Lead Acetate Exposure Research Articles

Dose dependency of subchronic lead acetate exposure on biophysical characteristics of rats’ right atrium and ventricle

Dose dependency of subchronic lead acetate exposure on biophysical characteristics of rats’ right atrium and ventricle

Evaluation of Gender-Specific Variation in Lead-induced Nephrotoxicity in Wistar Rats

The kidney is sensitive to heavy metals because of its intensive metabolic activity and multiple functions namely those of excretion and pollutants concentration. The study aimed to evaluate the gender-specific variation in lead-induced nephrotoxicity in Wistar rats. 10 male and 10 female Wistar rats (180-220g) were each divided into 2 groups (n=5 each): Control (M), Lead alone (M), Control (F), Lead alone (F). Male and female rats of the experimental groups were administered a daily dose of 100 mg/kg/bw of lead acetate dispersed in distilled water for 21 days. All rats were anesthetized and sacrificed 24 hours after the last administration. Blood samples were collected via cardiac puncture for biochemical analysis, kidney tissues were harvested, homogenized, and analyzed for antioxidant enzymes (superoxide dismutase, catalase, glutathione peroxidase) and lipid peroxidation (measured by malondialdehyde levels). Results indicated a significantly (p<0.01) lower weight gain in the lead-only female (F) group compared to the lead-only male (M) group. Lead acetate exposure caused oxidative damage, evidenced by significantly reduced antioxidant enzyme levels and increased lipid peroxidation in both male and female groups, with the effects being more pronounced in females (p<0.05). Serum creatinine and Urea levels in the lead alone (M) and lead alone (F) group were increased when compared to their respective control groups (p<0.05) however serum creatinine was significantly (p<0.001) higher in lead alone (F) than lead alone (M). The electrolyte function increased significantly in this study (p<0.05) when compared with their control groups. Sodium ion in lead alone (F) increased significantly (p<0.01) when compared to lead alone (M). The study concludes that lead exposure induced nephrotoxicity in both male and female rats, but more significantly pronounced in females than the males. This increased severity may have been mediated by the higher lead-induced oxidative stress observed in the female rats compared to males.

Enzymological Effects of Lead Acetate Exposure in Various Organs of Oreochromis mossambicus (Peters 1852)

The various enzymological effects of heavy metal Lead acetate (Pb(C2H3O2)2) exposed to fingerlings of Oreochromis mossambicus was analyzed in this study. The 30 days old fingerlings of O. mossambicus were exposed to sub lethal dose 3.80ppm of 96 hrs. LC50 of Pb(C2H3O2)2 for 21 and 28 days, various organs (liver, gill, kidney and muscle tissue) were removed from control and treated fishes and were used for various enzymological effect: Succinate dehydrogenase (SDH), Lactate dehydrogenase (LDH), Aspartate aminotransferase (AST), Alanine aminotransferase (ALT), Acid phosphatase (ACP) and Alkaline phosphatase ALP). The observed data were subjected into various statistical analysis by using IBM-SPSS version 26. Among the two different exposure periods 21 and 28 days which compared with control fingerlings organs, the various enzymological effects were drastically suffered (Treated fish enzymological levels were inversely proportionate towards the control groups of fish species) by 28 days of exposure periods. Pb(C2H3O2)2 exposed to fingerlings which tested on various organs at 28 days interval periods for assessing of SDH, LDH, AST, ALT, ACP and ALP of various organs of treated fish: Liver: 12.02, 55.75, 58.24, 125.27,12.26, 11.82 µ moles of phenol liberated/ mg of protein; Gill: 10.80, 33.75, 28.73, 28.11, 7.80, 8.63 µ moles of phenol liberated/ mg of protein; Kidney: 12.18, 46.33, 44.78, 75.40, 6.27, 10.38 µ moles of phenol liberated/ mg of protein and Muscle: 11.72, 32.44, 32.76, 44.20, 3.72, 7.20 µ moles of phenol liberated/ mg of protein were recorded on tissue of treated fish. The enzymological effect of Pb(C2H3O2)2 exposed towards O. mossambicus which observed various health defects on organism exposed to a particular toxicant. It may give sufficient information about heavy metal contamination on aquatic organism and would help us to propose policies to protect the ecosystem.

Lead Acetate Exposure and Cerebral Amyloid Accumulation: Mechanistic Evaluations in APP/PS1 Mice.

The role of environmental factors in Alzheimer's disease (AD) pathogenesis remains elusive. Mounting evidence suggests that acute and past exposure to the environmental toxicant lead (Pb) is associated with longitudinal decline in cognitive function, brain atrophy, and greater brain -amyloid () deposition. However, the nature of Pb-induced amyloid deposition and how it contributes to AD development remain unclear. This study investigates the role of Pb in the pathogenesis of cerebral amyloid angiopathy (CAA) and whether plasminogen activator inhibitor-1 (PAI-1) contributes to this process in the APP/PS1 mouse model. Female APP/PS1 mice at 8 wk of age were administered either Pb-acetate (PbAc) (i.e., ) or an equivalent molar concentration of sodium acetate (NaAc) via oral gavage once daily for 8 wk. Amyloid deposition and vascular amyloid were determined by immunostaining. In addition, perivascular drainage, vascular binding assay, and microglial endocytosis were examined to determine underlying mechanisms. Furthermore, magnetic resonance imaging demyelination imaging was performed invivo measure the level of demyelination. Finally, Y-maze and Morris water maze tests were assessed to evaluate the cognitive function of mice. APP/PS1 mice (an AD mice model) exposed to PbAc demonstrated more vascular amyloid deposition less neocortical myelination, and lower cognitive function, as well as greater vascular binding to , higher ratios, strikingly lower levels in the perivascular drainage, and microglial endocytosis. Importantly, exposure to a specific PAI-1 inhibitor, tiplaxtinin, which previously was reported to lower CAA pathology in mice, resulted in less CAA-related outcomes following PbAc exposure. Our findings suggest that PbAc induced CAA/AD pathogenesis via the PAI-1 signaling in the APP/PS1 mouse model, and the inhibition of PAI-1 could be a potential therapeutic target for PbAc-mediated CAA/AD disorders. https://doi.org/10.1289/EHP14384.

Evaluation of the protective activity of aqueous leaf extract of <i>Cissus populnea</i> against lead-induced testicular toxicity in Wistar rats.

Cissus populnea, a plant native to West Tropical Africa, has garnered attention, particularly for its use in traditional medicine to improve genital erection in males. Accordingly, this study investigated the possible protective effects of aqueous leaf extract of Cissus populnea (ACPE) against lead acetate-induced testicular toxicity in Wistar rats. Twenty adult Wistar rats were divided into four groups and administered various treatments, including 50mg/kg body weight (BW) of lead acetate, 1000 mg/kg BW of ACPE, or a combination of both, for 28 days via an orogastric tube. Thereafter, animals were sacrificed and various parameters, including body weight changes, sperm quality, and histology of testes were evaluated. Lead acetate exposure led to significant (P<0.05) weight loss, reduction in sperm count and motility as well as histological alterations of the testes. However, ACPE treatment significantly (P<0.05) mitigated the adverse effects induced by lead in the testes of exposed rats. Taken together, these findings underscore the potential of Cissus populnea as a possible protective agent against lead-induced testicular toxicity, thus offering important insights for future treatment options derived from natural sources.

The potential modulatory impact of garlic-selenium nanoparticles coated with synthetic tocopherol polyethylene glycol-succinate against lead acetate toxicity in male rabbits

Toxic heavy metal lead enters in the environment due to industrial and anthropogenic activity threatens ecosystems and public health. Natural garlic extract (GE) exhibits antioxidant properties and various applications against several ailments. Therefore, this study scrutinized the protective effects of tocopherol polyethylene glycol succinate-coated garlic selenium (TPGS-GSNP) against lead acetate (LA) toxicity in rabbits. Sixty-four mature male rabbits were involved and divided into 8 equal groups. They received distilled water (negative control; T1), 30 mg/kg bw of LA (positive control; T2), 800 mg/kg bw of GE (T3), GE + LA (T4), 1 mg/kg bw of TPGS-Selenium (T5), TPGS-S + LA (T6), 1 mg/kg bw of TPGS-GSNP (T7), and TPGS-GSNP + LA (T8). Consequently, treatments were administered three times a week for 12 weeks. Following the treatment period, serum oxidant-antioxidant, protein, and lipid profiles, liver and kidney function, histopathological findings of the adrenal, liver, and kidneys, femur bone marrow chromosomal aberrations, and mitotic activity were collected and analysed. LA exposure showed significant reductions in antioxidant levels, organ weights, and mitotic activity while increasing oxidative stress, corticosteroid levels, and chromosomal aberrations. Importantly, TPGS-GSNP administration significantly improved these markers compared to the LA group. In addition, histological analysis revealed structural improvements of the studied organs in the TPGS-GSNP group compared to the LA group, which displayed high cellular necrotic and degenerative changes. In conclusion, synthetic TPGS-GSNP demonstrated higher protective efficacy against LA-induced toxicity compared to natural GE or selenium alone. However, more future studies could be conducted to explore the potential of TPGS-GSNP as an anticancer or immunomodulatory agent.

To explore the protective effect of gastrodin on PC12 cells against oxidative stress induced by lead acetate based on network pharmacology.

Screening and predicting potential targets for gastrodin antioxidant stress based on network pharmacology methods, and exploring the effect of gastrodin on lead acetate induced oxidative stress in PC12 cells through cell experiments. Through the Pharmaper database Predict the target of action of gastrodin. Through OMIM and GeneCards to collect oxidative stress targets from database, and intersect with drug targets to obtain drug disease intersection targets; Construct a PPI network diagram using the STRING database. Perform GO enrichment analysis and KEGG pathway enrichment analysis on intersection targets through the DAVID platform. Lead acetate (PbAc) exposure was used to establish a lead poisoning cell model, and intracellular ROS levels, ALB, AKT1, and Caspase-3 levels were measured. A total of 288 targets of gastrodin action, 638 targets related to oxidative stress, and 62 drug disease intersection targets were obtained, among which core targets such as ALB, AKT1, CASP3 may be closely related to oxidative stress. KEGG pathway analysis showed that gastrodin antioxidant stress mainly involved in lipid, cancer pathway and other signaling pathways. The results of the cell experiment showed that 50 μM is the optimal effective concentration for PbAc induced ROS production in PC12 cells. Gastrodin significantly increased the ROS content of PC12 cells treated with PbAc, Upregulation of ALB expression and downregulation of AKT1 and CASP3 expression. Gastrodin may alleviate PbAc-induced ROS in PC12 cells, indicating potential protective effects against oxidative stress. Further studies are needed to confirm these findings and explore the underlying mechanisms.

Administration of ethanol extract of galangal (Alpinia Galanga) on histopathology of male mouse (Mus musculus) lungs exposed to lead acetate

Objective: This research aims to assess the preventive effect of ethanol extract of red galangal (Alpinia Galanga) on type I pneumocyte cell necrosis and proliferation of type II pulmonary pneumocytes in male mice (Mus musculus) exposed to lead acetate-induced damage. Method: A total of 25 male mice aged 2.5-3 months and weighing 25-30 g were divided into five groups. The negative control group (K-) received oral water without lead acetate exposure, while the positive control group (K+) received 20 mg/kg BW of lead acetate. The treatment groups P1, P2, and P3 were exposed to lead acetate at a dose of 20 mg/kg BW/day and received red galangal extract at doses of 200 mg/kg BW, 400 mg/kg BW, and 800 mg/kg BW, respectively. All treatment groups were administered lead and ethanol extract of galangal orally from days 4 to 24 at a rate of 0.2 ml/head. Results: The Mann-Whitney U statistical test revealed a significant increase in type I pneumocyte cell necrosis and type II pneumocyte cell proliferation in the lungs of male mice (Mus musculus) exposed to lead acetate (p<0.05). Administration of ethanol extract of galangal after exposure to lead acetate significantly reduced type I pneumocyte cell necrosis and type II pneumocyte cell proliferation (p<0.05). The highest dose of galangal ethanol extract, 800 mg/kg BW, showed a significant decrease in type II pneumocyte cell proliferation (p<0.05). Conclusion: This study concludes that red galangal extract has a preventive effect in reducing the damage to type I and type II pneumocytes in the lungs of male mice (Mus musculus) exposed to lead acetate.

Exploring the Hepato-Renal Impact of Lead Acetate and in Combination with Defatted Moringa oleifera Seed Meal in Wistar Rats

Lead acetate is recognized for its hepatorenal toxicity, causing harm to the liver and kidneys upon exposure through air, water, or food, thus, leading to severe health issues. Defatted Moringa oleifera seed meal (DMOSM) is valued for its health benefits by offering a protein-rich supplement with antioxidant properties, and serving as a sustainable source of plant-based protein. In this study, the impact of lead acetate exposure and the potential protective effects conferred by DMOSM in male Wistar rats were assessed. The rats were divided into five groups: negative control (Group I), lead acetate exposure (Group II), lead acetate with DMOSM (Group III), sequential lead acetate and DMOSM treatment (Group IV), and DMOSM only (Group V). Serum biochemical parameters were evaluated at 7, 14, 21, and 28 days. Results revealed that, at 7 days, lead exposure and DMOSM led to slightly lower total protein. Group II exhibited significantly lower albumin levels, suggesting early liver dysfunction, while urea and creatinine variations indicated a potential renal stress. By 14 days, there was elevated total protein in the leadexposed groups, while DMOSM showed potential hepatoprotective effects, evidenced by significantly lower ALT activity in Group III. At 21 and 28 days, persistent or worsening liver dysfunction was observed in lead-exposed groups, while DMOSM demonstrated protective effects, especially in liver enzymes and renal markers. These findings highlight the complex interplay between lead toxicity and DMOSM-mediated protection. Thus, there is need for further investigation into the underlying mechanisms and therapeutic potential of DMOSM.

Antagonistic effectiveness of Anacardium occidentale leaf extract on lead-acetate exposure-induced hepatorenal toxicity in rats.

Lead (Pb) poisoning is an environmental substance that accumulates in the hepato-renal tissue, which is hazardous to health, while Anacardium occidentale L. is a tropical herb used to treat oxidative stress and inflammatory diseases. The aim of this study was to investigate the antagonistic effect of Anacardium occidentale leaf extract on lead acetate exposure-induced hepatorenal toxicity in rats. Thirty-six adult Wistar rats were split into six equal groups (n = 6). Group I served as a control, and groups II and III were administered lead acetate (50 mg/kg) and Anacardium occidentale leaf extract (400 mg/kg), respectively, while rats in groups IV-VI were administered Anacardium occidentale (L) extract (200 mg/kg and 400 mg/kg) and 10 mg/kg of Succimer, respectively, and were then administered lead acetate (50 mg/kg). When compared to the group I, rats administered lead acetate showed an increase in hepatic enzymes, urea, creatinine, MDA, TNF-α, and IL-1β (p < 0.001) levels and decreased levels of SOD, CAT, and GSH, whereas Anacardium occidentale prevented the increase in hepatorenal function parameters, oxidative stress, and inflammatory markers (TNF-α and IL-1β) induced by lead acetate. Rats administered only lead acetate had a marked increase in hepatic Pb concentration, severe hepatic steatosis, and renal glomerulus degeneration. However, treatment with Anacardium occidentale extract and succimer decreases the Pb concentration, oxidative stress, and inflammation, and also reduces histological liver steatosis and glomerular cytoarchitecture deterioration in the kidney. The results of this study revealed that Anacardium occidentale extract protects against lead acetate-induced liver and kidney toxicity by decreasing oxidative stress and inflammation.

Protective Role of Myricetin and Fisetin Against Nephrotoxicity Caused by Lead Acetate Exposure through Up-regulation of Nrf2/HO-1 Signalling Pathway.

The effect of various flavonoids against oxidative stress and inflammation caused by lead exposure has been investigated. However, the protective effects of myricetin (MYC) and fisetin (FST), which are known to have potent antioxidant properties, against nephrotoxicity caused by exposure to lead acetate (LA), the water-soluble form of lead, have not been investigated. Our study investigated the protective role of these flavonoids against LA intoxication-induced nephrotoxicity. In our study, 42 male rats were used. The rats were randomly selected and divided into 6 groups. These groups were: control, LA (100g/kg), LA + MYC (100mg/kg), LA + MYC (200mg/kg), LA + FST (100mg/kg) and LA + FST (200mg/kg). All chemicals were administered daily by gavage for 28 days. According to the experimental protocol, the animals were sacrificed and their kidney tissues were isolated. Serum biochemical parameters, histological examinations, levels of several trace elements, oxidative stress and inflammatory parameters at both biochemical and molecular levels in kidney tissues were examined. After LA administration, tissue lead levels increased and zinc levels decreased. This situation was reversed by MYC and FST treatment. Oxidative stress and inflammatory response were increased in the kidney tissue of LA-treated rats and renal function was impaired. It was observed that both doses of MYC and high dose of FST could prevent nephrotoxicity. Oral administration of both doses of MYC and high dose FST ameliorated the changes in biochemical, oxidative and inflammatory parameters. Restoration of normal renal tissue architecture was also demonstrated by histological studies. MYC and FST were found to have promising biological activity against LA-induced nephrotoxicity, acting by attenuating inflammation and oxidative stress and improving antioxidant status.

Unveiling the Mechanisms of Bone Marrow Toxicity Induced by Lead Acetate Exposure.

Lead (Pb), a widespread heavy metal, causes severe toxicity in human and animal organs (e.g., bone marrow), whereas the mechanisms of the bone marrow toxicity induced by Pb exposure are unclear. Hence, this study was designed to reveal the hub genes involved in Pb-induced bone marrow toxicity. GSE59894 dataset obtained from Gene Expression Omnibus (GEO) was composed of lead acetate (PbAc2)-treated and control bone marrow samples. Totally 120 and 85 differentially expressed genes (DEGs) were identified on the 1st day, while 153 and 157 DEGs on the 3rd day in the bone marrow treated with 200 and 600mg/kg of PbAc2, respectively. Notably, a total of 28 and 32 overlapping DEGs were identified in the bone marrow on the 1st and 3rd day treated with PbAc2, respectively. Biological process analysis suggested that the common DEGs were primarily participated in cell differentiation, the response to drug, xenobiotic stimulus, and organic cyclic compound. Pathway analysis demonstrated that the overlapping DEGs were primarily linked to PI3K-Akt, TGF-β, MAPK, and osteoclast differentiation signaling pathways. Moreover, the hub genes, including PLD2, DAPK1, ALB, TNF, FOS, CDKN1A, and TGFB3, might contribute to PbAc2-induced bone marrow toxicity. Overall, our study offers an important insight into the molecular mechanisms of Pb-induced bone marrow toxicity.

Hepatoprotective and Neuroprotective Effects of Naringenin against Lead-Induced Oxidative Stress, Inflammation, and Apoptosis in Rats.

Naringenin (NRG) is one of the most important naturally occurring flavonoids, predominantly found in some edible fruits, such as citrus species and tomatoes. It has several biological activities, such as antioxidant, antitumor, antiviral, antibacterial, anti-inflammatory, antiadipogenic, and cardioprotective effects. The heavy metal lead is toxic and triggers oxidative stress, which causes toxicity in many organs, including the liver and brain. This study explored the potential protective role of NRG in hepato- and neurotoxicity caused by lead acetate in rats. Four groups of ten male albino rats were included: group 1 was a control, group 2 was orally treated with lead acetate (LA) at a dose of 500 mg/kg BW, group 3 was treated with naringenin (NRG) at a dose of 50 mg/kg BW, and group 4 was treated with 500 mg/kg LA and 50 mg/kg NRG for 4 weeks. Then, blood was taken, the rats were euthanized, and liver and brain tissues were collected. The findings revealed that LA exposure induced hepatotoxicity with a significant increase in liver function markers (p < 0.05). In addition, albumin and total protein (TP) and the albumin/globulin ratio (A/G ratio) (p < 0.05) were markedly lowered, whereas the serum globulin level (p > 0.05) was unaltered. LA also induced oxidative damage, demonstrated by a significant increase in malonaldehyde (MDA) (p < 0.05), together with a pronounced antioxidant system reduction (SOD, CAT, and GSH) (p < 0.05) in both liver and brain tissues. Inflammation of the liver and brain caused by LA was indicated by increased levels of nuclear factor kappa beta (NF-κβ) and caspase-3, (p < 0.05), and the levels of B-cell lymphocyte-2 (BCL-2) and interleukin-10 (IL-10) (p < 0.05) were decreased. Brain tissue damage induced by LA toxicity was demonstrated by the downregulation of the neurotransmitters norepinephrine (NE), dopamine (DA), serotonin (5-HT), and creatine kinase (CK-BB) (p < 0.05). Additionally, the liver and brain of LA-treated rats displayed notable histopathological damage. In conclusion, NRG has potential hepato- and neuroprotective effects against lead acetate toxicity. However, additional research is needed in order to propose naringenin as a potential protective agent against renal and cardiac toxicity mediated by lead acetate.

Curcumin and cinnamon mitigates lead acetate-induced oxidative damage in the spleen of rats.

Lead toxicity is a common occupational and environmental health hazard that exerts many toxic effects on animals and humans, including immunotoxicity. Curcumin (CUR) and cinnamon (CIN) are common medicinal herbs with immunostimulatory and antioxidant properties. Therefore, this study investigated the protective effect of curcumin and cinnamon against lead acetate (LA)-induced splenotoxicity in rats via hemato-biochemical, immunological, oxidative stress marker, CYP-2E1 expression, histological, and immunohistological evaluations. Four groups of seven rats each were used: the control group received corn oil as a vehicle; the lead acetate group received (100mg/kg), the CUR + LA group received curcumin (400mg/kg) plus lead acetate, and the CIN + LA group received cinnamon (200mg/kg) plus lead acetate orally for 1 month. LA exposure induced macrocytic hypochromic anemia, leukocytosis, neutrophilia, monocytosis, and lymphopenia. Additionally, significant elevations in serum iron, ferritin levels, and transferrin saturation percentage with significant decline of total and unsaturated iron binding capacities (TIBC and UIBC), transferrin, and immunoglobulin G and M levels were recorded. In addition, lead acetate significantly upregulated splenic CYP-2E1 expression, that was evident by significant depletion of reduced glutathione (GSH) activity and elevation of malondihyde (MDA), nitric oxide (NO), and protein carbonyl (PC) concentrations in the spleen. Histologically, hyperplasia of lymphoid follicles, hemosiderin deposition, and disturbance of CD3 and CD68 immuno-expressions were evident in the spleen from the lead acetate group. However, curcumin and cinnamon administration restored the hemato-biochemical, immunological, and oxidative stress parameters as well as histological and immunohistological pictures toward normalcy. In conclusion, curcumin and cinnamon can partially ameliorate LA-induced oxidative damage in the spleen, possibly through their antioxidant, immunomodulatory, and gene-regulating activities.

The effect of ascorbic acid on histopathological, biochemical, pharmacological, and immunological toxicity of chronic lead acetate exposure on the spleen in a rat model

Objective To evaluate the effect of vitamin C on histopathological, biochemical, and immunotoxicity of chronic lead exposure in the spleen of a rat model.Methods The rats were divided into five groups of 10 rats each: group I received normal saline orally as a control group; groups II and III received lead acetate for 4 and 8 weeks, respectively; and groups IV and V received lead acetate and vitamin C for 4 and 8 weeks, respectively. The spleen was excised and processed for light, electron microscopic, histopathological, and biochemical analyses. Quantitative assessments of matrix metalloproteinase-2 (MMP-2), MMP-9, interleukin-2 (IL-2), IL-6, and tumor necrosis factor-alpha gene expressions were performed by real-time PCR.Results The examination of control and vitamin C with lead acetate supplemented groups revealed normal splenic architecture. In contrast, the spleen of lead-intoxicated groups exhibited degenerative changes in the spleen, with a significantly decreased expression of IL-2, glutathione peroxidase, superoxide dismutase, and hemoglobin (P<0.05), with significantly increased proinflammatory cytokine (IL-6 and tumor necrosis factor-alpha) expressions, concomitantly with increased oxidative products (malondialdehyde) and protease enzymes (MMP-2 and MMP-9) in the spleen tissues. The coadministration of vitamin C with lead for 4 weeks markedly resolved these changes.Conclusion This study may specify the efficiency of vitamin C in lead toxicity prevention in the spleen, represented by the reduced splenic harmful changes produced by lead administration.

Cymbopogon citratus protect against lead-induced suppression of haematological and tubuloglomerular functions as well as disruption of hepatocellular membranes in male Wistar rats

BackgroundLiver and kidney damage associated with lead acetate exposure has been reported to involve membrane disruption and renal tubuloglomerular dysfunctions which results in a sequalae of physiologic and pathologic responses. Whether Cymbopogon citratus, a widely used herb for a plethoria of disease treatment can attenuate the adverse effect of lead exposure remains poorly understood. Hence, this study investigated the effect of Cymbopogon citratus on lead acetate induced hepatorenal toxicity in male Wistar rat. MethodsFollowing 7 days acclimatisation, rats were exposed to 50 mg/kg of lead acetate orally for 14 days thereafter treated with 200 mg/kg and 400 mg/kg of Cymbopogon citratus aqueous leaf extract orally for 28 days. At the end of 42 days experimentation, animals were euthanized and blood was collected for haematological and serum biochemical analysis. ResultsThe results showed that Cymbopogon citratus treatment improves haematological (RBC, PCV, Hb, WBC, Lymphocytes and platelet) functions. Also, Cymbopogon citratus significantly attenuated lead-induced liver and kidney damage by lowering plasma concentrations of ALP, ALT, AST, creatinine, uric acid and urea. Blood proteins (albumin and bilirubins) were also upregulated in Cymbopogon citratus treatment. ConclusionIn conclusion, this study suggest that Cymbopogon citratus protect against Lead acetate-induced hepatorenal toxicity by enhancing haematological and tubuloglomerular functions as well as attenuation of hepatocellular membrane disruption.

Study of lead-induced neurotoxicity in cholinergic cells differentiated from bone marrow-derived mesenchymal stem cells.

The developing brain is susceptible to the neurotoxic effects of lead. Exposure to lead has main effects on the cholinergic system and causes reduction of cholinergic neuron function during brain development. Disruption of the cholinergic system by chemicals, which play important roles during brain development, causes of neurodevelopmental toxicity. Differentiation of stem cells to neural cells is recently considered a promising tool for neurodevelopmental toxicity studies. This study evaluated the toxicity of lead acetate exposure during the differentiation of bone marrow-derived mesenchyme stem cells (bone marrow stem cells, BMSCs) to CCholinergic neurons. Following institutional animal care review board approval, BMSCs were obtained from adult rats. The differentiating protocol included two stages that were pre-induction with β-mercaptoethanol (BME) for 24h and differentiation to cholinergic neurons with nerve growth factor (NGF) over 5days. The cells were exposed to different lead acetate concentrations (0.1-100μm) during three stages, including undifferentiated, pre-induction, and neuronal differentiation stages; cell viability was measured by MTT assay. Lead exposure (0.01-100μg/ml) had no cytotoxic effect on BMSCs but could significantly reduce cell viability at 50 and 100μm concentrations during pre-induction and neuronal differentiation stages. MAP2 and choline acetyltransferase (ChAT) protein expression were investigated by immunocytochemistry. Although cells treated with 100μm lead concentration expressed MAP2 protein in the differentiation stages, they had no neuronal cell morphology. The ChAT expression was negative in cells treated with lead. The present study showed that differentiated neuronal BMSCs are sensitive to lead toxicity during differentiation, and it is suggested that these cells be used to study neurodevelopmental toxicity.

Protective Effect of Lemongrass Extract ( Cymbopogon nardus) on Spermatozoa Cells Induced by Lead Acetate

Introduction: Male infertility can be caused by many factors. One of which is environmental pollution such as lead acetate. Lead acetate exposure can increase Reactive Oxygen Species (ROS), affecting spermatozoa quality. Natural antioxidants and flavonoid on Lemongrass (C. nardus) have a great potential for protecting the male reproductive system. This study aimed to analyze the effect of giving various dosages of C. nardus extract on the sperm quality of mice. Methods: The Balb/C male mice were divided into five equal groups. The negative control group was injected with 0.01 ml Na-CMC 0.5% within 40 days, and the positive control group was injected with 0.01 ml lead acetate 7 mg/kg BW within 5 days, the treatment groups were injected by 0.01 ml lead acetate 7 mg/kg body weight within 5 days and continuously injected by 0.01 ml of C. nardus extract with various dosage 25 mg/kg BW, 50 mg/kg BW, and 100 mg/kg BW within 35 days. At the end of the experiment, mice were sacrificed, and sperm suspensions were collected from cauda epididymal to measure the morphology, concentration, and motility.Results: The results showed that giving C. nardus extract could repair morphology, concentration, and motility of spermatozoa with significantly different (p&lt;0.05). The 25 mg/kg BW dose has a good protective effect. Conclusion: The C. nardus extract can repair the decreasing sperm quality caused by lead acetate exposure.

Acute lead acetate induces neurotoxicity through decreased synaptic plasticity-related protein expression and disordered dendritic formation in nerve cells.

Lead (Pb) is a widespread environmental heavy metal that can damage the cerebral cortex and hippocampus, and reduce the learning and memory ability in humans and animals. In vivo and in vitro models of acute lead acetate exposure were established to further study the mechanism of neurons injury. In this study, 4-week-old female Kunming mice were randomly divided into four groups. Each group was treated with distilled water with different Pb concentrations (0, 2.4, 4.8 and 9.6mM). Mice were killed, and brain tissues were collected to detect the changes in synaptic plasticity-related protein expression. Furthermore, Neuro-2A cells were treated with 0, 5, 25 and 50μM lead acetate for 24h to observe the changes in cell morphology and function. In in vivo experiment, results showed that the expression levels of cytoskeleton-associated and neural function-related proteins decreased in a dose-dependent manner in the mouse brain tissue. In in vitro experiment, compared with the control group, Pb treatment groups were observed with smaller and round cells, decreased cell density and number of synapses. In the Pb exposure group, the survival rate of nerve cells decreased evidently, and the permeability of the cell membrane was increased. Western blot results showed that the expression of cytoskeleton-associated and function-related proteins decreased gradually with increased Pb exposure dose. Confocal laser scanning microscopy results revealed the morphological and volumetric changes in Neuro-2A cells, and a dose-dependent reduction in the number of axon and dendrites. These results suggested that abnormal neural structures and inhibiting expression of synaptic plasticity-related proteins might be the possible mechanisms of Pb-induced mental retardation in human and animals, thereby laying a foundation for the molecular mechanism of Pb neurotoxicity.

Targeting CC chemokine ligand (CCL) 20 by miR-143-5p alleviate lead poisoning-induced renal fibrosis by regulating interstitial fibroblasts excessive proliferation and dysfunction

ABSTRACT Environmental lead contamination can cause chronic renal disease with a common clinical manifestation of renal fibrosis and constitutes a major global public health threat. Aberrant proliferation and extracellular matrix (ECM) accumulation in renal interstitial fibroblasts are key pathological causes of renal fibrosis. However, the mechanism underlying lead-induced kidney fibrosis remains unclear. The present study analyzed gene expression prolifes in lead acetate-treated primary mice renal interstitial fibroblasts and confirmed the aberrant expression of CC chemokine ligand (CCL) 20, one of the most obvious up-regulated genes. Analogously, lead acetate exposure dose-dependently increased CCL20 transcription, protein expression and release. Knockdown of CCL20 suppressed lead acetate-induced fibroblast proliferation, hydroxyproline contents, transforming growth factor-beta production and ECM-related protein (Collagen I and fibronectin) expression. Bioinformatics analysis predicted five top miRNAs targeting CCL20. Among them, miR-143-5p expression was dose-dependently decreased in lead acetate-treated fibroblasts. Mechanistically, miR-143-5p directly targeted CCL20. Elevation of miR-143-5p antagonized lead acetate-induced fibroblast proliferation, hydroxyproline and ECM-related protein expression, which were reversed by CCL20 overexpression. Additionally, CCL20 knockdown suppressed lead acetate-mediated Smad2/3 and AKT pathway activation. Notably, miR-143-5p overexpression attenuated the activation of the Smad2/3 and AKT pathway in lead acetate-exposed fibroblasts, which was counteracted by CCL20 elevation. miR-143-5p injection ameliorated renal fibrosis progression in mice in vivo. Thus, targeting CCL20 by miR-143-5p could alleviate renal fibrosis progression by regulating fibroblast proliferation and ECM deposition via the Smad2/3 and AKT signaling, providing a potential therapeutic target for environmental lead contamination-evoked fibrotic kidney disease.