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.

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.

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.

Cryptogenic Abdominal Pain: Recognizing False Leads.

BACKGROUND Lead toxicity is a rare yet serious condition which can be difficult to diagnose due to vague presenting symptoms. Other pathologies can also mimic the symptoms of chronic lead toxicity, making an already difficult diagnosis more challenging. There are multiple environmental and occupational contributors to lead toxicity. A thorough history and an open differential is the key to diagnosing and treating this rare disease. With increasing diversity of our patient population, we should keep an open differential, as the epidemiological features of presenting concerns have diversified as well. CASE REPORT A 47-year-old woman presented with persistent nonspecific abdominal pain despite extensive prior work, surgeries and a prior diagnosis of porphyria. This patient was eventually diagnosed as having lead toxicity when her most recent work-up for abdominal pain revealed no urine porphobilinogen and a high lead level. The cause of lead toxicity was attributed to be an eye cosmetic called "Surma", which can have variable lead levels. Chelation therapy was advised for the patient. CONCLUSIONS It is important to recognize the difficulty in this challenging diagnosis for nonspecific abdominal pain and to eliminate the mimickers. This case is interesting because the patient was initially diagnosed with porphyria, highlighting how heavy metals, lead in this case, can lead to a false-positive diagnosis of porphyria. Accurate diagnosis requires awareness of the role of urine porphobilinogen, checking lead levels, and an open differential. This case also emphasizes the importance of avoiding anchor bias to make a timely diagnosis of lead toxicity.

Lead poisoning in a 6-month-old infant: a case report.

Background: Lead is a toxic element of the environment that leads to major complications once it enters the blood stream, affecting multiple organs and systems of the body. Methods: We present a case of a 6-month-old female infant diagnosed with lead poisoning after presenting for routine child health care. The child's mother denied that the infant had a history of exposure to lead-containing substances. After a month of calcium supplementation, the patient's blood lead level remained elevated. We then tested the blood lead level of the mother and father. The results showed that the blood lead level of the mother was 77.0 µg/L and that of the father was 36.9 µg/L. The high blood lead level of the mother attracted our attention. We found that the mother had been using an external traditional Chinese medicine, Hu Wang Fen, which contains lead. After the mother's discontinuation of use of the traditional medicine, the child was treated with symptomatic treatment and chelation therapy. Subsequently, the patient's blood lead level decreased significantly. Results: Lead toxicity can be a life-threatening problem because of its potential for severe complications. In children, there is no safe blood lead level, and the toxic effects of lead can be prevented by the awareness and avoidance of traditional Chinese medicines that may contain lead. Conclusion: Even though the diagnosis of lead poisoning remains difficult in children, it must be taken into consideration by the clinician when treating a child using traditional Chinese medicines.

Lead toxicity and potential therapeutic effect of plant-derived polyphenols.

BACKGROUND: Due to its unique physical and chemical properties, lead is still used worldwide in several applications, especially in industry. Both environmental and industrial lead exposures remain a public health problem in many developing and rapidly industrializing countries. Plant polyphenols are pleiotropic in their function and have historically made a major contribution to pharmacotherapy. PURPOSE: To summarize available pre-clinical and limited clinical evidence on plant polyphenols as potential antidotes against lead poisoning and discuss toxic mechanisms of lead. METHOD: A comprehensive search of peer-reviewed publications was performed from core collections of electronic databases such as PubMed, Web of Science, Google Scholar, and Science Direct. Articles written in English-language from inception until December 2022 were selected. RESULTS: In this review, we review key toxic mechanisms of lead and its pathological effects on the neurological, reproductive, renal, cardiovascular, hematological, and hepatic systems. We focus on plant polyphenols against lead toxicity and involved mechanisms. Finally, we address scientific gaps and challenges associated with translating these promising preclinical discoveries into effective clinical therapies. CONCLUSION: While preclinical evidence suggests that plant polyphenols exhibit bioprotective effects against lead toxicity, scant and equivocal clinical data highlight a need for clinical trials with those polyphenols.

Biomimetic Antidote Nanoparticles: a Novel Strategy for Chronic Heavy Metal Poisoning.

Chronic lead poisoning has become a major factor in global public health. Chelation therapy is usually used to manage lead poisoning. Dimercaptosuccinic acid (DMSA) is a widely used heavy metal chelation agent. However, DMSA has the characteristics of poor water solubility, low oral bioavailability, and short half-life, which limit its clinical application. Herein, a long-cycle slow-release nanodrug delivery system was constructed. We successfully coated the red blood cell membrane (RBCM) onto the surface of dimercaptosuccinic acid polylactic acid glycolic acid copolymer (PLGA) nanoparticles (RBCM-DMSA-NPs), which have a long cycle and detoxification capabilities. The NPs were characterized and observed by particle size meters and transmission electron microscopy. The results showed that the particle size of RBCM-DMSA-NPs was approximately 146.66 ± 2.41 nm, and the zeta potential was - 15.34 ± 1.60 mV. The homogeneous spherical shape and clear core-shell structure of the bionic nanoparticles were observed by transmission electron microscopy. In the animal tests, the area under the administration time curve of RBCM-DMSA-NPs was 156.52 ± 2.63 (mg/L·h), which was 5.21-fold and 2.36-fold that of free DMSA and DMSA-NPs, respectively. Furthermore, the median survival of the RBCM-DMSA-NP treatment group (47 days) was 3.61-fold, 1.32-fold, and 1.16-fold for the lead poisoning group, free DMSA, and DMSA-NP groups, respectively. The RBCM-DMSA-NP treatment significantly extended the cycle time of the drug in the body and improved the survival rate of mice with chronic lead poisoning. Histological analyses showed that RBCM-DMSA-NPs did not cause significant systemic toxicity. These results indicated that RBCM-DMSA-NPs could be a potential candidate for long-term chronic lead exposure treatment.

Lead poisoning with encephalic and neuropathic involvement in a child: case report.

Lead is a toxic substance in our environment that affects adults and children of all socioeconomic backgrounds, lead poisoning is one of the most common exposures that can cause inter alia significant neurological and functional damage in humans. Children are particularly vulnerable because of the effects of the toxicity on their developing nervous systems with potentially irreversible consequences. We report a case of severe lead poisoning encephalo-neuropathy in a 3-year-old girl, admitted for progressive paraplegia, swallowing disorders, and aphasia. A multitude of investigations undertaken could not explain her atypic symptoms, so anamnesis was redone in the sense of a toxic origin, we found a notion of pica, and a traditional herbalist father, so probably consumption of medications based on traditional medicine products. A venous blood lead level (BLL) was extremely elevated at 176.4 µg/l. The child was treated with an oral chelator succimer (SUCCICAPTAL). During the two following months in the intensive care unit, the child showed progressive respiratory distress and worsening signs of the nervous system. Despite treatment and the use of lead chelators, the patient died due to septic shock. Lead is highly toxic even at very low exposure levels, at high levels of exposure, it can damage the reproductive organs, immune system, liver and kidneys. in children, it can affect neurocognitive and behavioral development that could be irreversible. Peripheral and central nervous system damage should be considered as a possible manifestation of lead poisoning.

Non-occupational lead poisoning associated with traditional Chinese medicine: A case report.

Introduction: Traditional Chinese medicine has a long history and is widely popular in China because of its safety and small side effects. In Chinese families, people believe that the combination of traditional Chinese and Western medicine is more effective, and in terms of conditioning and health care, they tend to rely on traditional Chinese medicine. However, the toxic and side effects of traditional Chinese medicine, especially heavy metal poisoning, should not be ignored. Patient concerns: A case of non-occupational lead poisoning caused by long-term use of traditional Chinese medicine. Diagnosis: A 21-year-old man with severe colic periumbilical pain was referred to our hospital. Through careful inquiry of his medical history, we found that he had been taking traditional Chinese medicine to treat facial acne in the past year. His test results showed anemia, liver damage, blood lead concentration of 1,268.4 µg/L, and bone marrow smear showed basophilic stippling erythrocyte. The patient was diagnosed with "lead poisoning." Interventions: The patient was given treatment with lead driving. Outcomes: The patient recovered after treatment. Conclusion: We found that lead poisoning in patients taking traditional Chinese medicine has been reported from time to time. Through consulting the data, we summarized the most common drugs leading to lead poisoning, and reviewed the pathogenesis and common clinical manifestations of lead poisoning. Because lead poisoning is easy to be misdiagnosed, we should ask more carefully about the past history and drug history of patients in order to make timely diagnosis and treatment.

Method to assess the potential magnitude of terrestrial European avian population reductions from ingestion of lead ammunition.

Current estimates of terrestrial bird losses across Europe from ingestion of lead ammunition are based on uncertain or generic assumptions. A method is needed to develop defensible European-specific estimates compatible with available data that does not require long-term field studies. We propose a 2-step method using carcass data and population models. The method estimates percentage of deaths diagnosed as directly caused by lead poisoning as a lower bound and, as an upper bound, the percentage of possible deaths from sublethal lead poisoning that weakens birds, making them susceptible to death by other causes. We use these estimates to modify known population-level annual mortality. Our method also allows for potential reductions in reproduction from lead shot ingestion because reductions in survival and reproduction are entered into population models of species with life histories representative of the most groups of susceptible species. The models estimate the sustainability and potential population decreases from lead poisoning in Europe. Using the best available data, we demonstrate the method on two taxonomic groups of birds: gallinaceous birds and diurnal raptors. The direction of the population trends affects the estimate, and we incorporated such trends into the method. Our midpoint estimates of the reduction in population size of the European gallinaceous bird (< 2%) group and raptor group (2.9-7.7%) depend on the species life history, maximum growth rate, population trend, and if reproduction is assumed to be reduced. Our estimates can be refined as more information becomes available in countries with data gaps. We advocate use of this method to improve upon or supplement approaches currently being used. As we demonstrate, the method also can be applied to individual species of concern if enough data across countries are available.

Essential Trace Metals as Countermeasure for Lead Toxicity.

Lead (Pb) is the most common toxic heavy metal that is physiologically non-essential and imposes health complications in animals and humans. Chelation therapy is considered as the definite therapy for acute lead toxicity; clinical uses of chelating agents are not recommended in long-term lead toxicity and in children. Research reveals that essential trace metals can counteract empirical Pb toxicity. This article collates the prototypical evidence of the preventive action of essential trace metals towards Pb toxicity in animals. Zinc, selenium, and their combinations are effective here. The key mechanisms of homeostasis of essential metals and cytoprotection are: modulation of signal transduction pathways of apoptosis, inflammation and immune functions (for selenium), attenuation of oxidative stress by augmenting non-enzymatic and enzymatic antioxidative systems and interference in lead accumulation in the body. By means of these mechanisms, these essential trace metals may counteract long-term lead toxicity for susceptible subjects. These mineral nutritional supplementation can easily be employed with no or less adverse effects compared to the typical chelation treatment.

Lead poisoning among asymptomatic individuals with a long-term history of opiate use in Golestan Cohort Study.

BACKGROUND: Recent reports of lead poisoning suggest that people who use opium may be exposed to high amounts of lead. Here, we investigate the association between opium use and blood lead levels (BLL) in a population-based cohort study. METHODS: In 2017, we studied a random sample of 410 people who currently (both within the past year and the past month) used opium and 104 who did not from participants of the Golestan Cohort Study in northeast Iran. Participants were stratified by sex and tobacco use history, completed a comprehensive opiate and tobacco use questionnaire and provided blood. BLL was measured by Lead Care® II Blood Lead Test Kit, validated by inductively coupled plasma triple quadrupole mass spectrometry. BLL was categorized as "<5 µg/dL", "elevated" (5-10 µg/dL), "high" (10-50 µg/dL), and "very high" (above 50 µg/dL). To assess the association between BLL categories and opiate use, route of consumption and weekly use, we used ordered logistic regression models, and report OR (odds ratio) and 95% CI (confidence interval) adjusted for age, sex, place of residence, education, occupation, household fuel type, and tobacco use. RESULTS: In the cohort, participants used only raw (teriak) or refined (shireh) opium, which were smoked (45%, n = 184), taken orally (46%, n = 189), or both (9%, n = 37), for a mean duration of 24.2 (standard deviation: 11.6) years. The median BLL was significantly higher in people who currently used opium (11.4 µg/dL; IQR: 5.2-23.4) compared with those who did not (2.3 µg/dL; IQR: 2.3-4.2), and the highest median BLL was seen in oral use (21.7 µg/dL; IQR: 12.1-34.1). The BLL was <5 µg/dL among 79.8% of people with no opiate use, compared with only 22.7% in those using opium. BLL was elevated in 21.7%, high in 50.5% and very high in 5.1% of people using opium. About 95% of those with oral (180/189) or dual use (35/37) and 55% (102/184) of those who smoked opium had levels of blood lead above 5 µg/dL. The OR for the association between any opium use and each unit of increase in BLL category was 10.5 (95%CI: 5.8-19.1), and oral use of opium was a very strong predictor of increasing BLL category (OR=74.1; 95%CI: 35.1-156.3). This odds ratio was 38.8 (95%CI: 15.9-95.1) for dual use and 4.9 (95%CI: 2.6-9.1) for opium smoking. There was an independent dose-response association between average weekly dose and BLL among people using opium, overall and when stratified by route of use. CONCLUSION: Our results indicate that regular use of lead-adulterated opium can expose individuals to high levels of lead, which may contribute to mortality and cancer risks associated with long-term opium use.

[Severe lead poisoning caused by ayurvedic medicine]. / Schwere Bleivergiftung durch ayurvedisches Heilmittel.

HISTORY: We report the case of a young patient who presented to our emergency department with reduced general condition, anemia, and crampy abdominal pain. A previous inpatient workup including abdominal imaging and bone marrow aspiration had not yielded a diagnosis. On inquiry, the patient reported oral ingestion of an Ayurvedic remedy over the course of one month. FINDINGS: 24-year-old circulatory stable patient in reduced general condition with gray skin coloration and a dark gingival margin. Laboratory testing revealed an increase in transaminases and normocytic anemia. A peripheral blood smear showed basophilic stippling of the erythrocytes. Significantly elevated lead levels were detected in the patient's blood and hair. Toxic lead levels were detected in the ingested preparation. DIAGNOSIS: Severe lead poisoning caused by self-medication with an Ayurvedic remedy. Analysis revealed a daily oral lead load of 136 times the maximum permissible dose. THERAPY AND COURSE: By means of chelation therapy, the blood lead levels were significantly reduced, and there was a complete regression of the complaints as well as a normalization of the laboratory findings. CONCLUSION: Lead has toxic effects on all organ systems of the body and is stored in the bone for decades. Symptoms of poisoning are nonspecific; a thorough history and generous indication for measuring lead levels are helpful for the diagnosis.

Abdominal pain caused by lead toxicity due to over the counter herbal medicines: A case series.

In the last three decades, the use of herbal medications has been increasing for the treatment of various chronic disorders. Studies in the past have shown that many of these medicines could contain high levels of heavy metals, including lead. Therefore, we planned this study to evaluate the possibility of lead toxicity as the underlying cause in patients consuming these unnamed herbal medicines among patients presenting with significant abdominal pain. (Unexplained abdominal pain means pain in abdomen in which no etiology could be ascertained after all possible routine and specialized investigations including computerized axial tomography [CT] of the abdomen and upper gastrointestinal [UGI] endoscopy/colonoscopy). This is an observational case series of prospectively maintained data of all patients having unexplained abdominal pain and found to have an elevated blood lead level from 2011 to 2019. Lead toxicity was diagnosed when its blood lead level was >25 µg/dL. Total sixty-six patients with unexplained abdominal pain from 2011 to 2019 were recruited. Out of the sixty-six patients, seventeen had elevated blood lead levels. All seventeen patients had a history of ingestion of herbal medicines for more than 6 months. Among the seventeen patients, eight were taking it for infertility and sexual dysfunction, six for diabetes, two for arthritis and one for hypertension. Basophilic stippling was seen in one patient. Fourteen patients had low hemoglobin with a median value of 9.7 g/dL. Mean serum blood lead level was 87.1 µg/dL. None of them required anti-chelating agent. Lead toxicity owing to herbal medicine is not uncommon cause of unexplained abdominal pain. Most of these patients do not require a chelating agent for treatment. There is a need to bring these herbal medicines under strict regulations for displaying its constituents and their concentrations.