and occupational exposure to lead (Pb) has been extensively studied in large cohorts worldwide among general populations, miners, smelters, or battery workers. However, studies on severe life-threatening Pb poisoning due to accidental or chronic occupational exposure to Pb and manganese (Mn) were rarely reported. We present one case of acute severe Pb poisoning and compare it with another severe chronic occupational exposure case involving Pb and Mn. A 27-year-old woman mistakenly took a large quantity of pure Pb powder as an herbal remedy; she developed abdominal colic, severe nausea, vomiting, fatigue, and cutaneous and sclera icterus. Laboratory tests showed her blood lead level (BLL) of 173.5 µg dL-1 and urinary lead level (ULL) of 1240 µg dL-1. The patient was diagnosed with acute Pb poisoning and acute liver failure. In another chronic exposure case, a 56-year-old man worked in a Pb and Mn smelting factory for 15 years. He was brought to the emergency room with severe nausea, vomiting, and paroxysmal abdominal colic, which was intolerable during the onset of pain. His BLL was 64.8 µg dL-1 and ULL was 38 µg dL-1, but his blood and urinary Mn levels were normal. The patient was diagnosed with chronic Pb poisoning. Both patients received chelation therapy with calcium disodium ethylene-diamine-tetraacetate (CaNa2EDTA). The woman with acute severe Pb intoxication recovered well and was discharged from the hospital after treatment, and the man who survived severe Pb poisoning was diagnosed with lung cancer. Clinical manifestations of acute and chronic severe Pb poisoning are different. Chelation therapy with CaNa2EDTA is proven to be an effective life-saving therapy in both cases by reducing BLL. Occupational exposure to both Pb and Mn does not appear to increase Mn neurotoxicity; however, the probability that co-exposure to Mn may increase Pb toxicity in the same patient cannot be excluded.

Ameliorative effects of deferiprone and tetraethylammonium salt of salinomycinic acid on lead-induced toxicity in mouse testes.

In this study, we compare the effects of deferiprone (Def) and tetraethylammonium salt of salinomycinic acid (Sal) on lead (Pb)-induced toxicity in testes of Pb-exposed mice. Mature male ICR mice were allocated into four groups as follows: untreated control mice (ctrl)-received distilled water for 4 weeks; Pb-exposed mice (Pb)-subjected to 14-day Pb (II) nitrate administration at dose 80 mg/kg body weight (b.w.); Pb + Def group-Pb-exposed mice, treated with 20 mg/kg b.w. Def for 2 weeks; and Pb + Sal group-Pb-intoxicated mice, treated with 16 mg/kg b.w. Sal for 14 days. The results demonstrated that Pb exposure significantly increased blood and testicular Pb concentrations, decreased testicular calcium (Ca) content, significantly elevated testicular levels of magnesium (Mg), zinc (Zn), and selenium (Se) but did not significantly affect the endogenous contents of phosphorous (P) and iron (Fe) compared with untreated controls. Pb intoxication induced disorganization of the seminiferous epithelium. Def or Sal administration reduced blood Pb and testicular Pb concentrations in Pb-exposed mice compared with the Pb-intoxicated group. Mg, Zn, and Se concentrations in testes of Pb-exposed mice, treated with Def or Sal, remained higher compared with the untreated controls. Sal significantly increased testicular P concentration compared with untreated controls and significantly elevated the testicular Ca and Fe concentrations compared with the toxic control group. Both chelating agents improved testicular morphology to a great extent. The results demonstrate the potential of both compounds as antidotes for treatment of Pb-induced impairment of male reproductive function.

Low-level developmental lead exposure does not predispose to adult alcohol self-administration, but does increase the risk of relapsing to alcohol seeking in mice: Contrasting role of GLT1 and xCT brain expression

Lead (Pb) is a neurotoxic heavy metal pollutant. Despite the efforts to reduce Pb environmental exposure and to prevent Pb poisoning, exposure in human populations persists. Studies of adults with history of childhood lead exposure have consistently demonstrated cognitive impairments that have been associated with sustained glutamate signaling. Additionally, some clinical studies have also found correlations between Pb exposure and increased proclivity to drug addiction. Thus, here we sought to investigate if developmental Pb exposure can increase propensity to alcohol consumption and relapse using an alcohol self-administration paradigm. Because Pb exposure is associated with increased glutamatergic tone, we also studied the effects on the expression of synaptic and non-synaptic glutamate transporters in brain regions associated with drug addiction such as the nucleus accumbens (NAc), dorsomedial striatum (DMS), dorsolateral striatum (DLS), and medial prefrontal cortex (mPFC). We found that while developmental Pb exposure did not increase risk for alcohol self-administration, it did play a role in relapsing to alcohol. The effects were associated with differential expression of the glutamate transporter 1 (GLT1) and the glutamate/cystine antiporter (xCT). In the NAc and DLS the expression of GLT1 was found to be significantly reduced, while no changes were found in DMS or mPFC. Contrastingly, xCT was found to be upregulated in NAc but downregulated in DLS, with no changes in DMS or mPFC. Our data suggest that lead exposure is involved in relapse to alcohol seeking, an effect that could be associated with downregulation of GLT1 and xCT in the DLS.

Effect of Visnagin on Altered Steroidogenesis and Spermatogenesis, and Testicular Injury Induced by the Heavy Metal Lead

Lead (Pb) is an environmental pollutant causing serious health problems, including impairment of reproduction. Visnagin (VIS) is a furanochromone with promising antioxidant and anti-inflammatory effects; however, its protective efficacy against Pb toxicity has not been investigated. This study evaluated the protective effect of VIS on Pb reproductive toxicity, impaired steroidogenesis and spermatogenesis, oxidative stress and inflammation. Rats received VIS (30 or 60 mg/kg) and 50 mg/kg lead acetate for 3 weeks and blood and testes samples were collected. Pb intoxication impaired the pituitary-testicular axis (PTA) manifested by the decreased serum levels of gonadotropins and testosterone. Pb decreased sperm count, motility and viability, increased sperm abnormalities, and downregulated the steroidogenesis markers StAR, CYP17A1, 3β-HSD and 17β-HSD in the testis of rats. VIS significantly increased serum gonadotropins and testosterone, alleviated sperm parameters and upregulated steroidogenesis. In addition, VIS decreased pro-inflammatory cytokines, testicular lipid peroxidation and DNA fragmentation, downregulated Bax, and enhanced antioxidants and Bcl-2. These results demonstrate the protective effect of VIS against Pb reproductive toxicity in rats. VIS improved serum gonadotropins and testosterone, enhanced steroidogenesis and spermatogenesis, and attenuated oxidative injury, inflammation and apoptosis. Therefore, VIS is a promising candidate for the protection against Pb-induced reproduction impairment.

Integrating active and passive monitoring to assess sublethal effects and mortality from lead poisoning in birds of prey

The ingestion of lead (Pb) ammunition is the most important exposure pathway to this metal in birds and involve negative consequences to their health. We have performed a passive monitoring of Pb poisoning in birds of prey by measuring liver (n = 727) and blood (n = 32) Pb levels in individuals of 16 species found dead or sick in Spain between 2004 and 2020. We also performed an active monitoring by measuring blood Pb levels and biomarkers of haem biosynthesis, phosphorus (P) and calcium (Ca) metabolism, oxidative stress and immune function in individuals (n = 194) of 9 species trapped alive in the field between 2016 and 2017. Passive monitoring results revealed some species with liver Pb levels associated with severe clinical poisoning (>30 μg/g d.w. of Pb): Eurasian griffon vulture (27/257, 10.5%), red kite (1/132, 0.8%), golden eagle (4/38, 10.5%), and Northern goshawk (1/8, 12.5%). The active monitoring results showed that individuals of bearded vulture (1/3, 33.3%), Eurasian griffon vulture (87/118, 73.7%), Spanish imperial eagle (1/6, 16.7%) and red kite (1/18, 5.6%) had abnormal blood Pb levels (>20 μg/dL). Blood Pb levels increased with age, and both monitoring methods showed seasonality in Pb exposure associated with a delayed effect of the hunting season. In Eurasian griffon, blood Pb concentration was associated with lower δ-ALAD activity in blood and P levels in plasma, and with higher blood lipid peroxidation and plasma carotenoid levels in agreement with other experimental and field studies in Pb-exposed birds. The study reveals that Pb poisoning is a significant cause of death and sublethal effects on haem biosynthesis, P metabolism and oxidative stress in birds of prey in Spain.

Protective effects of deferoxamine on lead-induced cardiotoxicity in rats.

Because of the numerous industrial applications of lead (Pb), Pb poisoning is an important public health threat in the world particularly in developing and industrialized countries. Oxidative stress is one of the important mechanisms of Pb-mediated toxicity. Deferoxamine (DFO) is an iron chelating agent that has recently shown antioxidant and antiapoptotic effects. This study investigated the protective capacity of DFO against Pb-induced cardiotoxicity in rats. We used five groups in this study: control, DFO (300 mg/kg), Pb (50 mg/kg), DFO (150 mg/kg) + Pb, DFO (300 mg/kg) + Pb. DFO was administered intraperitoneally 30 min before intraperitoneal injection of Pb for 5 days. After drug treatment, the levels of lactate dehydrogenase (LDH), lipid peroxidation (LPO), glutathione (GSH), and antioxidant enzymes were measured in serum and heart samples. The results showed that pretreatment with DFO reduced Pb-induced oxidative stress markers in serum and cardiac tissues. We found that LDH and LPO levels were significantly increased in Pb-treated rats and decreased with DFO pre-administration. Furthermore, the decreased activities of total antioxidant capacity, and GSH were observed after Pb treatment. However, DFO administration effectively prevented the Pb-induced alterations of these antioxidant enzymes activities. In conclusion, the results presented here indicate that DFO has protective effects in Pb-induced cardiotoxicity in rats, probably due to its antioxidant action and inhibition of oxidative stress.

Pb exposure triggers MAPK-dependent inflammation by activating oxidative stress and miRNA-155 expression in carp head kidney

Lead (Pb) is a toxic heavy metal and an aquatic pollutant. Various amounts of heavy metals are released into the environment through industrial discharge, causing excessive contamination of aquatic ecosystems. The head kidney is a unique immune organ of the bony fish and plays an important role in the metabolism of heavy metals. Studies of toxic Pb exposure that have investigated the head kidney of carp are limited. This study was carried out to explore the potential immunotoxicity effects of Pb and the specific related mechanisms in the carp head kidney. Pb poisoning was shown to induce the production of reactive oxygen species (ROS) and increase the expression levels of phosphorylated proteins related to the MAPK pathway, including p38, extracellular signal-regulated protein kinase (ERK), and c-Jun N-terminal kinase (JNK). We also found that microRNA-155 played a key role in regulating the production of inflammatory factors TNF-α, IL-1β, and IL-6, and the pre-miRNA-155 inhibitor reversed the Pb-induced inflammation. In conclusion, these in vitro and in vivo findings suggest that oxidative stress and the MAPKs are involved in the Pb-induced inflammasome response, and the production of microRNA-155 aggravated the occurrence of inflammation in carp head kidney.

LEAD AND CADMIUM SUBCHRONIC INTOXICATION IN RATS AS A FACTOR OF DAMAGE TO THE CARDIOVASCULAR SYSTEM

Lead-cadmium intoxication is an occupational risk factor for copper-smelting industry workers. People inhabiting the areas near the copper plants are also at risk. Subchronic intoxication was modeled by repeated intraperitoneal injections of lead acetate and cadmium chloride both in isolation and in combination, 3 times a week for 6 weeks. A heart rate decrease in animals with Cd intoxication and a blood flow velocity decrease in those with Pb intoxication have been found. The impact of Pb and Cd on blood pressure proved to be contra-directional. ECG analysis revealed a prolonged duration of QRS in Cd intoxication, a prolonged QT interval and a baseline lowering in Pb+Cd intoxication. A variety of changes has been found with respect to the diameter of cardiomyocytes and the thickness of aortic wall layers in Pb and/or Cd intoxication. Any toxic exposure resulted in the decrease in number of nuclei per unit area of myocardium histological preparation.

Effect of humic acids on lead poisoning in bones and on a subcellular level in mitochondria.

Humic acids (HA) are natural substances which exhibit a remarkable spectrum of health benefits, such as their role in chelation. This study aims to supplement the current knowledge on the chelating effects of HA in chronic lead intoxication in rat femurs and in liver, heart and kidney mitochondria in an experiment lasting 10weeks. Lead acetate trihydrate was administered to rats for 5weeks at a daily dose of 155.5mg/kg body weight. At the same time, rats were given three concentrations of HA, with their effect measured over the following 5weeks. Increased Pb concentrations were detected in the femur after the first week, while HA-administered groups showed a tendency towards inhibiting the increase in Pb deposition. After 5weeks, Pb concentrations dropped significantly in the HA groups. At the same time, however, other elements were redistributed, with a decrease in Se and Zn being particularly noteworthy. While an increase in Pb concentrations was found after 5weeks of Pb administration, a concentration of 1% HA resulted in the least significant increase in Pb as well as an increase/decrease in Se/Cu, respectively. In mitochondria, an increase in Pb content was detected after the first and fifth weeks with concomitant redistribution of other elements. At the end of the experiment, again in the 1% HA group, Pb concentrations remained higher only in the liver with the other elements sufficiently normalized, indicating this concentration to be useful in the treatment of Pb intoxication.

Lactobacillus plantarum LP33 attenuates Pb-induced hepatic injury in rats by reducing oxidative stress and inflammation and promoting Pb excretion

Lead (Pb) is one of the most common heavy metals and is harmful to human health. The liver is considered as a major target organ for Pb poisoning. Although probiotics have been shown to alleviate liver injury, the protective effect of Lactobacillus plantarum LP33 (LP33) against Pb-induced hepatotoxicity remains unclear. In order to explore the hepatoprotective effect of LP33, LP33 was administered to Pb-intoxicated Sprague-Dawley rats once daily by oral gavage for 8 weeks. The present results showed that LP33 supplementation alleviated liver injury, and inhibited oxidative stress and inflammation in Pb-exposed rats. Treatment with LP33 also promoted the phosphorylation of adenosine monophosphate-activated protein kinase and protein kinase B, activated nuclear factor erythroid 2-related factor 2 signaling and inhibited the activation of nuclear factor-κB signaling in liver tissues of rats exposed to Pb. Additionally, LP33 exhibited adequate Pb-binding capacity and satisfactory survival under simulated gastrointestinal conditions in vitro, and promoted Pb excretion via enterohepatic circulation of bile acids. This study demonstrated that LP33 reduced Pb-induced oxidative stress and inflammation and promoted Pb excretion, thereby attenuating the Pb-induced hepatic injury. Our findings suggest that LP33 supplementation may be a potential strategy for the treatment of Pb-induced hepatic toxicity.

Blood lead levels and aberrant DNA methylation of the ALAD and p16 gene promoters in children exposed to environmental-lead

BackgroundLead (Pb) is a well-known toxic heavy metal which can have serious public health hazards. As of today, there is no safe threshold for Pb exposure, especially for children. Lead exposure has been associated with adverse health outcomes involving epigenetic mechanisms, such as aberrant DNA methylation. The objective of the present study was to elucidate the associations between blood lead levels (BLLs) and gene-specific promoter DNA methylation status in environmental Pb-exposed children from Kabwe, Zambia. MethodsA cross-sectional study was conducted using 2 to 10-year-old children from high Pb exposed area (N = 102) and low Pb exposed area (N = 38). We measured BLLs using a LeadCare II analyzer and investigated the methylation status of the ALAD and p16 gene promoters by methylation–specific PCR. ResultsThe mean BLLs were 23.7 μg/dL and 7.9 μg/dL in high Pb exposed and low Pb exposed children, respectively. Pb exposure was correlated with increased methylation of the ALAD and p16 genes. The promoter methylation rates of ALAD and p16 in high Pb exposed children were 84.3% and 67.7%, and 42.1% and 44.7% in low Pb exposed children, respectively. Significantly increased methylation was found in both genes in high Pb exposed children compared with low Pb exposed children (p < 0.05). Children with methylated ALAD and p16 genes showed an increased risk of Pb poisoning (odd ratio >1) compared to the unmethylated status. ConclusionsThis study for the first time tries to correlate promoter methylation status of the ALAD and p16 genes in environmental Pb-exposed children from Kabwe, Zambia as a representative. The result suggests that Pb exposure increases aberrations in ALAD and p16 gene methylation, which may be involved in the mechanism of Pb toxicity.