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.

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.

Succimer chelation does not produce lasting reductions of blood lead levels in a rodent model of retained lead fragments.

Retained lead fragments from nonfatal firearm injuries pose a risk of lead poisoning. While chelation is well-established as a lead poisoning treatment, it remains unclear whether chelation mobilizes lead from embedded lead fragments. Here, we tested whether 1) DMSA/succimer or CaNa2EDTA increases mobilization of lead from fragments in vitro, and 2) succimer is efficacious in chelating fragment lead in vivo, using stable lead isotope tracer methods in a rodent model of embedded fragments. DMSA was > 10-times more effective than CaNa2EDTA in mobilizing fragment lead in vitro. In the rodent model, succimer chelation on day 1 produced the greatest blood lead reductions, and fragment lead was not mobilized into blood. However, with continued chelation and over 3-weeks post-chelation, blood lead levels rebounded with mobilization of lead from the fragments. These findings suggest prolonged chelation will increase fragment lead mobilization post-chelation, supporting the need for long-term surveillance in patients with retained fragments.

Intoxicación por plomo de origen ocupacional en la rehabilitación de viviendas antiguas / Occupational lead poisoning in rehabilitation of old houses

Presentamos dos casos de intoxicación por plomo o saturnismo de origen ocupacional en trabajadores de la construcción, en los que la fuente de exposición probablemente fue la inhalación de polvo procedente de pintura tratada con plomo, durante la restauración de una vivienda antigua. Ambos presentaron cuadros clínicos similares con dolor abdominal; en uno de ellos se observaron además anemia normocítica e hipertensión. Ambos fueron tratados con EDTA cálcico disódico, con buena evolución clínica. Nuestros casos nos recuerdan que es preciso mantener un alto índice de sospecha para la intoxicación por plomo en el contexto clínico adecuado y subrayan la importancia de unas adecuadas medidas de prevención en entornos de trabajo potencialmente contaminados. (AU)

We present two cases of lead poisoning or saturnism in construction workers, which the source of exposure was probably the inhalation of dust coming from lead-treated paint during the refurbishing of an old house. Both patients had similar clinical symptoms such as abdominal pain; in one of them normocytic anaemia and hypertension were also observed. Both were treated with calcium disodium EDTA, with good clinical evolution. Our cases remark the importance of maintaining a high index of suspicion for lead poisoning in the appropriate clinical context and underline the importance of adequate preventive measures in potentially contaminated work environments. (AU)

Succimer Mitigates the Perioperative Risk for an Increase in Blood Lead Levels During Bulletectomy: A Case Report.

CASE: A 38-year-old man with a tibial plateau fracture required treatment for elevated blood lead level (BLL) from retained bullet fragments in the same knee from a gunshot wound 21 years earlier. Oral succimer presurgery and postsurgery decreased the BLL from 58 to 15 µg/dL. CONCLUSION: Parenteral chelation has been previously recommended to mitigate an increase in BLLs during surgical intervention to remove bullet fragments. Oral succimer was an effective and well-tolerated alternative to intravenous chelation. Further research is needed to determine the optimal route, timing, and duration of chelation in patients with elevated BLL in need of bulletectomy.

Induction of Labor at Term for Severe Antenatal Lead Poisoning.

INTRODUCTION: Antenatal lead exposure is associated with multiple adverse maternal and fetal consequences. Maternal blood lead concentrations as low as 10 µg/dL have been associated with gestational hypertension, spontaneous abortion, growth retardation, and impaired neurobehavioral development. Current treatment recommendations for pregnant women with a blood lead level (BLL) ≥ 45 µg/dL include chelation. We report a successful case of a mother with severe gestational lead poisoning treated with induction of labor in a term infant. CASE REPORT: A 22-year-old G2P1001 female, at 38 weeks and 5 days gestation, was referred to the emergency department for an outpatient venous BLL of 53 µg/dL. The decision was made to limit ongoing prenatal lead exposure by emergent induction as opposed to chelation. Maternal BLL just prior to induction increased to 70 µg/dL. A 3510 g infant was delivered with APGAR scores of 9 and 9 at 1 and 5 min. Cord BLL at delivery returned at 41 µg/dL. The mother was instructed to avoid breastfeeding until her BLLs decreased to below 40 µg/dL, consistent with federal and local guidelines. The neonate was empirically chelated with dimercaptosuccinic acid. On postpartum day 2, maternal BLL decreased to 36 µg/dL, and the neonatal BLL was found to be 33 µg/mL. Both the mother and neonate were discharged to an alternative lead-free household on postpartum day 4.

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.

Quercetin as a Dietary Supplementary Flavonoid Alleviates the Oxidative Stress Induced by Lead Toxicity in Male Wistar Rats.

Quercetin is a naturally existing plant pigment belonging to the flavonoid group; it is contained in a wide range of vegetables and fruits. The accumulated evidence points to the potential uses of quercetin in protection of some disease conditions. Lead is one of the highly toxicant heavy metals that are widely spread in the environment and implicated in a wide spectrum of industries. No previous study has been reported to evaluate the effect of quercetin on lead toxicity. Therefore, the present study was conducted to elucidate some aspects of quercetin bioactivities in regard to its ability to combat the oxidative stress induced by lead toxicity. For this purpose, a total of sixty male Wistar rats were randomly and equally divided into three groups of 20 animals each; untreated control animals (group 1), lead-exposed animals (group 2; exposed to lead daily by oral gavage at the dose of 80 mg/Kg b.w.), and group 3 of animals, which were exposed to lead and daily received quercetin (10 h gap time between lead exposure and the receiving of quercetin) by oral gavage at the dose of 350 mg/Kg b.w. The experiment period was 8 weeks. All the assayed hematological and biochemical parameters of animals exposed to lead were significantly altered compared with the untreated control levels. Animals exposed to lead (group 2) exhibited significant decrements of the erythrocytic and total leucocytic counts, hemoglobin concentration, packed cell volume percent, total proteins, albumin and globulin. These animals also disclosed significantly decreased levels of antioxidant markers including total thiols, catalase and glutathione. On the other hand, these animals demonstrated significant increments in the levels of bilirubin, urea, creatinine, BUN, serum enzymes, H2O2 and MDA. Animals exposed to lead and given quercetin (group 3) exhibited improvement of these parameters, which were brought back at varying degrees toward the untreated control levels. Basing on the improvements of the assayed hematological and biochemical parameters, it was concluded that quercetin as a dietary supplement can act efficiently as an antioxidant to counteract the oxidative stress induced by lead toxicity and to maintain the oxidant antioxidant balance.

Dimercaptosuccinic Acid: Summary of Evidence.

Dimercaptosuccinic acid, or succimer, is an oral, heavy-metal chelating agent used to treat lead and heavy-metal poisoning. Although the drug is mainly used for the treatment of lead intoxication, initial data has shown encouraging results for the treatment of mercury and arsenic poisoning as well. This article focuses on the use of dimercaptosuccinic acid as a chelating agent and provides some general information on dimercaptosuccinic acid.

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.

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.

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.

[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.

Adult Lead Poisoning Caused by Contaminated Opium: A Two-Year Longitudinal Follow-Up Study.

Background: A major episode of lead poisoning caused by lead-adulterated opium occurred in Iran in 2016. Patients were removed from exposure and treated with chelating agents. A subset of those patients was evaluated in this follow-up study to evaluate treatment efficacy in relation to patient outcome. Methods: Between March 2016 and December 2017, thirty-five male cases of lead poisoning due to ingestion of lead-adulterated opium were followed for two years. There are three patient groups: 1) those who abstained from opium use; 2) those who continued to use potentially contaminated opium; and 3) those who abstained from opium and were placed on maintenance therapy. Maintenance therapy included: methadone and opium tincture, offered by the Opioid Maintenance Therapy (OMT) clinics. Amongst the three patient groups Blood Lead Levels (BLL), complete blood count, and kidney and liver function tests were compared. Findings: The results of BLL, hemoglobin, hematocrit, and aspartate aminotransferase were significantly different between the admission time and follow-up. Of the three patient groups, no difference was detected in these measures. Conclusions: Treatment of lead poisoning combined with OMT proved an effective method to prevent recurrent lead poisoning.

Lead encephalopathy in an adult opioid abuser.

A 38-year-old man presented at the emergency department with abdominal pain, vomiting, generalised weakness and altered consciousness. He had been ingesting opioids for over 5 years and had several past hospital admissions for abdominal pain. His investigations showed deranged liver function tests, anaemia and basophilic stippling on the peripheral blood smear. Further investigations revealed a significant increase in the serum lead level. We started chelation with peroral penicillamine 250 mg every 6 hours for 2 days and switched to intramuscular dimercaprol 4 mg/kg every 12 hours and intravenous calcium ethylenediamine tetraacetic acid 50 mg/kg in two divided doses daily for the next 5 days. We then discharged him home; he had become clinically stable by that time. We repeated his lead level and followed him up in the clinic. In this report, we emphasise the consideration of lead toxicity in opioid abusers and bring to attention a rare way of lead chelation in resource-limited settings.

A systematic review of clinical and laboratory findings of lead poisoning: lessons from case reports.

Lead is one of the most toxic heavy metals in the environment. The present review aimed to highlight hazardous pollution sources, management, and review symptoms of lead poisonings in various parts of the world. The present study summarized the information available from case reports and case series studies from 2009 to March 2020 on the lead pollution sources and clinical symptoms. All are along with detoxification methods in infants, children, and adults. Our literature compilation includes results from 126 studies on lead poisoning. We found that traditional medication, occupational exposure, and substance abuse are as common as previously reported sources of lead exposure for children and adults. Ayurvedic medications and gunshot wounds have been identified as the most common source of exposure in the United States. However, opium and occupational exposure to the batteries were primarily seen in Iran and India. Furthermore, neurological, gastrointestinal, and hematological disorders were the most frequently occurring symptoms in lead-poisoned patients. As for therapeutic strategies, our findings confirm the safety and efficacy of chelating agents, even for infants. Our results suggest that treatment with chelating agents combined with the prevention of environmental exposure may be an excellent strategy to reduce the rate of lead poisoning. Besides, more clinical studies and long-term follow-ups are necessary to address all questions about lead poisoning management.