Ameliorating Effect of Apium graveolens (Celery) Extracts on IL-6 Plasma Level and Expression of Caspase 3 on Liver in Animal Model of Lead Intoxication.

<b>Background and Objective:</b> Lead poisoning (Pb) is a big problem because it is found in almost all objects in daily life such as vehicle fuel, water pipes, ceramics, cosmetics and others. Continuous lead exposure can increase ROS resulting in an increase in hepatic IL-6 and caspase 3 which replaces hepatic cell apoptosis. The objective of this study was to determine the effect of <i>Apium graveolens</i> (celery) extract on plasma IL-6 and hepatic caspase 3 levels. <b>Materials and Methods:</b> This study used a post-test control group design. The research subjects were 20 Wistar rats that met the inclusion criteria and were divided into 4 groups randomly, namely (a) Sham group that had no treatment, (b) Negative control group was induced with lead acetate 200 mg kg¹ body weight/day without any treatment (c) Positive control group and (d) Treated group. On the 15th day, blood was taken to check IL-6 levels and tissue was taken for liver caspase 3 examination by immunohistochemical method. Data analysis used the one-way ANOVA test and continued with the <i>post hoc</i> LSD test. <b>Results:</b> The highest mean caspase 3 expression was in the control group 45.84±4.39 pg mL¹, while the mean of IL-6 plasma level was highest in the P1 641.33±39.72 pg mL¹ group. The Mann-Whitney test showed a significant difference in IL-6 levels between the study groups (p = 0.000). The Mann-Whitney test showed a significant difference in caspase 3 levels between the study groups (p = 0.000). <b>Conclusion:</b> Giving celery extract 300 mg kg¹ body weight/day affects plasma IL-6 and hepatic caspase 3 levels in lead acetate-induced rats.

Influence of lead-induced toxicity on the inflammatory cytokines.

Lead (Pb2+) is a hazardous heavy metal that is pervasive in the human environment as a result of anthropogenic activity, and poses serious health risks, particularly in children. Due to its innumerable unique physical and chemical properties, it has various applications; therefore, it has become a common environmental pollutant. Lead may cause oxidative stress, and accumulating evidence indicates that oxidative stress influences the pathophysiology of lead poisoning, also called plumbism. The immune system is continually exposed to various environmental pathogens and xenobiotics, including heavy metals such as lead, and appears to be one of the most vulnerable targets. After being exposed to lead, cells are subjected to oxidative stress as a result of reactive oxygen species (ROS) production. When the generation and consumption of ROS are out of equilibrium, various cell structures, particularly phospholipids are disrupted leading to lipid peroxidation. Various inflammatory signalling pathways are activated as a consequence, along with reduced disease resistance, inflammation, autoimmunity, sensitization and disruption of the cell-mediated and humoral immune systems. Lead negatively affects the metabolism of cytokines, including the interleukins IL-2, IL-1b, IL-6, IL-4, IL-8, tumor necrosis factor-alpha (TNF-α), and interferon-gamma (IFN), as well as the expression and functioning of inflammatory enzymes such as cyclooxygenases. However, the cause of toxicity depends on the kind of lead, dosage, route of entry, exposure period, age, host and genetic predisposition.

Increased MCHC*RDW-SD interaction values: indicators of neurological impairment in lead-poisoned children.

Background: The neurotoxic effects of lead in children can have long-lasting and profound impacts on the developing nervous system. This study aimed to identify a reliable and easily accessible biomarker to monitor neurological impairment in lead-poisoned children. Methods: We analyzed hematological data from 356 lead-poisoned children, comparing them with age and gender-matched healthy controls. Multivariate logistic regression and receiver operating characteristic (ROC) analysis were employed to identify and evaluate potential biomarkers for neurological damage. Results: Significant changes in erythrocyte parameters were observed in lead-poisoned children. Upon further analysis, increased mean corpuscular hemoglobin concentration (MCHC) and red cell distribution width-standard deviation (RDW-SD) interaction values were found to be significantly associated with neurological impairment. The MCHC*RDW-SD interaction model demonstrated an AUC of 0.76, indicating its effectiveness in reflecting neurological damage. Additionally, the MCHC*RDW-SD Interaction value showed weak or no correlation with other erythrocyte parameters, suggesting its independence as an indicator. Conclusion: Our findings propose the increased MCHC*RDW-SD interaction value as a robust and independent biomarker for detecting neurological impairment in lead-poisoned children. This underscores the potential of utilizing specific erythrocyte parameters for screening the neurotoxic effects of lead exposure in pediatric populations.

Lead exposure in Chinese children: Urbanization lowers children's blood lead levels (BLLs).

Lead is a toxic metal that can pose a huge threat to children's health. China has experienced rapid urbanization since the reform in 1978; however, there has been no examination of the potential influence of this urbanization on children's blood lead levels (BLLs). This study is the initial investigation to explore the correlation between urbanization and BLLs in Chinese children. Five windows of time are considered: pre-2000, 2001-2005, 2006-2010, 2011-2015 and 2016-2021. The results show that urbanization affected lead distribution in urban soil and agricultural soil during the above periods, especially in northern China. The higher non-carcinogenic risk of lead for children is consistent with the lead pollution in soil (3 < Igeo ≤ 4). Urban children's BLLs are slightly higher than those of rural children in 2001-2010, but rural children's BLLs in 2011-2021 are higher than those of urban children during China's urbanization. The areas of rural decline and the areas of urban growth increased across all the window periods. However, the BLLs decrease in all rural and urban areas during all window periods, especially in urban areas. Children's BLLs have a significantly negative correlation with urban areas (p < 0.01). Therefore, China's urbanization has a significant effect on the decrease in children's BLLs. The significance of this study is to provide a fresh perspective and innovative strategy for policymaking in order to reduce children's BLLs and prevent lead exposure. This can be achieved by transforming their external living environment from a rural lifestyle to an urban one, while also ensuring access to well education and maintaining a balanced nutrient intake.

Outbreak of lead poisoning from a civilian indoor firing range in the UK.

INTRODUCTION: Lead exposure from discharged lead dust is a recognised risk at firing ranges. We report a lead poisoning outbreak among staff and their close contacts at a UK civilian indoor 24 m firing range. METHODS: A retrospective review was undertaken of data collected on all patients at risk of lead poisoning identified either by direct referral to the Clinical Toxicology clinicians at the West Midlands Poisons Unit, or via the Trace Elements Supra-Regional Assay Service Laboratory at Sandwell hospital. RESULTS: Eighty-seven patients were identified as having possible lead exposure, either at the firing range or via close contacts. Of these, 63 patients aged between 6 months and 78 years attended for blood lead concentration (BLC) testing. The highest BLC at presentation was 11.7 µmol/L (242 µg/dL). Only nine patients reported any symptoms at presentation. Fifteen patients received lead chelation therapy with oral dimercaptosuccinic acid (or succimer) 30 mg/kg/day or intravenous sodium calcium edetate (EDTA) 75 mg/kg/day, dependent on stock availability. DISCUSSION: This report highlights the need for vigilance of lead poisoning as an occupational hazard in the UK, including at recreational facilities such as indoor firing ranges. It emphasises the importance of regulation of lead exposure in the workplace, particularly given the vague symptoms of lead poisoning, and proposes re-appraisal of UK legislation. This report also highlights potential issues surrounding stock availability of rarely used antidotes for uncommon presentations in the event of an outbreak of poisoning.

Integral trends in research of lead exposure and child health from 2012 to 2022: a bibliometric analysis.

Lead poisoning in children is a non-negligible and ongoing threat to children's health and optimal development worldwide. There is no sufficient scientometric analysis available on this subject, though. Aiming to uncover the research development, hotspots, and possible future orientation, we performed a scientometric analysis of related publications from 2012 to 2022. Initial information was accessed using the "Analysis Results" and "Create Citation Report" sections of the Web of Science core collection database, which were utilized to find original publications in this field of research. Biblioshiny and VOSviewer software were applied to further analyze and visualize the data. The research addressed a range of topics, including yearly publications, highly cited articles, co-cited references, journals, authors, nations, organizations, and keywords. A total of 883 articles were retrieved. From 2018 to 2021, the annual publication output was abundant and peaked in 2019. Among 111 countries, the USA obtained the highest number of documents issued, total citations, and total link strength. Meanwhile, most of the top 15 institutions, including the top four, are located in the USA. Further, we spotted greater scopes with development potential, including enhancing records to lessen exposure to harmful risks, improving methods for observing lead sources, and elucidating the gradient link between lead poisoning symptoms and concentrations. We anticipate that our research will assist researchers in summarizing previous research and providing perspectives for workable prospective study topics.

Who tests for lead and why? A 10-year analysis of blood lead screening, follow-up and CNS outcomes in a statewide US healthcare system.

OBJECTIVES: This study aims to determine (1) which providers in US healthcare systems order lead tests, why and at what frequency and (2) whether current patient population lead levels are predictive of clinical outcomes. METHODS: Retrospective medical record study of all blood lead tests in the Medical University of South Carolina healthcare system 2012-2016 and consequent evidence of central nervous system (CNS)-related disease across a potential 10-year window (2012-2022). RESULTS: Across 4 years, 9726 lead tests resulted for 7181 patients (49.0% female; 0-94 years), representing 0.2% of the hospital population. Most tests were for young (76.6%≤age 3) and non-Hispanic black (47.2%) and Hispanic (26.7%) patients. A wide variety of providers ordered tests; however, most were ordered by paediatrics, psychiatry, internal medicine and neurology. Lead levels ranged from ≤2.0 µg/dL (80.8%) to ≥10 µg/dL (0.8%; max 36 µg/dL). 201 children (3.1%) had initial lead levels over the reference value for case management at the time (5.0 µg/dL). Many high level children did not receive follow-up testing in the system (36.3%) and those that did often failed to see levels fall below 5.0 µg/dL (80.1%). Non-Hispanic black and Hispanic patients were more likely to see lead levels stay high or go up over time. Over follow-up, children with high lead levels were more likely to receive new attention-deficit/hyperactivity disorder and conduct disorder diagnoses and new psychiatric medications. No significant associations were found between lead test results and new CNS diagnoses or medications among adults. CONCLUSIONS: Hospital lead testing covers a small portion of patients but includes a wide range of ages, presentations and provider specialities. Lack of lead decline among many paediatric patients suggests there is room to improve provider guidance around when to test and follow-up.

Difference in concentration of lead (Pb) in meat from pheasants killed using lead and iron (Fe) shotgun ammunition.

The use of lead shotgun ammunition for hunting has been banned in a few jurisdictions and habitats, principally to protect wild birds from poisoning by ingestion of spent lead shot. The EU and UK REACH processes have recently considered bans on lead ammunition throughout the European Union and United Kingdom, including assessments of possible health benefits from reduced human dietary exposure to lead from game meat. Comparisons of the mean lead concentrations in meat from gamebirds killed using lead and non­lead shotgun ammunition have not been published. We compared lead concentrations in meat from wild-shot pheasants from which lead shotgun pellets were recovered (n = 27) with those from which iron pellets were recovered (n = 20), having removed all pellets from the meat before analysis. The mean concentration of lead in meat from pheasants killed using lead shot was 2.10 mg/kg w.w., which is >20 times the European Union's maximum permitted level for the lead concentration in meat from domesticated animals. For pheasants killed using iron shot the mean was 0.07 mg/kg w.w., which is below the maximum permitted level.

Clinical case analysis of 32 children aged 0-6 years with lead poisoning in Nanning, China.

Lead is one of the heavy metals that is toxic and widely distributed in the environment, and children are more sensitive to the toxic effects of lead because the blood-brain barrier and immune system are not yet well developed. The objective of the study was to investigate the clinical characteristics of lead poisoning in children aged 0∼6 years in a hospital in Guangxi, and to provide scientific basis for the prevention and treatment of lead poisoning. We collected and analyzed the clinical data of 32 children with lead poisoning admitted to a hospital in Guangxi from 2010 to 2018. The results showed that most of the 32 cases presented with hyperactivity, irritability, poor appetite, abdominal pain, diarrhea, or constipation. The hemoglobin (HGB), mean corpusular volume (MCV), mean corpuscular hemoglobin (MCH), and hematocrit (HCT) of the lead-poisoned children were all decreased to different degrees and were below normal acceptable levels. Urinary ß2-microglobulin was increased. Blood lead levels (BLL) decreased significantly after intravenous injection of the lead chelator, calcium disodium edetate (CaNa2-EDTA). In addition, HGB returned to normal levels, while MCV, MCH, and HCT increased but remained below normal levels. Urinary ß2-microglobulin was reduced to normal levels. Therefore, in this cohort of children, the high-risk factors for lead poisoning are mainly Chinese medicines, such as baby powder. In conclusion, lead poisoning caused neurological damage and behavioral changes in children and decreased erythrocyte parameters, leading to digestive symptoms and renal impairment, which can be attenuated by CaNa2-EDTA treatment.

A Case of Severe Lead Encephalopathy with Cardiac Arrest Managed During a Chelation Shortage.

INTRODUCTION: For many years, the standard of care in the USA has been to treat acute lead encephalopathy with a combination parenteral dimercaprol (BAL) and CaNa2EDTA. We present a case of a pediatric patient with severe lead encephalopathy, complicated by cardiac arrest, who was treated with an alternative regimen when CaNa2EDTA was unavailable. CASE REPORT: A 24-month-old male was brought by ambulance to an emergency department (ED) with new onset seizures and sustained a cardiac arrest. An initial blood lead concentration returned at 263 mcg/dl. The hospital was unable to obtain CaNa2EDTA due to the nationwide shortage. For this reason, the patient was chelated with BAL IM for 12 days and dimercaptosuccinic acid (DMSA) for 28 days. He received a second 5-day course of BAL due to rebounding blood lead concentrations. Eight days after cardiac arrest, he was extubated; however, despite ongoing therapy, subsequent follow-up 2 months later demonstrated persistent cognitive deficits. DISCUSSION: The combination of DMSA and BAL was effective in rapidly decreasing whole blood lead concentrations. Drug shortages continue to have implications for the management of poisoned patients. This case highlights how shortages of chelating agents complicate patient care.

Secular trends in blood lead concentrations of school-age children in Montevideo, Uruguay from 2009 to 2019.

Lead exposure continues to be a public health problem globally, yet very few countries perform systematic biomonitoring or surveillance of children's blood lead levels (BLLs). Secular trends in children's BLLs have not been well characterized outside North America and Europe. In 2009-19, we conducted a series of non-representative cross-sectional surveys in Montevideo, Uruguay, enrolling children living in areas of the city with known or suspected lead contamination. Lead was measured with atomic absorption spectrometry on fasting venous blood samples. Of the 856 children representing independent (non-sibling) observations, 759 had BLL measures. Other missing data were imputed. Using linear and logistic regression models, we estimated the covariate-adjusted year to year difference in mean BLL and the likelihood of having BLL ≥5 and BLL ≥3.5 µg/dL. At the start of the study, mean ± SD BLL was 4.8 ± 2.6 µg/dL, and at the end 1.4 ± 1.4 µg/dL. The prevalence of BLL ≥5 and BLL ≥3.5 µg/dL also differed markedly between 2009 and 2019 (30.8% vs. 2.7% and 53.8% vs. 5.8%). Similarly, where 80.8% of children had BLL ≥2 µg/dL in 2011, in 2019 that number was 19.3%. The estimated year to year difference in BLL was ∼0.3 µg/dL. Despite this progress, pediatric lead exposure remains a problem in Montevideo. In years 2015-19, between 19 and 48% of school children had BLL ≥2 µg/dL, a level at which adverse neurobehavioral outcomes continue to be reported in the literature. Continued prevention and risk-reduction efforts are needed in Montevideo, including systematic surveillance of BLLs in all children.

Sub-lethal impacts of lead poisoning on blood biochemistry, immune function and delta-aminolevulinic acid dehydratase (δ-ALAD) activity in Cape (Gyps coprotheres) and white-backed (G. africanus) Vulture chicks.

Although the prevalence of lead poisoning in southern Africa's Gyps vultures is now well-established, its finer physiological effects on these endangered species remain poorly characterised. We evaluated the sub-lethal impact of acute lead exposure on Cape and White-backed Vulture chicks from two breeding colonies in South Africa, by analysing its possible effects on key blood biochemistry parameters, immune function, packed cell volume and δ-aminolevulinic acid dehydratase (δ-ALAD) activity. All 37 White-backed Vulture nestlings sampled displayed elevated lead levels (>10 µg/dL), and seven had blood [Pb] >100 µg/dL. Eight of 28 Cape Vulture nestlings sampled had blood [Pb] exceeding background exposure, with one showing blood [Pb] >100 µg/dL. Delta-aminolevulinic acid dehydratase (δ-ALAD) activity was significantly and negatively related to blood [Pb] in nestlings from both species, with 50% inhibition of the enzyme predicted to occur at blood [Pb] = 52.8 µg/dL (White-backed Vulture) and 18.8 µg/dL (Cape Vulture). Although no significant relationship was found between % packed cell volume (PCV) and blood [Pb], the relatively lower mean PCV of 32.9% in White-backed Vulture chicks, combined with normal serum protein values, is likely indicative of depression or haemolytic anaemia. The leukogram was consistent in both species, although the presence of immature heterophils suggested an inflammatory response in White-backed Vulture chicks with blood [Pb] >100 µg/dL. Values for cholesterol, triglycerides, total serum protein, albumin, globulin, albumin/globulin ratio, alanine aminotransferase (ALT) and gamma-glutamyl transferase (GGT) were consistent with values previously reported. Calcium and phosphorus concentrations suggested no adverse effects on bone metabolism. A significant decrease in urea: uric acid (U:UA) ratio at blood [Pb] >100 µg/dL in White-backed Vulture chicks, brought about by a decrease in urea production, raises the possibility of hepatic abnormality. These results suggest that δ-ALAD activity may serve as a sensitive biomarker of lead toxicity in both species, while highlighting the need to better understand the significant variability in sensitivity that is observed, even between closely related members of the same genus.

Gastrointestinal Manifestations of Lead Poisoning: A Brief Report.

Gastrointestinal (GI) manifestations of lead poisoning include abdominal pain, constipation, and diarrhea. Depending on the severity of a symptom, surgical consultation is required. The present study aimed to make a comparison between the mean blood lead levels of patients hospitalized for lead toxicity and the various Gl symptoms. A retrospective cross-sectional study was performed in 2020 at Khorshid Hospital, the main regional referral center for poisoned patients (Isfahan, Iran). A total of 82 patients aged ≥18 years who were hospitalized for lead poisoning during 2017-2018 were included in the study. Patients' information was extracted from hospital medical records, including demographic information, clinical manifestations, blood lead levels, and treatment outcome. The mean age of the patients was 48.18±11.9 years, 91.5% were men, and 62.2% suffered from multiple GI symptoms, with abdominal pain being predominant (31.7%). Blood lead levels in patients with multiple GI symptoms were higher than those with only one symptom (P=0.01). Surgical consultation was required in 14.6% of the patients. Multiple GI symptoms were the main predictive factor for blood lead levels above 70 mg/dL (P=0.03, Odds ratio=3.06, 95% CI=1.09-8.61). Given the prevalence of abdominal pain and its association with elevated blood lead levels, differential diagnosis of abdominal pain should include lead toxicity.

Unmasking herbal medication-induced lead poisoning in a geriatric patient with gastrointestinal symptoms.

Lead poisoning, often associated with occupational exposure, can also arise from intake of traditional and herbal medicines with high lead content. Geriatric patients displaying gastrointestinal symptoms from such sources are frequently misdiagnosed. An individual in his 70s reported to our geriatric clinic with vomiting, constipation and anaemia. A meticulous history unveiled his recent intake of herbal remedies. Heavy metal assay indicated elevated lead levels in his blood and urine, consistent with the high lead content we measured in the herbal medication. Following supportive treatment, nutritional supplementation and chelation therapy with calcium disodium EDTA, he improved. Follow-up tests indicated a decrease in lead levels and resolution of anaemia. This case emphasises the importance of considering lead poisoning as a potential diagnosis in patients with unexplained symptoms, particularly when there is a history of herbal or alternative medication intake. Timely recognition and appropriate management can lead to better outcome.

Inflammatory low back pain with radiculopathy revealing epidural disintegration of a bullet complicated by lead poisoning.

Inflammatory low back pain with radiculopathy is suggestive of cancer, infection or inflammatory diseases. We report a unique case of a 42-year-old patient with an acute inflammatory low back pain with bilateral radiculopathy associated with weight loss and abdominal pain, revealing the disintegration of a lead bullet along the epidural space and the S1 nerve root complicated by lead poisoning. Because of the high blood lead level of intoxication (>10 times over the usual lead levels) and the failure of repeated lead chelator cycles, a surgical treatment to remove bullet fragments was performed. It resulted in a significant decrease of pain and lead intoxication.

Lead poisoning: Clinical and laboratory considerations.

Lead has been a known source of toxicity for millennia due to widespread use until the 20th century. Consequently, there remains significant, though decreasing, exposure to lead throughout the world. Clinical signs and symptoms of lead toxicity are well-documented but is particularly concerning for children six years of age and under, as brain development is rapid and therefore, is likely to be affected by even low levels of lead. Therefore, in the United States, it is recommended that young children to be routinely screened for blood lead levels. Blood lead levels can be measured by various methods in laboratories with blood collection greatly impacting possible lead contamination of samples. The history, presentation, and laboratory testing methodologies will be discussed.