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.

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.

Evaluation of cytoprotective effects of compounds isolated from Copaifera langsdorffii Desf. against induced cytotoxicity by exposure to methylmercury and lead.

Copaifera langsdorffii L. is one of the most known medicinal species in Brazil. Its leaves are rich in phenolic compounds with potential biological activities as an antioxidant and chelating agent. This paper reports the isolation of four compounds from the hydroalcoholic extract of the leaves of C. langsdorffii and the investigation of their possible cytoprotective effects against heavy metal poisoning. Quercitrin (1), afzelin (2), 3,5-di-O-(3-O-methyl galloyl) quinic acid (3) and 4,5-di-O-(3-O-methyl galloyl) quinic acid (4), were associated with toxic doses of methylmercury and lead and evaluated by Alamar blue cell viability assays in HepG2 and PC12. The compounds displayed significant cytoprotective effect for the HepG2 cell line against both metals. Compounds 1-4 did not protect PC12 cells against methylmercury induced-cytotoxicity, but at lower concentrations, they protected against lead induced-cytotoxicity. The evaluated compounds showed a promising cytoprotection effect against exposure to heavy metals and should be further investigated as protective agents.

Lead Poisoning in Children.

Asymptomatic lead poisoning has become more common in children. Blood lead levels of less than 5 µg per dL are associated with impairments in neurocognitive and behavioral development that are irreversible. Risk factors for lead poisoning include age younger than five years, low socioeconomic status, living in housing built before 1978, and use of imported food, medicines, and pottery. The U.S. Preventive Services Task Force released a recommendation in 2019 citing insufficient evidence to assess the balance of benefits and harms of universal screening for elevated blood lead levels in asymptomatic children and pregnant women. Local risk factors can be substantial, and the Centers for Disease Control and Prevention (CDC) recommends that states and cities formulate their own targeted screening guidelines. In the absence of local guidance, the CDC recommends screening all Medicaid-eligible children at 12 months and again at 24 months, or at least once between 36 and 72 months if not previously screened. The CDC also recommends universal screening in areas where more than 27% of the housing was built before 1950, or where at least 12% of children 12 to 36 months of age have blood lead levels greater than 10 µg per dL. Life-threatening lead levels are treated with chelation therapy, and lower levels should prompt case management and environmental investigations to identify and remove the source of exposure. Primary prevention strategies are essential to eliminate the harmful effects of lead on child development.

Putative impacts of phytogenic additives to ameliorate lead toxicity in animal feed.

Lead (Pb) is a toxic heavy metal and an environmental pollutant, particularly because of its anthropogenic activity. The main impacts of Pb is recognized to cause injurious influences of various levels of the tropic chain, due to bio-accumulated lead causes many health issues such as intoxication of different body organs, such as kidneys and liver, and reproductive and nervous systems. Industrial lead toxicity has reduced as a result of the attempts to decrease the lead levels in the surrounding work environment. Conversably, health risks related with long-term environmental exposure to a low dose of Pb have been steadily demonstrated. Long-term exposure to lead toxicity caused inflammatory infiltration, degenerative changes in testicular tissues, reduction in spermatocytes, necrosis of hepatocytes, degeneration in renal tubules, and renal epithelium hypertrophy. Hence, we need an influential approach to vanquish lead toxicity. This consequence has emerged the necessity for potentially safe represent remedy, favorably keeping both enhancement and chelating of the antioxidant competences. Many antioxidants have been used for chelating heavy toxic pollutants such as lead and oxidative stress released in excess during lead exposure. Several studies have stated the noticeable gathering of herbal singly or in combination in modulating lead-induced disturbances, therefore proposing great promise in enhancing health status and welfare of man as well as animals. For this, in the current review, we tried to discuss the enormous harmful influences of lead toxicity on the animal model and the disturbing truth that this detrimental toxic substance can be found quite simply in the surroundings and amplitude.

Computational study of metal complexes formed with EDTA, melatonin, and its main metabolites: implications in lead intoxication and clues to a plausible alternative treatment.

Melatonin has been proposed as an alternative treatment to the usage of EDTA for lead intoxication. In this computational paper, since previous work has not systematically studied the complexes that may be formed in the existing and proposed treatments, we study 45 possible complexes that we suggest may be formed between Pb and some essential metals with melatonin, melatonin metabolites, and EDTA, analyzing the stability and viability of these through the Gibbs free energy of complexation (ΔΔG), molecular orbitals, and energy decomposition analysis at the DFT level of theory PBE/TZ2P. Our findings show that most complexes present exergonic energies of reaction, and thus spontaneous complex formation. In addition, we show that the AMK and 3OHM melatonin metabolites possess electronic and thermodynamic properties adequate to act as lead trapping molecules due to the lower Pauli repulsion energies involved in the complexes they form and their large negative values of ΔΔG. Therefore, it is shown that both melatonin and some of its metabolites may be employed in a viable treatment for lead intoxication through formation of stable Pb-complexes. Graphical abstract Metal complexes formed with EDTA, melatonin, and its main metabolites.

The role of the South African Medical Research Council in reducing lead exposure and preventing lead poisoning in South Africa.

Even at low levels in blood, lead has been associated with reduced IQ scores, behavioural problems, learning impediments, aggression and violent behaviour. Since the 1980s, the South African Medical Research Council (SAMRC) has been investigating the sources of exposure to lead in South Africa (SA), the groups at highest risk of lead poisoning and a selection of the myriad associated health and social consequences. SAMRC research evidence contributed to the phasng out of leaded petrol, restrictions on lead in paint and other interventions. Subsequently, childhood blood lead levels in SA declined significantly. More recent studies have revealed elevated risks of lead exposure in subsistence fishing and mining communities, users of arms and ammunition, those ingesting certain traditional medicines, and users of certain ceramicware and artisanal cooking pots. Lead-related cognitive damage costs the SA economy ~USD17.7 (ZAR261.3) billion annually, justifying further SAMRC investment in lead exposure research in the country.

Effect of Zingiber officinale on some biochemical parameters and cytogenic analysis in lead-induced toxicity in experimental rats.

Exposure to toxic elements is greatly unavoidable in our daily activities due to several routes of coming in contact with these elements. Thus lead (Pb), is one of the major causes of health hazard in human. In this study, evaluation of Zingiber officinale as mitigating measure against Pb induced biochemical and cytogenic toxicity in albino rats was investigated. Experimental rats were grouped into five with five animals per group, group I serves as control and groups 2-5 were induced intraperitoneal with lead acetate dissolved in distilled water at 3 mg/kg body weight whereas group 3-5 were orally administered with 200 mg/kg vitamin C, 200 mg/kg, and 100 mg/kg of Z. officinale, respectively for 7 d. The obtained results show that aspartate aminotransferase (AST), alkaline phosphatase (ALP), lipid peroxidation, urea, creatinine, bilirubin, and gamma-glutamyl transferase (GGT) were significantly increased (p < 0.05) and catalase (CAT) were reduced progressively in Pb alone induced rats. Hematological parameters showed a progressive reduction (p < 0.05) in lead acetate alone rats. There were significant changes in micronuclei (MN), chromosomal aberrations (CA) frequency, and oxidative damages in the bone marrow cells from lead acetate alone induced rats, although, mitotic index scores in these cells were reduced gradually (p < 0.05). The altered parameters were significantly reversed toward the levels observed in normal control rats administered with vitamin C and aqueous extract of Z. officinale. Hence, these results suggest that Z. officinale roots might contain therapeutic potential that can ameliorate the hazard effect of lead acetate poison.

ANALYSIS OF HISTORICAL MEDICAL RECORDS OF CALIFORNIA CONDORS ( GYMNOGYPS CALIFORNIANUS) ADMITTED FOR LEAD EXPOSURE TO THE LOS ANGELES ZOO AND BOTANICAL GARDENS BETWEEN 1997 AND 2012: A CASE SERIES STUDY.

Lead toxicosis remains the primary cause of death in wild populations of California condors ( Gymnogyps californianus). Many condors require medical intervention with lead chelation therapy, among other conservation measures, to survive in the wild. An analysis of historical medical records of California condors admitted for lead exposure to the Los Angeles Zoo and Botanical Gardens (LA Zoo) between 1997 and 2012 was performed to investigate clinical presentation, radiographic findings, and treatment along with the potential impact of these factors on recovery and successful release back into the wild. Of 100 individual condors presented to the LA Zoo for suspected lead toxicosis during this period, 84 condors had records for initial laboratory blood lead levels. For these 84 condors (40 [47.6%] females and 44 [52.4%] males), 277 initial laboratory blood lead levels in total were recorded because of repeated admissions. Thirty-two (38%) condors were admitted once to the zoo and 62% were admitted two or more times. Clinical signs were not observed in 87.5% of the condors admitted with median blood lead concentrations of 26 µg/dl. Of the radiographs taken on initial presentation, 65% did not show evidence of gastrointestinal metallic foreign bodies. Various treatments protocols with edetatum calcium disodium, dimercaptosuccinic acid, and lactated Ringer's solution were documented in the medical records. Of the 277 admissions, 154 admissions had a recorded outcome posttreatment of which 140 (91%) admissions were released back to the wild. This study contributes to a better understanding of how intervention and therapeutic approaches have been essential for the recovery, release, and sustainability of these birds as a wild population. Consistency in data collection of California condors admitted for diagnosis and treatment of lead toxicosis is needed to better assess the impacts of medical interventions.

Dietary grape seed procyanidin extract protects against lead-induced heart injury in rats involving endoplasmic reticulum stress inhibition and AKT activation.

To investigate the protective role of grape seed procyanidin extract (GSPE) against lead-induced heart injury and the possible molecular mechanism associated with this event, Wistar rats were orally given GSPE (200 mg/kg) daily with or without lead acetate (PbA) (0.5 g/L) in drinking water for 56 d. GSPE attenuated oxidative stress, heart dysfunction, and lead accumulation in lead-exposed rat hearts. Meanwhile, GSPE inhibited the protein kinase RNA-like endoplasmic reticulum (ER) kinase/eukaryotic initiation factor 2α signaling pathway, and promoted protein kinase B (AKT) and glycogen synthase kinase 3ß phosphorylation altered by lead, and regulated lead-activated apoptosis and its related signaling pathway. This study suggests that dietary GSPE ameliorates lead-induced heart injury associated with ER stress inhibition and AKT activation. Dietary GSPE may be a protector against lead-induced heart injury and a novel therapy for lead exposure.

Protective effect of garlic extract against maternal and foetal cerebellar damage induced by lead administration during pregnancy in rats.

BACKGROUND: In spite of its industrial usefulness and varied daily uses, lead (Pb) pollution is a widespread ecological problem that faces the humans in the 21th century. Pb was found to produces a wide range of toxic effects including neurotoxicity especially to the developing and young offspring. Recently, the utilisation of herbal plants has received a significant attention where there has been rising awareness in their therapeutic use; among these is the garlic. In light of the above, the current study is designed experimentally in female pregnant rats in order to investigate the beneficial role of garlic extract in the protection from the maternal and foetal cerebellar damage produced by administration of different doses of Pb during pregnancy. MATERIALS AND METHODS: Positively pregnant female rats were divided into five groups; one control group, two Pb-treated groups (exposed to 160 and 320 mg/kg b.w. of Pb, respectively) and two groups treated with both Pb and garlic (exposed to Pb as previous groups together with 250 mg/kg b.w./day of garlic extract). Treatments started from day 1 to day 20 of pregnancy, where the mother rats of different experimental groups were sacrificed to obtain the foetuses. Pb level in the maternal and foetal blood and cerebellum was estimated by spectrophotometry. Specimens of the cerebellum of different mother and foetal groups were processed to histological and immunohistochemical staining for microscopic examination. RESULTS: The results showed that administration of Pb to pregnant rats resulted in a dose-dependent toxicity for both mothers and foetuses in the form of decrease in maternal weight gain, placental and foetal weights, brain weight and diminished foetal growth parameters, which were prominent in rat's group treated with larger dose of Pb. In Pb-treated rats, Pb level in blood and cerebellum was high when compared with the control group. The histopathological examination of the cerebellum of treated dams and foetuses showed marked alterations mainly in the form of Purkinje cell degeneration and lack of development of foetal cerebellum. Co-treatment of garlic extract along with Pb resulted in a significant decrease in Pb levels as compared with those treated with Pb alone with improvement of the histopathological changes. CONCLUSIONS: This study was useful in evaluating the hazardous effects of uncontrolled use of Pb in general and in assessing the developmental and neurotoxicity of foetuses due to exposure during pregnancy in particular. Co-administration of garlic has beneficial effects in amelioration of Pb-induced neurotoxicity and reversing the histopathological changes of the cerebellum of mother rats and foetuses. (Folia Morphol 2018; 77, 1: 1-15).

Use of lead-glazed ceramic ware and lead-based folk remedies in a rural community of Baja California, Mexico.

BACKGROUND: Lead exposure from lead-glazed ceramics (LGCs) and traditional folk remedies have been identified as significant sources of elevated blood lead levels in Mexico and the United States. This study took place from 2005 to 2012 in a rural community in Baja California, Mexico. OBJECTIVES: 1) Investigate the knowledge, attitudes, and practices related to lead and lead exposures from LGCs and two lead-based folk remedies ( azarcon and greta); and 2) evaluate a pilot intervention to provide alternative lead-safe cookware. METHODS: A baseline household survey was conducted in 2005, followed by the pilot intervention in 2006, and follow-up surveys in 2007 and 2012. For the pilot intervention, families who reported using LGCs were given lead-safe alternative cookware to try and its acceptance was evaluated in the following year. RESULTS: The community was mostly of indigenous background from Oaxaca and a high proportion of households had young children. In 2006, all participants using traditional ceramic ware at the time ( n = 48) accepted lead-safe alternative cookware to try, and 97% reported that they were willing to exchange traditional ceramic ware for lead-safe alternatives. The use of ceramic cookware decreased from over 90% during respondents' childhood household use in Oaxaca to 47% in 2006 among households in Baja California, and further reduced to 16.8% in 2012. While empacho, a folk illness, was widely recognized as an intestinal disorder, there was almost universal unfamiliarity with the use and knowledge of azarcon and greta for its treatment. CONCLUSION: This pilot evaluation provides evidence 1) for an effective and innovative strategy to reduce lead exposure from LGCs and 2) of the feasibility of substituting lead-free alternative cookware for traditional ceramic ware in a rural indigenous community, when delivered in a culturally appropriate manner with health education. This strategy could complement other approaches to reduce exposure to lead from LGCs.

Role of geraniol against lead acetate-mediated hepatic damage and their interaction with liver carboxylesterase activity in rats.

In this study, the effect of geraniol (50 mg/kg for 30 d), a natural antioxidant and repellent/antifeedant monoterpene, in a rat model of lead acetate-induced (500 ppm for 30 d) liver damage was evaluated. Hepatic malondialdehyde increased in the lead acetate group. Reduced glutathione unchanged, but glutathione S-transferase, glutathione reductase, as well as carboxylesterase activities decreased in geraniol, lead acetate and geraniol + lead acetate groups. 8-OhDG immunoreactivity, mononuclear cell infiltrations and hepatic lead concentration were lower in the geraniol + lead acetate group than the lead acetate group. Serum aspartate aminotransferase and alanine aminotransferase activities increased in the Pb acetate group. In conclusion, lead acetate causes oxidative and toxic damage in the liver and this effect can reduce with geraniol treatment. However, we first observed that lead acetate, as well as geraniol, can affect liver carboxylesterase activity.

Childhood lead poisoning: an overview.

Childhood lead poisoning is a major public health concern in many countries. In 2015, the Hong Kong SAR Government and its citizens faced a major public health crisis due to the presence of lead in the drinking water of a number of public housing estates. Fortunately, no child was diagnosed with lead poisoning that required treatment with chelation. Lead is a ubiquitous, naturally occurring material that exists in air, dust, soil, and water. It is also widely present in industrial products including petrol, paints, ceramics, food cans, candies, cosmetics, traditional remedies, batteries, solder, stained glass, crystal vessels, ammunition, ceramic glazes, jewellry, and toys. It can also be found in human milk. There is no safe blood lead level and it may be impossible to completely eliminate lead from any city. Hence routine measurement of blood lead levels is not considered useful. Acute poisoning, especially with encephalopathy, deserves immediate medical treatment in hospital. Chelation therapy is recommended if blood lead level is 45 µg/dL or higher. For blood levels between 20 and 45 µg/dL, treatment is indicated if the child is symptomatic. For blood levels below 20 µg/dL in otherwise asymptomatic children, the principle of treatment is to provide long-term neurodevelopmental follow-up and counselling. In all cases, immediate removal of the source of lead exposure is vital. Even low levels of lead exposure can significantly impair learning, educational attainment, and neurodevelopment.

The effect of tannic acid on bone mechanical and geometric properties, bone density, and trabecular histomorphometry as well as the morphology of articular and growth cartilages in rats co-exposed to cadmium and lead is dose dependent.

Cadmium (Cd) and lead (Pb) are toxic elements that accumulate to the largest extent in bones. Rats were used to investigate whether tannic acid (TA; 0.5%, 1.0%, 1.5%. 2.0%, or 2.5%) would have a protective effect on the structure and properties of bones in the case of exposure to Cd and Pb (diet: 7 mg Cd/kg and 50 mg Pb/kg) for 6 weeks. The effects of administration of TA in Cd- and Pb-poisoned rats on bone characteristics and the morphology of articular and growth cartilages were determined. All the rats administered Cd and Pb had an enhanced Cd and Pb concentration in blood plasma and bone and reduced bone Ca content irrespective of the TA administration. Cd and Pb alone reduced the mechanical endurance and histomorphometric parameters of trabecular bone and the thickness of the growth plate and articular cartilage. Tannic acid improved cancellous bone parameters in the rat exposed to Cd and Pb. A diet rich in TA improved articular cartilage constituents in heavy metal-poisoned rats. These results suggest that alimentary TA supplementation can counteract in a dose-dependent manner some of the destructive changes evoked by Cd and Pb possibly by reducing the exposure.

The protective effects of zinc in lead-induced testicular and epididymal toxicity in Wistar rats.

The aim of this study was to investigate the beneficial effects of zinc (Zn) in preventing lead (Pb)-induced reproductive toxicity in Wistar rats. The rats were divided into four groups, namely, control group, Pb group, Zn group, and Pb + Zn group. Animals were exposed to Pb (819 mg of Pb/L) or Zn (71 mg of Zn/L) or both through drinking water for 65 days. Rats exposed to Pb showed decreased weights of testes and accessory sex organs. Significant decrease in the testicular daily sperm production, epididymal sperm count, motility, viability, and number of hypoosmotic tail coiled sperm was observed in Pb-exposed rats. Testicular 3ß- and 17ß-hydroxysteroid dehydrogenase activity levels and circulatory testosterone levels were also decreased significantly in Pb-exposed rats. A significant increase in the lipid peroxidation products with a significant decrease in the activities of catalase and superoxide dismutase were observed in the testes and epididymis of Pb-exposed rats. Moreover, the testicular architecture showed lumens devoid of sperm in Pb-exposed rats. Supplementation of Zn mitigated Pb-induced oxidative stress and restored the spermatogenesis and steroidogenesis in Pb-exposed rats. In conclusion, cotreatment of Zn is effective for recovering suppressed spermatogenesis, steroidogenesis, elevated oxidative status, and histological damage in the testis of rats treated with Pb.

Environmental Remediation to Address Childhood Lead Poisoning Epidemic due to Artisanal Gold Mining in Zamfara, Nigeria.

BACKGROUND: From 2010 through 2013, integrated health and environmental responses addressed an unprecedented epidemic lead poisoning in Zamfara State, northern Nigeria. Artisanal gold mining caused widespread contamination resulting in the deaths of > 400 children. Socioeconomic, logistic, and security challenges required remediation and medical protocols within the context of local resources, labor practices, and cultural traditions. OBJECTIVES: Our aim was to implement emergency environmental remediation to abate exposures to 17,000 lead poisoned villagers, to facilitate chelation treatment of children ≤ 5 years old, and to establish local technical capacity and lead health advocacy programs to prevent future disasters. METHODS: U.S. hazardous waste removal protocols were modified to accommodate local agricultural practices. Remediation was conducted over 4 years in three phases, progressing from an emergency response by international personnel to comprehensive cleanup funded and accomplished by the Nigerian government. RESULTS: More than 27,000 m3 of contaminated soils and mining waste were removed from 820 residences and ore processing areas in eight villages, largely by hand labor, and disposed in constructed landfills. Excavated areas were capped with clean soils (≤ 25 mg/kg lead), decreasing soil lead concentrations by 89%, and 2,349 children received chelation treatment. Pre-chelation geometric mean blood lead levels for children ≤ 5 years old decreased from 149 µg/dL to 15 µg/dL over the 4-year remedial program. CONCLUSIONS: The unprecedented outbreak and response demonstrate that, given sufficient political will and modest investment, the world's most challenging environmental health crises can be addressed by adapting proven response protocols to the capabilities of host countries. CITATION: Tirima S, Bartrem C, von Lindern I, von Braun M, Lind D, Anka SM, Abdullahi A. 2016. Environmental remediation to address childhood lead poisoning epidemic due to artisanal gold mining in Zamfara, Nigeria. Environ Health Perspect 124:1471-1478; http://dx.doi.org/10.1289/ehp.1510145.

Effect of N-acetylcysteine administration on homocysteine level, oxidative damage to proteins, and levels of iron (Fe) and Fe-related proteins in lead-exposed workers.

N-Acetylcysteine (NAC) could be included in protocols designed for the treatment of lead toxicity. Therefore, in this study, we decided to investigate the influence of NAC administration on homocysteine (Hcy) levels, oxidative damage to proteins, and the levels of iron (Fe), transferrin (TRF), and haptoglobin (HPG) in lead (Pb)-exposed workers. The examined population (n = 171) was composed of male employees who worked with Pb. They were randomized into four groups. Workers who were not administered any antioxidants, drugs, vitamins, or dietary supplements were classified as the reference group (n = 49). The remaining three groups consisted of workers who were treated orally with NAC at three different doses (1 × 200, 2 × 200, or 2 × 400 mg) for 12 weeks. After the treatment, blood Pb levels significantly decreased in the groups receiving NAC compared with the reference group. The protein concentration was not affected by NAC administration. In contrast, Hcy levels significantly decreased or showed a strong tendency toward lower values depending on the NAC dose. Levels of the protein carbonyl groups were significantly decreased in all of the groups receiving NAC. Conversely, glutamate dehydrogenase activity was significantly elevated in all of the groups receiving NAC, while the level of protein thiol groups was significantly elevated only in the group receiving 200 mg of NAC. Treatment with NAC did not significantly affect Fe and TRF levels, whereas HPG levels showed a tendency toward lower values. Treatment with NAC normalized the level of Hcy and decreased oxidative stress as measured by the protein carbonyl content; this effect occurred in a dose-dependent manner. Moreover, small doses of NAC elevated the levels of protein thiol groups. Therefore, NAC could be introduced as an alternative therapy for chronic Pb toxicity in humans.

Correction: Water Spinach, Ipomoea aquatica (Convolvulaceae), Ameliorates Lead Toxicity by Inhibiting Oxidative Stress and Apoptosis.

[This corrects the article DOI: 10.1371/journal.pone.0139831.].

Water Spinach, Ipomoea aquatic (Convolvulaceae), Ameliorates Lead Toxicity by Inhibiting Oxidative Stress and Apoptosis.

BACKGROUND: Ipomoea aquatica (Convolvulaceae), an aquatic edible plant, is traditionally used against heavy metal toxicity in India. The current study intended to explore the protective role of edible (aqueous) extract of I. aquatica (AEIA) against experimentally induced Pb-intoxication. METHODS: The cytoprotective role of AEIA was measured on mouse hepatocytes by cell viability assay followed by Hoechst staining and flow cytometric assay. The effect on ROS production, lipid peroxidation, protein carbonylation, intracellular redox status were measured after incubating the hepatocytes with Pb-acetate (6.8 µM) along with AEIA (400 µg/ml). The effects on the expressions of apoptotic signal proteins were estimated by western blotting. The protective role of AEIA was measured by in vivo assay in mice. Haematological, serum biochemical, tissue redox status, Pb bioaccumulation and histological parameters were evaluated to estimate the protective role of AEIA (100 mg/kg) against Pb-acetate (5 mg/kg) intoxication. RESULTS: Pb-acetate treated hepatocytes showed a gradual reduction of cell viability dose-dependently with an IC50 value of 6.8 µM. Pb-acetate treated hepatocytes exhibited significantly enhanced levels (p < 0.01) of ROS production, lipid peroxidation, protein carbonylation with concomitant depletion (p < 0.01) of antioxidant enzymes and GSH. However, AEIA treatment could significantly restore the aforementioned parameters in murine hepatocytes near to normalcy. Besides, AEIA significantly reversed (p < 0.05-0.01) the alterations of transcription levels of apoptotic proteins viz. Bcl 2, Bad, Cyt C, Apaf-1, cleaved caspases [caspase 3, caspase 8 and caspase 9], Fas and Bid. In in vivo bioassay, Pb-acetate treatment caused significantly high intracellular Pb burden and oxidative pressure in the kidney, liver, heart, brain and testes in mice. In addition, the haematological and serum biochemical factors were changed significantly in Pb-acetate-treated animals. AEIA treatment restored significantly the evaluated-parameters to the near-normal position. CONCLUSION: The extract may offer the protective effect via counteracting with Pb mediated oxidative stress and/or promoting the elimination of Pb by chelating. The presence of substantial quantities of flavonoids, phenolics and saponins would be responsible for the overall protective effect.