Protective Effects of Green Tea Supplementation against Lead-Induced Neurotoxicity in Mice.

The use of natural products as therapeutic agents is rapidly growing recently. In the current study, we investigated the protective effects of green tea supplementation on lead-induced toxicity in mice. Forty albino mice were divided into four groups as follows: A: control group; B: green tea receiving group; C: lead-intoxicated group; and D: lead-intoxicated group supplemented with green tea. At the end of the experiment, the animals were tested for neurobehavioral and biochemical alterations. Green tea was analyzed through Gas Chromatography-Mass Spectrometry (GC/MS) analysis. We found that supplementation with green tea ameliorated the lead-associated increase in body weight and blood glucose. Green tea supplementation also changed the blood picture that was affected due to lead toxicity and ameliorated lead-induced dyslipidemia. The group of mice that were supplemented with green tea has shown positive alterations in locomotory, anxiety, memory, and learning behaviors. The GC/MS analysis revealed many active ingredients among which the two most abundant were caffeine and 1,2-benzenedicarboxylic acid, mono(2-ethylhexyl) ester. We concluded that green tea supplementation has several positive effects on the lead-induced neurotoxicity in mice and that these effects may be attributed to its main two active ingredients.

Mitigation of lead neurotoxicity by the ethanolic extract of Laurus leaf in rats.

The present study was conducted in order to assess the chemical composition of Laurus, its antioxidant activities, and benefit from the Laurus extract effect on neurotoxicity caused by lead acetate (Pb). Chemical profile was assayed by using liquid chromatography coupled with high-resolution mass spectrometry (LC-HR-MS). In this study, 40 male rats were divided into four groups (10 rats per each group): (1) control group, (2) Laurus group: rats treated with 250 mg/kg b. wt. of Laurus leaves extract, (3) Pb group: rats treated with 100 mg/kg b. wt. of lead acetate, (4) Pb + Laurus group: rats treated with 250 mg/kg b. wt. of Laurus leaves extract in addition to lead acetate for 30 days. At the end of experiment, some estimates were calculated from blood samples, brain tissue, and histological examination. The results showed that the extract is highly affluent in total flavonoids, total phenolic, and also has antioxidant activity. The LC-MS appeared a wide range of compounds in the extract. The oxidative stress resulted from exposure to lead acetate has been reported to cause reduction in body and brain weights, levels of RBCs, acetylcholinesterase (AChE), GSH, SOD, and CAT in addition to increase in levels of WBCs and MAD. Moreover, Laurus leaves extract notably lessened the biochemical changes caused by lead acetate in the blood, homogenate, and brain tissue (P < 0.05). The current study indicates the antioxidant activity of Laurus leaves extract and assumes that it has a defensive role against the oxidative damage caused by lead in a rat's brain.

A protective role of autophagy in Pb-induced developmental neurotoxicity in zebrafish.

Lead (Pb) is one of the most toxic heavy metals and has aroused widespread concern as it can cause severe impairments in the developing nervous system. Autophagy has been proposed as an injury factor in Pb-induced neurotoxicity. In this study, we used zebrafish embryo as a model, measured the general toxic effects of Pb, and investigated the effect of Pb exposure on autophagy, and its role in Pb-induced developmental neurotoxicity. Zebrafish embryos were exposed to Pb at concentrations of 0, 0.1, 1 or 10 µM until 4 days post-fertilization. Our data showed that exposure to 10 µM Pb significantly reduced survival rates and impaired locomotor activity. Uptake of Pb was enhanced as the concentration and duration of exposure increased. Inhibition of lysosomal degradation with bafilomycin A1 treatment abolished the suppression of Lc3-II protein expression by Pb. Furthermore, autophagosome formation was inhibited by Pb in the brain. In addition, mRNA expression of beclin1, one of the critical genes in autophagy, were decreased in Pb exposure groups at 72 h post-fertilization. Whole-mount in situ hybridization assay showed that beclin1 gene expression in the brain was reduced by Pb. Rapamycin, an autophagy inducer, partly resolved developmental neurotoxicity induced by Pb exposure. Our results suggest that autophagy plays a protective role in the developmental neurotoxicity of Pb in zebrafish embryos and larvae.

Hemin provides protection against lead neurotoxicity through heme oxygenase 1/carbon monoxide activation.

The neurotoxicity of lead (Pb) is well established, and oxidative stress is strongly associated with Pb-induced neurotoxicity. Heme oxygenase 1 (HO-1) is an important antioxidative enzyme for protection against oxidative stress in many disease models. In this study, we applied hemin, the substrate and a well-known inducer of HO-1, to investigate the possible role of HO-1 in protecting against Pb neurotoxicity. Hemin can significantly attenuate Pb acetate-induced cell death and oxidative stress in the hippocampus and frontal cortex of developmental rats. Consistent with in vivo results, the protective effects of hemin were also observed in SH-SY5Y cells after inducing cell survival and maintaining redox balance. However, knocking down HO-1 could significantly abolish the cytoprotective action of hemin against Pb toxicity, confirming HO-1 contributed to the protection. Finally, the HO-1-derived production of carbon monoxide, but not of bilirubin or Fe2+ , mediated the protective effects of HO-1 activation induced by hemin treatment against Pb-induced cell death and oxidative stress in SHSY5Y cells. Overall, this study showed that hemin provided protection against Pb neurotoxicity by HO-1/carbon monoxide activation.

Neuroprotective effect of morin on lead acetate- induced apoptosis by preventing cytochrome c translocation via regulation of Bax/Bcl-2 ratio.

Lead (Pb) intoxication is a prevalent type of environmental toxicity as well as minimal amount of lead exposure is liable for neurobehavioral or perhaps intelligence defects. The present study was undertaken to investigate the beneficial effects of morin in protecting the lead acetate (PbAc)-induced oxidative stress in rat brain. PbAc intoxication resulted in motor deficit, memory impairment and oxidative stress Further, PbAc administration alters Bax/Bcl-2 expression thereby increases cytochrome c release from the mitochondria. Treatment with morin at a dose of 40 mg/kg b.wt. significantly restored back the abnormal changes that were noticed in PbAc intoxicated rats. Histopathological sections of cortex, cerebellum and hippocampus showed the extent of neuronal loss in PbAc induced rats and its restoration upon administration of morin. These outcomes imply that morin might be employed therapeutically to chelate toxic metals like Pb, thus possibly lowering PbAc-induced neurotoxicity and tissue damage.

Ascorbic Acid Ameliorates Gestational Lead Exposure-Induced Developmental Alteration in GAD67 and c-Kit Expression in the Rat Cerebellar Cortex.

In the present study, we investigated the effects of ascorbic acid on lead-exposed developing cerebellum. Female rats were divided into the following three groups: control (distilled water), lead (0.2% lead acetate), and lead plus ascorbic acid (100 mg/kg/day, 10% solution). To evaluate the effect of lead exposure and ascorbic acid treatment accurately on the cerebellar development for the gestational period, we halted further treatment with lead and ascorbic acid in the dams after delivery of the pups. Although the ascorbic acid slightly decreased the lead level in pups, lead level was still high in the group treated with lead plus ascorbic acid group compared with the control group. The blood lead levels indicated that the ascorbic acid could facilitate both the excretion and transfer of lead from a dam to its pups via milk. At postnatal day 21, lead exposure significantly reduced the number of Purkinje cells in the cerebellar cortex of pups. Additionally, lead treatment induced degenerative changes such as reduction of glutamic acid decarboxylase (GAD67) and c-kit expressions are observed in the developing cerebellar cortex. In the cerebellum of the pups from the lead plus ascorbic acid group, reduction of the number of Purkinje cells, GAD67 expression, and c-kit immunopositivity were remarkably restored compared with the lead group. Our present results suggested that ascorbic acid treatment to lead-exposed dam exerted protective effects on the developing cerebellum against lead-induced neurotoxicity.

Tanshinone IIA ameliorates lead (Pb)-induced cognitive deficits and oxidative stress in a rat pup model.

OBJECTIVE: Chronic lead (Pb) exposure affects the developing central nervous system, whereas Tanshinone IIA (TSA) improves cognitive deficits. METHODS: In this study, we investigated the effects of TSA against lead-induced neurotoxicity in a rat pup model. A total of thirty two healthy male Wistar rats were randomly divided into four groups: lead-treated group, lead plus TSA-treated 1 group, lead plus TSA-treated 2 group, and controls. After a 4-week lead exposure, memory function was determined using Morris water maze and the concentration of lead was measured in blood. Total superoxide dismutase (T-SOD), glutathione (GSH), malonaldehyde (MDA) and brain-derived neurotrophic factor (BDNF) activities were determined in hippocampus samples. RESULTS: Lead exposure causes decrease of body weight; increase of the blood lead concentration; decrease of antioxidant activities and BDNF content. However, co-administration of TSA with lead ameliorated the weight loss. Furthermore, TSA inhibited neurotoxicity as evidenced by decreased latency period and increase in percentage of time spent in the target quadrant. Administration of TSA also improved antioxidant activities by increased T-SOD, GSH, and decreased MDA activities compared to lead-treated group. CONCLUSION: This study provides evidence of that TSA has a neuroprotective effect against lead-induced cognitive deficit by enhancing antioxidant activities in the brain (Tab. 2, Fig. 3, Ref. 27).

Effects of Zinc and N-Acetylcysteine in Damage Caused by Lead Exposure in Young Rats.

This study investigated the toxicity of rats exposed to lead acetate (AcPb) during the second phase of brain development (8-12 days postnatal) in hematological and cerebral parameters. Moreover, the preventive effect of zinc chloride (ZnCl2) and N-acetylcysteine (NAC) was investigated. Pups were injected subcutaneously with saline (0.9% NaCl solution), ZnCl2 (27 mg/kg/day), NAC (5 mg/kg/day) or ZnCl2 plus NAC for 5 days (3rd-7th postnatal days), and with saline (0.9% NaCl solution) or AcPb (7 mg/kg/day) in the five subsequent days (8th-12th postnatal days). Animals were sacrificed 21 days after the last AcPb exposure. Pups exposed to AcPb presented inhibition of blood porphobilinogen-synthase (PBG-synthase) activity without changes in hemoglobin content. ZnCl2 pre-exposure partially prevented PBG-synthase inhibition. Regarding neurotoxicity biomarkers, animals exposed to AcPb presented a decrease in cerebrum acetylcholinesterase (AChE) activity and an increase in Pb accumulation in blood and cerebrum. These changes were prevented by pre-treatment with ZnCl2, NAC, and ZnCl2 plus NAC. AcPb exposure caused no alteration in behavioral tasks. In short, results show that AcPb inhibited the activity of two important enzymatic biomarkers up to 21 days after the end of the exposure. Moreover, ZnCl2 and NAC prevented the alterations induced by AcPb.

Honey prevents neurobehavioural deficit and oxidative stress induced by lead acetate exposure in male Wistar rats- a preliminary study.

This research sought to investigate the possible neuroprotective effects of honey against lead (Pb)-induced neurotoxicity. Twenty four male Wistar rats were divided into four groups: Control group that received 1 ml/kg distilled orally for 28 days; while groups II-IV received 0.2% lead in drinking water and 1 ml/kg of distilled water, 1 ml/kg of honey, 1.5 ml/kg of honey respectively for 28 days. Anxiety and exploratory activities were determined in the open field test. Memory function was determined using Morris water maze after which the animals were sacrificed. The brains were then excised, homogenized and Lipid peroxidation (MDA), Superoxide dismutase (SOD), Catalase, Glutathione (GSH) and Glutathione -S- Transferase (GST) activities were determined in the brains. Results showed that lead exposure causes decrease in locomotor and exploratory activities; increase anxiety, memory impairment, lipid peroxidation and decrease antioxidant activities. However, co-administration of honey with lead inhibited neurotoxicity as indicated by the improvement in memory function as evidenced by decreased latency period and increased in time spent in target quadrant in honey-fed rats compared to the lead-exposed animals. Furthermore, honey increased locomotion, exploration and decreased anxiety in lead-exposed rats as indicated by the frequency of rearing, freezing duration and the number of line crossed by animals. Also administration of honey improves antioxidant activities as shown by increased brain SOD, GST and GSH activities compared to the lead-treated groups but no significant effect on MDA level. It can be concluded that honey has neuroprotective effects against lead-induced cognitive deficit probably by enhancing antioxidant activities.

Attenuation of lead neurotoxicity by supplementation of polyunsaturated fatty acid in Wistar rats.

BACKGROUND: Among various types of polyunsaturated fatty acid (PUFA), omega-3 fatty acids play a crucial role in development and function of the brain. This study was undertaken to investigate the possible neuroprotective efficacy of omega-3 fatty acid on lead-induced neurotoxicity in rats. MATERIAL AND METHODS: The experiment was carried out on 32 male Wistar rats divided into four groups. The first group (control) was treated with distilled water and second group with lead acetate at the doses of 3 mg/kg b.wt. (body weight)/oral, whereas third and fourth groups were simultaneously treated with lead acetate (3 mg/kg b.wt.) plus omega-3 fatty acid (300 mg/kg b.wt./oral) and lead acetate (3 mg/kg b.wt.) plus vitamin E (100 mg/kg b.wt./oral), respectively, for a period of 90 days. Their biochemical and histopathological investigations have been carried out. RESULTS: The level of lead was markedly elevated in brain (4.71-fold) and blood (5.65-fold), also increased levels of ROS, GSH, LPO with concomitant reduction in the activities of delta-ALAD, CAT, SOD, and GPx. In addition, lead-induced brain damage was indicated by histopathological changes. Omega-3 fatty acid resulted in marked improvement in most of the biochemical parameters as well as histopathological changes in rats. The results obtained were compared with vitamin E as the standard antioxidant agents. DISCUSSION: Omega-3 fatty acid significantly (P < 0.05) decreased the effect of lead-induced brain damage as well as biochemical changes similar to that of standard drug, vitamin E. So, our result suggested that omega-3 fatty acid may play a protective role in lead-induced neurotoxicity and associated human health risk.

Potential of casein as a nutrient intervention to alleviate lead (Pb) acetate-mediated oxidative stress and neurotoxicity: First evidence in Drosophila melanogaster.

Understanding the interaction between dietary protein deficits and neurotoxicants such as lead (Pb) is critical since oxidative stress is a common denominator under such conditions. The Drosophila system is an extensively used model to investigate the interaction between nutrients and environmental toxicants. Accordingly, we have examined the hypothesis that casein (CSN) enrichment has the propensity to attenuate Pb-associated phenotype, oxidative stress and neurotoxicity in Drosophila melanogaster. Exposure of young (2-3 d) and adult flies (10-12 d old) to Pb acetate (0-20 mM, 7 d) in the medium resulted in a concentration dependent mortality and the survivors exhibited a hyperactive phenotype. While males showed higher susceptibility to Pb among both age groups, young flies were relatively more susceptible than adults. Pb exposure (5-10 mM, 5 d) among young flies caused robust oxidative stress as evidenced by markedly elevated levels of reactive oxygen species with concomitant perturbations in the activities of antioxidant enzymes (diminished SOD and elevated thioredoxin reductase) and altered redox state. Further, Pb caused significant elevation in the activity of acetylcholinesterase and dopamine levels. In a satellite study, we assessed the modulatory effect of CSN-enriched diet (1-2%) on Pb intoxication in terms of lethality, hyperactivity, oxidative stress and neurotoxicity. CSN markedly offset Pb-induced lethality and diminished the hyperactivity response. While CSN enrichment among Pb (5 mM) treated flies caused further elevation in ROS levels and thioredoxin reductase activity, the SOD levels were restored to normalcy. Further, CSN improved the activity levels of complex I-III and restored the dopamine levels. Our data suggest that Pb-induced toxicity in the Drosophila system may be predominantly mediated through oxidative stress mechanisms and the propensity of casein-enriched diet to abrogate such responses. Hence, we propose that enrichment of diet with protein such as casein may be a useful approach to alleviate Pb associated adverse effects in children.

The protective effect of green tea extract on lead induced oxidative and DNA damage on rat brain.

The role of green tea in protection against neurotoxicity induced by lead acetate was investigated in rats. Five equal groups, each of ten rats were used. The first group was served as control, the second, third, and fourth groups were given lead acetate, lead acetate and green tea, and green tea only, respectively, for one month, the fifth group was administered lead acetate for one month followed by green tea for 15 days. Lead acetate was given orally at a dose of 100 mg/kg b. wt, while green tea was given in drinking water at a concentration of 5 g/L. Lead acetate administration induced loss of body weight and decreased concentration of reduced glutathione and SOD activity in brain tissues as well as significantly high DNA fragmentation and pathological changes. Co-administration of green tea with lead acetate significantly alleviated these adverse effects.

Effects of flaxseed oil on lead acetate-induced neurotoxicity in rats.

It is well known that chronic exposure to lead (Pb(+2)) alters a variety of behavioral tasks in rats and mice. Here, we investigated the effect of flaxseed oil (1,000 mg/kg) on lead acetate (20 mg/kg)-induced brain oxidative stress and neurotoxicity in rats. The levels of Pb(+2), lipid peroxidation, nitric oxide (NO), and reduced glutathione (GSH) and the activity of catalase (CAT), superoxide dismutase (SOD), glutathione reductase (GR), glutathione-S-transferase (GST), and glutathione peroxidase (GPx) were determined in adult male albino rats. The level of Pb(+2) was markedly elevated in brain and blood of rats. This leads to enhancement of lipid peroxidation and NO production in brain with concomitant reduction in GSH, CAT, SOD, GR, GST, and GPx activities. These findings were associated with DNA fragmentation. In addition, lead acetate induced brain injury as indicated by histopathological changes of the brain. Treatment of rats with flaxseed oil resulted in marked improvement in most of the studied parameters as well as histopathological features. These findings suggest to the conclusion that flaxseed oil significantly decreased the adverse harmful effects of lead acetate exposure on the brain as well as Pb(+2)-induced oxidative stress.

Locomotor damage and brain oxidative stress induced by lead exposure are attenuated by gallic acid treatment.

We investigated the antioxidant potential of gallic acid (GA), a natural compound found in vegetal sources, on the motor and oxidative damages induced by lead. Rats exposed to lead (50 mg/kg, i.p., once a day, 5 days) were treated with GA (13.5mg/kg, p.o.) or EDTA (110 mg/kg, i.p.) daily, for 3 days. Lead exposure decreased the locomotor and exploratory activities, reduced blood ALA-D activity, and increased brain catalase (CAT) activity without altering other antioxidant defenses. Brain oxidative stress (OS) estimated by lipid peroxidation (TBARS) and protein carbonyl were increased by lead. GA reversed the motor behavior parameters, the ALA-D activity, as well as the markers of OS changed by lead exposure. CAT activity remained high, possibly as a compensatory mechanism to eliminate hydroperoxides during lead poisoning. EDTA, a conventional chelating agent, was not beneficial on the lead-induced motor behavior and oxidative damages. Both GA (less) and EDTA (more) reduced the lead accumulation in brain tissue. Negative correlations were observed between the behavioral parameters and lipid peroxidation and the lead levels in brain tissue. In conclusion, GA may be an adjuvant in lead exposure, mainly by its antioxidant properties against the motor and oxidative damages resulting from such poisoning.

Selection of nutrients for prevention or amelioration of lead-induced learning and memory impairment in rats.

BACKGROUND: We carried out animal experiments based on the orthogonal design L(8)(2(7)) setting seven factors with two different levels of each and 10 groups of rats. The nutrients tested were tyrosine, glycine, methionine, taurine, ascorbic acid, thiamine and zinc. OBJECTIVES: The objective of this study was to explore the optimal combinations of nutrients for prevention or amelioration of lead-induced learning and memory impairment. METHODS: Rats were supplemented with nutrients by gavage once a day in two experiments: one was simultaneous nutrient supplementation with lead acetate administration (800 mg l(-1)) for 8 weeks (prophylactic supplementation) and the other was nutrient supplementation for 4 weeks after the cessation of 4 weeks of lead administration (remedial supplementation). Morris water maze was initiated at ninth week. Rats were terminated for assays of levels of Pb in blood, activities of superoxide dismutase (SOD) and nitric oxide synthase (NOS) in hippocampus, levels of nitric oxide (NO) in hippocampus and expressions of Ca2+/calmodulin-dependent protein kinase II (CaMKII) and cyclic adenosine monophosphate (cAMP) response element-binding protein messenger RNA in hippocampus. RESULTS: Results showed that in prophylactic supplementation, methionine, taurine, zinc, ascorbic acid and glycine were the effective preventive factors for decreasing prolonged escape latency, increasing SOD and NOS activities and NO levels in the hippocampus, respectively. On the other hand, in remedial supplementation, taurine was the effective factor for reversing Pb-induced decrease in activities of SOD, NOS and levels of NO. CONCLUSIONS: In conclusion, the optimum combinations of nutrients appear to be methionine, taurine, zinc, ascorbic acid and glycine for the prevention of learning and memory impairment, while taurine and thiamine appear to be the effective factors for reversing Pb neurotoxicity.

Monosialoanglioside (GM1) prevents lead-induced neurotoxicity on long-term potentiation, SOD activity, MDA levels, and intracellular calcium levels of hippocampus in rats.

Lead (Pb(2+)) is one of the most common neurotoxic metals present in our environment. Chronic or acute exposure to Pb(2+) causes impairment to the central nervous system (CNS). As one potent useful tool in the attempt to protect against impairment and promote functional recovery of the CNS, gangliosides are hopeful for recovering Pb(2+) neurotoxicity. The aim of this study is to investigate the effects of monosialoganglioside (GM1) on the Pb(2+)-induced impairments of synaptic plasticity, antioxidant system function, and intracellular calcium levels in the hippocampus of acute Pb(2+)-exposed rats. Our study showed that: (1) Acute Pb(2+) exposure impaired synaptic transmission and plasticity in the hippocampus and GM1 preconditioning rescued to some extent this impairment in urethane-anesthetized rats. (2) Superoxide dismutase activities and malondialdehyde levels were significantly increased in the acute Pb(2+)-exposed hippocampus which could be reduced by GM1 preconditioning. (3) Further, acute Pb(2+) exposure caused the internal free Ca(2+) fluctuation in the cultured hippocampal neurons and GM1 preconditioning could abate this fluctuation. Taken together, our results illustrated the possible mechanisms underlying the protective effects of GM1 against Pb(2+) neurotoxicity and might shed light on protection against Pb(2+) toxicity and its treatment.

Protective antioxidant effect of Centella asiatica bioflavonoids on lead acetate induced neurotoxicity.

Lead (Pb) is a neurotoxic heavy metal and children in the developmental stage are particularly susceptible to toxic effects of lead exposure. The brain is the key organ involved in interpreting and responding to potential stressors. Epidemiological investigations have established the relationship between chronic lead exposure and cognitive impairments in young children. Excessive production of radical species plays an important role in neuronal pathology resulting from excitotoxic insults, therefore one plausible neuroprotective mechanism of bioflavonoids is partly relevant to their metal chelating and antioxidant properties. Centella asiatica (CA) is a tropical medicinal plant enriched with bioflavonoids and triterpenes and selenium, reported to rejuvenate the cells and promote physical and mental health. Bioflavonoids are claimed to be exert antimutagenic, neurotrophic and xenobiotics ameliorating and membrane molecular stabilizing effects. The objective of the present work is to study the protective antioxidant effect of pretreatment of CA extract (CAE) on lead acetate induced changes in oxidative biomarkers in the central nervous system (CNS) of mice.

Protective effects of Hippophae rhamnoides L. juice on lead-induced neurotoxicity in mice.

We examined the effect of Hippophae rhamnoides L. (HRL) juice on lead-induced memory impairment and neuronal damage in the brains of adult mice. Kunming mice were exposed to lead acetate 10 mg/kg body weight for 20 d. Twenty percent and 40% HRL prevented the lead-induced decrease in step-through latency. In the water maze test, the swimming time was lengthened in mice treated with lead acetate, but this time was decreased in mice that received 20% and 40% HRL. The malondialdehyde (MDA) levels were increased in lead-treated mice, which were reduced by 20% and 40% HRL in dose-dependent manner. The activities of acetylcholinesterase (AchE) and monoamine oxidase-A and -B were significantly increased in the lead-treated group, which were decreased by 40% HRL but not by 20% HRL. The levels of norepinephrine, serotonin, and 5-hydroxyindole acetic acid were decreased significantly in the lead-treated mice, and the decreases were antagonized by 40% HRL, except for than in dopamine, but 20% HRL had no effect on this change. These data suggest that the different doses of the HRL juice protect against the lead acetate-induced deficits in learning and memory and changes in neurobiochemical parameters.

Zinc and calcium reduce lead induced perturbations in the aminergic system of developing brain.

Since alterations in monoamines and monoamine oxidase (MAO) have been postulated to play a role in toxic effects of lead (Pb) on the central nervous system, we have examined the protective effects of calcium (Ca2+) and zinc (Zn2+) supplementation on Pb-induced perturbations in the levels of monoamines and the activity of MAO. Swiss albino mice were lactationally exposed to low (0.2%) and high (1%) levels of Pb-acetate via drinking water of the mother. Pb-exposure commenced on postnatal day (PND) 1, continued up to PND 21 and stopped at weaning. Ca2+ or Zn2+ (0.02% in 0.2% Pb-water or 0.1% in 1% Pb-water) was supplemented separately to the mother up to PND 21. The levels of monoamines (epinephrine, norepinephrine, dopamine and serotonin) and the activity of MAO in the brain regions such as hippocampus, cortex, cerebellum and medulla of young (1 month old) and adult (3 month old) mice were determined in the synaptosomal fractions. The synaptosomal monoamines though increased with low level (0.2%) Pb-exposure, significantly decreased with high level (1%) Pb-exposure in all the brain regions in both the age groups. In general, the young mice seem to be more vulnerable to Pb-neurotoxicity. Ca2+ or Zn2+ supplementation significantly reversed the Pb-induced perturbations both in the levels of monoamines and in the activity of MAO. However, the recovery in monoamine levels and MAO activity was more pronounced with Ca2+ supplementation as compared to Zn2+. These results provide evidence that dietary Ca2+ and/or Zn2+ provide protection against Pb-induced neurotoxic effects.