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.

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.

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.

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.

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.

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.

Efficacy and expenses of succimer vs. d-penicillamine plus garlic in the treatment of lead poisoning: a retrospective cross-sectional study.

PURPOSE: Lead Poisoning is a major health problem in Iran. We aimed to compare efficacy of a standard regimen (Succimer) with that of a low-priced combination of D-penicillamine and Garlic in outpatients with lead poisoning. METHODS: In this retrospective cross-sectional study, year-long clinical files of outpatients with lead poisoning in two referral toxicology clinics in Mashhad, Iran were reviewed. A total of 79 patients (all men), received either Succimer or a combination of D-penicillamen plus garlic (DPN + Gar), for 19 and 30 days, respectively. Clinical and laboratory data, including blood lead level (BLL), were analyzed and treatment expanses were compared between the two regimens. RESULTS: Of 79 male patients, 42 were treated by DPN + Gar and 37 received Succimer. Mean BLL of DPN + Gar group before treatment (965.73 ± 62.54 µg/L) was higher than that of the Succimer group (827.59 ± 24.41) (p < 0.001). After treatment, BLL in both groups significantly reduced to 365.52 ± 27.61 µg/L and 337.44 ± 26.34 µg/L, respectively (p < 0.001). The price of a 19-day treatment with Succimer was approximately 28.6 times higher than a one-month course of treatment with garlic plus DPN. None of the treatments caused serious side effects in the patients. CONCLUSION: Combination therapy with DPN + Gar is as effective as Succimer in Pb poisoning, while treatment with Succimer is significantly more expensive.

[Lead poisoning associated with an Indian-manufactured unauthorized dietary supplement].

We report the case of a patient with lead poisoning caused by a dietary supplement. A 40-year-old man was referred to us due to intermittent upper abdominal pain and normocytic anemia. His hemoglobin level was 9.3 g/dl, with basophilic stippling in 2.8% of red blood cells. Bone marrow aspirate smear showed ringed sideroblasts that represented 19% of the erythroblasts. The patient reported the use of an unauthorized, Indian-manufactured dietary supplement and was diagnosed with lead poisoning based on a significantly high blood lead level. The dietary supplement was discontinued, and he was successfully treated with lead chelation therapy, and his hemoglobin level normalized within 2 months.

Lead poisoning from Ayurvedic treatment: a further case.

PURPOSE: We report a case of a 30 years old Indian sailor with microcytic anemia (Hb 9.9), persistent abdominal pain, emesis, dark stool, hyperchromic urine, latent jaundice and asthenia. Lead intoxication was confirmed (blood lead value of 102 µg/dL). The patient assumed Ayurvedic medicines in the previous months. Ayurveda is an ancient form of Indian traditional popular medicine aiming to re-establish health and body function through herbal preparations, heavy metals are often added. Our purpose was to treat the patient and to establish the source of poisoning. METHODS: After testing blood and urine lead concentration of other 3 crew members and analyzing over than 150 products used on the ship professional exposure was excluded. We analyzed the two Ayurvedic drugs assumed by the patient with an Inductively Coupled Plasma Mass Spectrometry. The patient underwent three chelation cycles with Calcium Disodium Ethylenediaminetetraacetic acid (EDTA) while monitoring blood and urinary lead levels. RESULTS: The final blood lead level at discharge, after three chelation cycles, was 36.27 µg/dL. One of the two drugs contained extremely high concentrations of lead and mercury. The three different mixtures of this preparation showed lead concentrations of 12,638.54 mg/kg (Sample 2A), 23,043.02 mg/kg (Sample 2B), 21,352.97 mg/kg (Sample 2C); these levels are much higher than the highest values reported in literature for the indian soil (32 mg/kg). CONCLUSIONS: This case and similar cases raise the safety alert on complementary and alternative medicines; Ayurvedic medicine users should be carefully informed about potential risks and signs of poisoning.

The impact of chicory (Cichoriumintybus L.) on hemodynamic functions and oxidative stress in cardiac toxicity induced by lead oxide nanoparticles in male rats.

BACKGROUND: A common environmental pollutant, lead can induce toxicity in several organ systems. A range of industrial and/or household materials and products contain lead, and food/liquid ingestion and inhalation are the mechanisms through which lead is introduced into the human body. OBJECTIVE: Since knowledge about the cardiac toxicity of acute lead nanoparticles is limited, this work sought to shed more light on the issue by investigating the therapeutic effects of chicory extract based on rat models to elevate cardiac functions and oxidative stress. METHODS: Four research groups were used, each consisting of ten albino rats of male sex and adult age. The groups were: control group, chicory group, lead oxide nanoparticle group, and lead oxide nanoparticle + chicory group. RESULTS: Compared to the control and chicory groups, the lead oxide nanoparticle group displayed a notable increase in heart functions and oxidative stress markers as well as alterations in cardiac histological structure. On the other hand, cardiac function modifications were counteracted through four-week administration of lead oxide nanoparticles alongside chicory. CONCLUSION: Heart damage caused by lead oxide nanoparticles may be attenuated by chicory through scavenging of free radicals.

Acute lead poisoning: a diagnostic challenge in the emergency department.

Acute abdominal pain is a common presentation to the emergency department (ED). Ruling out life-threatening causes and giving pain relief are the most important tasks in ED. We describe a 32-year-old man who presented to ED with abdominal pain and vomiting which was unrelieved by usual doses of analgesic. Extensive investigations revealed no significant abnormalities. On further probing, he admitted taking traditional medications for infertility. The toxicological panel revealed a high blood lead level, leading to a diagnosis of acute lead toxicity. Chelation therapy with D-penicillamine was initiated and the patient's abdominal pain resolved within 4 days.

The synergistic hepatoprotective potential of Beta vulgaris juice and 2,3- dimercaptosuccinic acid in lead-intoxicated rats via improving the hepatic oxidative and inflammatory stress.

BACKGROUND: Lead (Pb) is observed in all areas of the environment, mainly derived from human operations such as mining, processing, and burning fossil fuels. Pb toxicity is one of the most prevalent causes of human hepatotoxicity. The available chelator drugs used now have many adverse effects and therefore the world is looking for natural and secure alternatives. METHODS: Here, we evaluated the hepatoprotective role of the oral administration (1 g/kg b.w.) of the lyophilized Beta vulgaris juice (BVJ) against Pb-induced rat hepatotoxicity. We also examined the possible synergistic hepatoprotective impact of the combination between BVJ and 2,3- dimercaptosuccinic acid (DMSA, the currently approved drug for Pb-toxicity). The evaluation depends on the ability of BVJ, DMSA, or their combination (BVJ-DMSA) to reduce serum and hepatic Pb level and to avoid oxidative stress and inflammation caused by Pb. The level of lipid peroxidation, reduced glutathione (GSH), total antioxidant capacity, and the activity of the antioxidant enzymes were quantified. In addition, the level of interleukin (IL)-6, nitric oxide (NO), DNA fragmentation, and liver histology were studied. RESULTS: The results showed that BVJ contained considerable amounts of betalains, vitamin C, and various types of phenolic compounds. Therefore, BVJ displayed a significant (p < 0.05) preventive influence on the elevation of Pb levels in blood and liver as well as the hepatic DNA fragmentation. In addition, it significantly (p < 0.05) improved most of the studied antioxidant and inflammatory markers in the Pb-intoxicated rats. However, the combined extract (BVJ-DMSA) revealed synergistic (combination index < 1) activities in most of the tested parameters. The histopathological results verified the biochemical findings of this research. CONCLUSION: BVJ has a potent efficiency in the protection from Pb-induced hepatotoxicity through the reduction of its accumulation in blood and liver and the prevention of the oxidative stress and inflammation induced by Pb. Additionally, the treatment of hepatotoxicity with BVJ and DMSA in combination showed a synergistic effect and reduced the adverse effects induced by DMSA. Thus, BVJ can be a promising hepatoprotective extract against lead toxicity and its combination with DMSA potentiates this effect.

Harnessing Peptides against lead pollution and poisoning: Achievements and prospects.

Among the broad applicability of peptides in numerous aspects of life and technologies, their interactions with lead (Pb), one of the most harmful substances to the environment and health, are constantly explored. So far, peptides were developed for environmental remediation of Pb-contaminations by various strategies such as hydrogelation and surface display. They were also designed for Pb detection and sensing by electrochemical and fluorescent methods and for modeling natural proteins that involve in mechanisms by which Pb is toxic. This review aims at summarizing selected examples of these applications, manifesting the enormous potential of peptides in the combat against Pb pollution. Nevertheless, the absence of new medicinal treatments against Pb poisoning that are based on peptides is noticeable. An overview of previous achievements utilizing Pb-peptide interactions towards various goals is presented and can be therefore leveraged to construct a useful toolbox for the design of smart peptides as next-generation therapeutics against Pb.

Changes in inflammatory cytokines, antioxidants and liver stiffness after chelation therapy in individuals with chronic lead poisoning.

BACKGROUND: Chronic exposure to lead causes lead to accumulate mainly in the liver. In vivo studies have shown that lead toxicity is related to alterations in the inflammatory response. We aimed to evaluate the association between lead poisoning and liver fibrosis as well as the change in the degree of liver fibrosis, levels of inflammatory mediators and glutathione (GSH) after chelation therapy. METHODS: Workers from a battery factory who were exposed to lead for > 12 months and had a blood lead level (BLL) > 70 µg/dL were enrolled (n = 86) in the study. Participants underwent chelation therapy with intravenous CaNa2EDTA for 2 days followed by treatment with oral D-penicillamine for 90 days. The primary outcome was the change in the degree of liver fibrosis, which was presented as liver stiffness (LS) measured by FibroScan®. Secondary outcomes were the changes in the levels of serum GSH and inflammatory mediators such as tumor necrosis factor-alpha (TNF-α), interleukin-1ß (IL-1ß), and interleukin-6 (IL-6) after chelation therapy. RESULTS: Among the 86 participants, there was a positive correlation between the duration of lead exposure and LS (r = 0.249, p = 0.021). To avoid the confounding effect of obesity-related steatosis, only 70 individuals who had controlled attenuation parameters < 296 dB/m, BMI < 25 kg/m2 and normal waist circumference were included in the interventional analysis. After chelation, the mean LS significantly decreased from 5.4 ± 0.9 to 4.8 ± 1.4 kPa (p = 0.001). Similarly, all of the inflammatory cytokines studied significantly decreased after chelation (p < 0.001); TNF-α decreased from 371.6 ± 211.3 to 215.8 ± 142.7; the levels of IL-1ß decreased from 29.8 ± 1.7 to 25.9 ± 4.3; and the levels of IL-6 decreased from 46.8 ± 10.2 to 35.0 ± 11.9. On the other hand, the mean GSH level increased significantly from 3.3 ± 3.3 to 13.1 ± 3.7 (p < 0.001) after chelation therapy. CONCLUSION: The duration of lead exposure was significantly correlated with the degree of liver fibrosis. Chelation treatment was associated with increased levels of GSH and decreased levels of proinflammatory cytokines and could potentially reduce the degree of LS. TRIAL REGISTRATION: This study was retrospectively registered and approved by the Thai Clinical Trial Registry (TCTR) on 2019-11-07. The TCTR identification number is TCTR20191108001 .