Lead-treated Animals Research Articles

Cabbage (Brassica oleracea) mitigates lead (II) acetate-induced testicular dysfunction in Wistar rats via up-regulation of Bcl-2 protein expression, pituitary-testicular hormonal axis and down-regulation of oxido-inflammatory reactions.

Oxido-inflammatory stress has been involved in lead-induced testicular dysfunction and plants rich in anti-oxidants has been reported to be beneficial in combating heavy metal poisonings in animal studies. However, cabbage juice protective effect on lead-induced testicular dysfunction was investigated in this study. Twenty male Wistar rats were selected into four (n=5) groups and given distilled water (1ml/100 g body weight), lead acetate (25 mg/kg body weight), cabbage juice (1 ml/100 g body weight), and lead acetate with cabbage juice, respectively. All treatments were administered orally for 28 days. Sperm count, motility, viability, testosterone, luteinising hormone and follicle-stimulating hormone, testicular Bcl-2 expression, and enzymatic anti-oxidant capabilities were considerably (p < 0.05) decrease in lead-treated animals. However, cabbage juice significantly (p < 0.05) elevated these parameters. Testicular malondialdehyde, tumour necrosis factor-α, nitric oxide and interleukin-6 was elevated by lead acetate. When comparing cabbage juice-treated animals to lead-treated animals, all of these parameters were considerably (p < 0.05) downregulated in cabbage juice-treated animals. Following lead administration, the testes' histomorphological alterations were not totally recovered despite therapy with cabbage juice. Conclusively, this study suggest that cabbage juice mitigates testicular dysfunction associated with lead exposure via its anti-oxidant, anti-inflammatory, anti-apoptotic and androgenic properties.

Effect of Emblica officinalis fruits against metallic-lead induced biochemical and hematological alterations in Wistar rats

Lead toxicity and related health issues have become global concern due to increased use of lead-based products in the modern world. Though attempts are being made to tackle this malady through many ways, the use of naturally occurring materials that are available locally is a subtle approach. In this investigation, the fruits of E. officinalis (EO) were studied for their potential in overcoming biochemical and hematological alterations caused by metallic lead in rat model. Four groups of rats, each containing six animals, were considered for the study. Group I served as normal control while to other groups (II– IV), metallic lead powder (100 ppm/rat) was orally administrated for 30 consecutive days. From day 31, the animals in groups III and IV were treated with EO in doses of 50 and 100 mg/kg body weight (p. o.), respectively, for the following seven days. Group II served as lead-treated control. On day 38, the animals in all groups were sacrificed and the blood was collected and serum separated. The changes in biochemical (aspartate aminotrasferase, alanine aminotrasferase, alkaline phosphatase, gamma glutamyltrasferase, total cholesterol, triglycerides, urea, creatinine and calcium) and hematological (red blood cell count, white blood cell count, hemoglobin, packed cell volume and platelet count) parameters were estimated. Lead treated animals in Group - II showed appreciable changes in hematological and biochemical parameters. Treatment with EO (50 and 100 mg/kg) significantly restored the changes in the above parameters to near normal values implying that the fruit of E. officinalis is an effective natural material to overcome widespread lead toxicity. This observation is further supported by histopathological studies of liver and kidney tissues wherein the distorted architecture, degeneration and other changes found in lead-treated animals were brought back to near normal stages by the treatment of EO.

Protective effect of Abutilon indicum against lead-induced reproductive toxicity in male Wistar rats.

Despite ample literature on the toxic impact of lead on the environment and health, the exact mechanism of pathogenesis/toxicity is not clearly known. Because it is well established that lead induces oxidative stress, it is assumed that exposure to antioxidants may reduce the toxic impact of lead. In this study, we evaluated the impact of coadministration of the methanolic root extract of a plant Abutilon indicum (50, 100, 200 mg kg -1 b.wt.) in mitigating the toxic impact of lead on the reproductive system of rats. In brief, Wistar rats were exposed to lead acetate in drinking water with or without coadministration of plant root extract and compared with that of control animals. After 45 days of exposure as outlined above, the animals were killed and the reproductive toxicity was assessed by sperm parameters, hormone and antioxidant enzyme assays, and testis histopathology. Significant reduction in testis weight, sperm count, testosterone levels, and antioxidant enzymes levels such as Superoxide Dismutase, Catalase, and Glutathione peroxidase was seen in lead-treated animals, confirming the toxic impact. The coadministration of A. Indicum (100 and 200 mg kg -1 b.wt.) was found to bring the studied parameters close to the levels seen in untreated (control) animals. Our findings are indicative of the protective nature of A. Indicum against lead-induced reproductive toxicity in a dose-dependent manner. However, further characterization of the root extract is required to elucidate the probable mechanism of protection.

Gene-environment interaction between lead and Apolipoprotein E4 causes cognitive behavior deficits in mice

BackgroundAlzheimer’s disease (AD) is characterized by progressive cognitive decline and memory loss. Environmental factors and gene-environment interactions (GXE) may increase AD risk, accelerate cognitive decline, and impair learning and memory. However, there is currently little direct evidence supporting this hypothesis.MethodsIn this study, we assessed for a GXE between lead and ApoE4 on cognitive behavior using transgenic knock-in (KI) mice that express the human Apolipoprotein E4 allele (ApoE4-KI) or Apolipoprotein E3 allele (ApoE3-KI). We exposed 8-week-old male and female ApoE3-KI and ApoE4-KI mice to 0.2% lead acetate via drinking water for 12 weeks and assessed for cognitive behavior deficits during and after the lead exposure. In addition, we exposed a second (cellular) cohort of animals to lead and assessed for changes in adult hippocampal neurogenesis as a potential underlying mechanism for lead-induced learning and memory deficits.ResultsIn the behavior cohort, we found that lead reduced contextual fear memory in all animals; however, this decrease was greatest and statistically significant only in lead-treated ApoE4-KI females. Similarly, only lead-treated ApoE4-KI females exhibited a significant decrease in spontaneous alternation in the T-maze. Furthermore, all lead-treated animals developed persistent spatial working memory deficits in the novel object location test, and this deficit manifested earlier in ApoE4-KI mice, with female ApoE4-KI mice exhibiting the earliest deficit onset. In the cellular cohort, we observed that the maturation, differentiation, and dendritic development of adult-born neurons in the hippocampus was selectively impaired in lead-treated female ApoE4-KI mice.ConclusionsThese data suggest that GXE between ApoE4 and lead exposure may contribute to cognitive impairment and that impaired adult hippocampal neurogenesis may contribute to these deficits in cognitive behavior. Together, these data suggest a role for GXE and sex differences in AD risk.

Lead Toxicity and The Hypothalamic-Pituitary-Testicular Axis

Environmental exposure to toxic levels of lead (Pb) occurs in a number of industries with potential adverse effects on the reproductive capacity of exposed men. Clinical and animal studies indicate that abnormalities of spermatogenesis result from toxic lead exposure, but eventual histopathologic alterations involved have not been identified. To explore putative abnormalities in the reproductive gonadotropic axis following lead intoxication, experimental animals when exposed to low levels of lead, 65 days old animals were treated with distilled water containing 0, 0 mg (control), 10 mg lead (Pb)/Kg/day and 15 mg lead (Pb)/Kg/day intraperitoneally for 20 days. At the end of treatment, the animals were sacrificed and the blood collected for luteinizing hormone (LH) and testosterone assays. The testis was processed for histological analysis. The results showed a high serum concentration of LH and testosterone in lead-treated animals compared to controls. Histological examination of testis showed deformities in testicular morphology of lead intoxicated animals with gross damage within the somniferous tubules. A strong correlation was established between LH and testosterone suggesting an alteration in the endocrine components of the gonadotropic axis. Histological examination of pituitary gland showed some degenerative changes in endocrine cells of lead group. Changes in LH and testosterone levels suggest that Pb exposure during the critical time of sexual differentiation induces reproductive axis abnormalities in adulthood. In conclusion, lead has a gonadotoxic effect by decreasing LH and testosterone levels and damaging the testis seminiferous tubules. Catalase activity was significantly reduced in the lead group following 65 days of exposure which possibly indicates that lead might had other mechanisms of action, such as increasing oxidative damage.

Biochemical effects of gestational coexposure to lead and cadmium on reproductive performance, placenta, and ovary

Adult virgin 4-day cycling synchronized Charles foster females were treated subcutaneously (0.05 mg/kg body wt/day) with sodium acetate (control), lead acetate or cadmium acetate alone, or both during gestational period, with pretreatment of 5 days prior to mating. There were no alterations in reproductive performance in all metal-treated groups. Implantation enzymes, cathepsin-D and alkaline phosphatase, activity were altered, but no change in the reproductive performance was observed. The key steroidogenic enzymes of ovary and placenta (3beta-HSD and 17beta-HSD), along with gonadal steroids, were affected the most in cadmium and combined treated animals whereas lead-treated animals showed a minimum change compared to the control group. Maximum displacement of zinc bound to metallothionein was more in cadmium and combined treated rats when compared to other metal-treated groups. Biomolecules such as glycogen, protein, RNA, DNA, and protein content were affected in all metal-treated groups, whereas cadmium-treated animals showed greater effect. General parameters of toxicity such as alkaline phosphatase, serum glutamate pyruvate transaminase, and creatinine were altered but were within the normal range. Biochemical effects are correlated with metals accumulated in blood, reproductive tissue such as placenta and ovary.

Hepatoprotective Role of Zinc in Lead-Treated, Protein-Deficient Rats

The current study was designed to evaluate the hepatoprotective role of zinc after lead (Pb) treatment of protein-deficient (PD) rats. The animals were subjected to seven different treatment groups: G-1 (normal control, 18% protein), G-2 (protein-deficient, 8% protein), G-3 (Pb-treated, 100 mg/kg body weight of lead acetate), G-4 (Zn-treated, zinc sulfate at a dose level of 227 mg/L drinking water), G-5 (PD + Pb-treated), G-6 (PD + Zn-treated), and G-7 (PD + Pb + Zn-treated). Serum albumin levels and total serum protein contents were estimated to assess the severity of protein deficiency at the end of 8 weeks in all the treatment groups. Also, the study explored the role of zinc on antioxidative defense system enzymes in liver of protein-deficient rats subjected to lead toxicity treatment. Further, the study was extended to elucidate the levels of zinc and lead in liver tissue after different treatments of rats using positron-induced X-ray emission technique (PIXE). The current study indicated a significant change in the levels of various antioxidative enzymes and serum albumin as well as total protein contents of protein-deficient rats subjected to lead treatment. A significant increase in the levels of malondialdehyde (MDA), catalase, and glutathione peroxidase (GPx) was seen after 8 weeks of lead treatment of protein-deficient rats. On the contrary, levels of albumin, total protein content, superoxide dismutase (SOD), GSH, were found to be decreased. Interestingly, zinc supplementation has tended to normalize the altered levels of these enzymes to a significant extent. The levels of zinc in liver tissue was found to be decreased significantly in protein-deficient as well as lead-treated rats. However, hepatic zinc concentration was increased to a significant extent in protein-deficient rats supplemented with zinc when compared with protein-deficient rats. Further, the presence of lead was also observed in livers of lead-treated animals. In conclusion, the study revealed the antioxidative role of zinc in hepatotoxic conditions induced by subjecting the rats to protein-deficient diet and lead treatment.

Postnatal Inorganic Lead Exposure Reduces Midbrain Dopaminergic Impulse Flow and Decreases Dopamine D1 Receptor Sensitivity in Nucleus Accumbens Neurons

Lead treatment via drinking water for 3 to 6 weeks at 250 ppm was found to significantly decrease the number of spontaneously active dopamine (DA) neurons in both the substantia nigra and ventral tegmental area that were recorded using standard extracellular electrophysiological recording techniques. Lead exposure did not affect the discharge rate or discharge pattern of these DA neurons. No significant decrease in the number of tyrosine hydroxylase immunopositive cells was detected in lead-treated animals relative to controls even though the length of lead exposure was extended beyond that of the electrophysiological studies. The significant lead-induced decrease in spontaneously active cells observed in the electrophysiological studies was, therefore, not due to cell death. An acute drug challenge with the DA receptor agonist apomorphine at a dose known to hyperpolarize midbrain DA neurons (50 mug/kg i.v.) was used to determine whether hyperpolarization would normalize the number of spontaneously active DA neurons. The results suggest that depolarization inactivation was most likely not the cause for this lead effect. The D(1) receptor agonist SKF-38393 [1-phenyl-2,3,4,5-tetrahydro-(1H)-3-benzazepine-7,8-diol] was iontophoretically applied to type I nucleus accumbens (Nacb) neurons. The results demonstrated that type I Nacb neurons have a significantly lower basal discharge rate in lead-treated animals relative to controls and that the Nacb DA D(1) receptors were significantly less sensitive to SKF-38393 in the lead-treated animals. Therefore, lead exposure decreases DA neuron impulse flow presynaptically and decreases DA D(1) receptor sensitivity postsynaptically in the nucleus accumbens.

Investigation of circulatory and tissue ACE activity during development of lead-induced hypertension

Prolonged exposure to low levels of lead causes systemic hypertension. Several mechanisms have been proposed to explain lead-induced hypertension. Recently, the etiological role of the renin–angiotensin system (RAS) has been investigated in this context. This study assessed the alterations of circulatory and tissue angiotensin converting enzyme (ACE) activity during development of lead induced hypertension. Male rats were divided to two main groups: lead-treated animals which received lead acetate, 100 ppm, in drinking water for 2, 4, 6, and 8 weeks and a control group given distilled water. The ACE activity in serum and tissues was analyzed by HPLC. The blood pressure gradually increased in correlation with lead exposure with time. The study also revealed significant elevation of local and serum ACE activity in the early phase of lead treatment; however, chronic lead exposure suppressed ACE activity in serum and tissues. These results emphasize the etiological role of ACE activity in the early phase of lead-induced hypertension.

Lead stimulates ERK1/2 and p38 MAPK phosphorylation in the hippocampus of immature rats

Lead (Pb 2+) is widely recognized as a neurotoxicant whose mechanisms of action are not completely established. We have previously demonstrated that Pb 2+ can activate the p38 MAPK pathway and increase the phosphorylation of Hsp27 in bovine adrenal chromaffin cells and human SH SY5Y cells over a short incubation period (1 h). In the present work we analyzed the effects of Pb 2+ administered in vivo on the level and the phosphorylation state of ERK1/2 and p38 MAPK in the hippocampus of immature rats. Rats were treated with lead acetate (2, 8 or 12 mg/kg, i.p.) or saline (control) over the 8th to 12th postnatal days, and hippocampal slices were prepared on the14th day. The Pb 2+ level in the lead-treated animals increased 2.5–6-fold in the blood (3.0–6.0 μg/dl) and 2.0–3.0-fold in the forebrain (78–103 ng/g wet weight), compared to control (saline). The phosphorylation of both ERK1/2 and p38 MAPK was significantly increased by prior exposure to Pb 2+ in vivo. In in vitro experiments, hippocampal slices from 14-day-old rats were exposed to Pb 2+ (1–10 μM) for 1 and 3 h. There were no changes in the phosphorylation state of ERK and p38 MAPK for 1-h incubation, whereas a significant increase of ERK1/2 and p38 MAPK phosphorylation by Pb 2+ (5 μM) was observed for the 3-h incubation. Cell viability measured using MTT was not modified in any of the conditions tested. These results indicate that the phosphorylation of hippocampal ERK1/2 and p38 MAPK is stimulated by lead in a period of rapid brain development, an effect that may underlie, at least in part, the neurotoxicty elicited by this metal.

Ca2+/calmodulin-mediated neurotransmitter release and neurobehavioural deficits following lead exposure.

The present study was designed to investigate the effect of in vitro and in vivo lead exposure on calmodulin-mediated neurotransmitter release from synaptic vesicles with a view to explain the mechanism involved in its behavioural effects. It was observed that lead stimulated calmodulin, in terms of its ability to activate cAMP phosphodiesterase, following in vitro and in vivo exposure. Lead was also seen to enhance calmodulin-mediated synaptic vesicle protein phosphorylation. The increase in lead-induced synaptic vesicle protein phosphorylation was accompanied by enhanced release of acetylcholine from synaptic vesicles following in vitro lead exposure by a calmodulin-dependent mechanism. The ability of Ca(2+)/calmodulin to evoke acetylcholine release was reduced in the synaptic vesicles isolated from lead-exposed animals. Concomitantly, the levels of acetylcholine were found to decrease by 37.8% in the lead-treated animals as compared to the controls. The neurochemical alterations following lead exposure were accompanied by neurobehavioural deficits in terms of impaired motor and cognitive functions. The results from the present study clearly suggest that lead exerts its neurotoxic effects by interfering with Ca(2+)/calmodulin-mediated neurotransmitter release that is eventually responsible for behavioural impairment.

Influence of brain catalase on ethanol-induced loss of righting reflex in mice

The effect of lead acetate and 3-amino-1, 2, 4-triazole (AT) on ethanol-induced loss of righting reflex (LORR) and brain catalase activity was studied in an attempt to confirm earlier observations on the involvement of catalase in ethanol-induced effects. Lead acetate (0 or 100 mg/kg) or AT (0 or 500 mg/kg) was injected (acutely) into mice 7 days or 5 h before testing. Other mice were exposed to drinking fluid containing 500 ppm lead acetate for 60 days. On the test day, mice received an intraperitoneal injection of ethanol (4.0 or 4.5 g/kg) and the duration of LORR was recorded. Acute lead-treated animals demonstrated a reduction in the duration of the LORR. However, both chronic administration of lead acetate and AT treatment increased the duration of ethanol-produced LORR. Furthermore, brain catalase activity in acute lead pretreated animals showed a significant induction, whereas it was reduced in chronic lead and AT treated mice. These results suggest that brain catalase activity, and by implication centrally formed acetaldehyde, may modulate ethanol-induced LORR.

Lead exposure activates nuclear factor kappa B, activator protein-1, c-Jun N-terminal kinase and caspases in the rat brain

How lead manifests its neurotoxicity is not well understood. The hypothesis that lead may activate nuclear transcription factors NF-κB, activator protein-1 (AP-1), c-Jun N-terminal kinase (JNK), mitogen-activated protein kinase kinase (MAPKK) and caspases in the rat brain leading to the manifestation of its neurotoxic effects, was tested in 21-day-old male Long–Evans rats exposed to 50 ppm Pb in drinking water for 90 days. After the 90-day exposure, blood lead levels of the rats in control group were 4±0.2 μg/dl, while those of the Pb-exposed group were 18±0.3 μg/dl ( n=50). Similarly, at the end of the exposure period, the Pb-exposed group showed significantly higher accumulation of Pb in brain regions such as, frontal cortex (FC), brain stem (BS), striatum (ST), and hippocampus (HIP) (338.6±7.7, 391.6±3.8, 288.3±6.7, and 382.3±3.3 ng/g wet tissue, respectively, in FC, BS, ST, and HIP) than the control group (126.6±2.7, 127.6±1.8, 201.3±9.4, and 180.3±4.4 ng/g wet tissue, respectively, in FC, BS, ST, and HIP). There was a 3–4-fold increase in NF-κB and AP-1 level in all the four regions of the brain of lead-treated animals. All four regions showed 4–10-fold activation of JNK and a 5–6-fold activation of MAPKK. As indicated by poly(ADP ribose) polymerase cleavage, lead exposure induced the activation of caspases in all four regions. Overall our results indicate that lead exposure induces the activation of NF-κB, AP-1, JNK, MAPKK, and caspases in the brain, which may contribute to its neurotoxic effects.

Skeletal effects of developmental lead exposure in rats.

To identify possible direct and indirect mechanisms underlying the effects of lead on skeletal growth, 3 studies were conducted. In the first study, 1 male and 1 female pup/litter (n = 5 litters), were exposed ad libitum to 0, 825, or 2475 ppm lead acetate in the drinking water from gestational day 4 to euthanasia on day 55. Tibial strength was tested by 3-point bending and plasma levels of vitamin D metabolites were measured. A dose-dependent decrease of the load to failure was demonstrated but only in male pups. No differences in plasma levels of vitamin D metabolites were observed. In the second study, conducted to test if hormone treatment would attenuate the lead deficits, male and female pups were exposed to 0 or 2475 ppm lead acetate and then, from 30-60 days of age, received either saline vehicle, L-dopa, testosterone (males only), dihydrotestosterone (DHT, males only), or estradiol (females only). Lead exposure significantly reduced somatic growth, longitudinal bone growth, and bone strength during the pubertal period. Sex steroid replacement did not restore skeletal parameters in lead-exposed rats. L-Dopa increased plasma insulin-like growth factor 1 (IGF(1)) concentrations, rates of bone growth, and bone strength measures in controls while having no effect in lead-exposed pups. The third study was conducted at 100 days of age, when endocrine parameters have been shown to be normalized, to test for effects of lead exposure on bone formation during tibial limb lengthening (distraction osteogenesis, DO). Both DO gap x-ray density and proximal new endosteal bone formation were decreased in the distraction gaps of the lead-treated animals (p < 0.01). In conclusion, lead exposure reduced somatic growth, longitudinal bone growth, and bone strength during the pubertal period, and these effects could not be reversed by a growth hormone (GH) axis stimulator or by sex-appropriate hormones. Finally, lead exposure appears to specifically inhibit osteoblastogenesis in vivo in adult animals.

Serum levels of TCDD and dioxin-like chemicals in Rhesus monkeys chronically exposed to dioxin: correlation of increased serum PCB levels with endometriosis.

Humans and animals are exposed daily to a complex mixture of polyhalogenated aromatic hydrocarbons (PHAHs). Previous work has shown that exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is associated with a dose-dependent increase in the incidence and severity of endometriosis in the rhesus monkey. Dioxin-like chemicals can also exert effects in combination with TCDD via the aryl hydrocarbon receptor. This study demonstrates that the serum levels of TCDD and specific dioxin-like PHAH congeners were increased in TCDD-treated animals with endometriosis 13 years after the TCDD exposure. Nine TCDD-exposed and 6 unexposed female rhesus monkeys were evaluated for serum content of relevant compounds and for endometriosis by surgical laparoscopy. Additional studies were done on 4 animals that died 7 to 11 years after exposure to TCDD and 4 lead-treated animals with no history of PHAH treatment. For TCDD-exposed and unexposed animals, TCDD exposure correlated with an increased serum TCDD concentration. Furthermore, TCDD exposure and an elevated serum TCDD concentration were associated with increased serum levels of triglycerides, 1,2,3,6,7,8-hexachlorodibenzofuran, 3,3',4,4'-tetrachlorobiphenyl (TCB) and 3,3'4,4',5-pentachlorobiphenyl (PnCB). Importantly, the animals with elevated serum levels of 3,3',4,4'-TCB, 3,3',4,4',5-PnCB and an increased total serum TEQ had a high prevalence of endometriosis, and the severity of disease correlated with the serum concentration of 3,3,',4,4'-TCB. Increased serum concentrations of coplanar PCBs were also present in lead-treated animals. Implications of these findings for human health and the prevalence of endometriosis in humans will be discussed.

Differential effects of adult and perinatal lead exposure on morphine-induced locomotor activity in rats

The effects of adult and perinatal lead treatment on the development of locomotor sensitization produced with repeated morphine administration was investigated. In Experiment 1, adult male rats received a diet containing 250 ppm lead acetate or a control diet for 43 days. Animals then received 10 mg/kg morphine sulfate or water vehicle (ip) and locomotor activity was monitored for 14 consecutive days. While both control and lead-exposed animals demonstrated a locomotor sensitization to morphine, the magnitude of the increased locomotor response was reduced in lead-treated animals. Subsequent analysis of blood-lead in the adult lead-exposed animals indicated residue levels ranging between 20 and 30 μg/dl. In Experiment 2, adult female rats were treated daily with 0, 8, or 16 mg lead via gavage for 30 days before breeding with non-exposed males. Lead exposure in dams continued through gestation and until pups were weaned at postnatal day (PND) 21. At PND 60, male offspring received morphine or vehicle challenges identical to those described in Experiment 1. Animals perinatally exposed to dams receiving 16 mg lead daily demonstrated an enhanced behavioral response to morphine relative to control animals. Analysis of offspring blood indicated lead levels below detectable limits (<1 μg/dl) for all animals. The results suggest exposure to lead at environmentally relevant levels produces long-lasting changes in drug-induced behavior, and the developmental period in which lead exposure occurs is a significant contributor to the manifestation of these effects.

Developmental lead exposure disturbs expression of synaptic neural cell adhesion molecules in herring gull brains

Neurobehavioral testing of herring gull chicks ( Larus argentatus) in both laboratory and field studies indicates that lead exposure during critical periods of development causes neurological deficits that may compromise survival in the wild. Accumulating evidence suggests that lead impairs neurodevelopment, in part, by altering the expression of cell adhesion molecules (CAMs) responsible for the proper formation and maintenance of neural structure and synaptic function. We examined the adhesion molecules NCAM, L1, and N-cadherin in gull brains to determine whether these CAMs are altered by lead exposure and might serve as markers of developmental neurotoxicity. One-day-old chicks were collected from nesting colonies and were laboratory housed. On post-hatching day (PHD) 2, chicks were given 100 mg/kg lead acetate or saline (intraperitoneally). Birds were killed on PHD 34, 44, or 55 (blood-lead levels averaged 27.4, 20.8, and 19.5 μg/dl, respectively). Brains were removed and stored at −70°C until analysis. Expression of CAMs was determined in synaptosomal preparations by Western blotting and the activity of NCAM-associated sialyltransferase (ST) was determined in purified whole brain golgi apparatus. Elevation in synaptosomal polysialylated NCAM expression and a significant increase in golgi ST activity was observed in lead-treated animals at PHD 34. Reductions in synaptosomal N-cadherin were observed at PHD 34 and 44, while L1 expression appeared unaffected by lead at any timepoint. By 55 days post-hatching, no differences in N-cadherin expression, polysialylated NCAM expression or NCAM-associated ST activity were seen in lead-treated animals as compared with age-matched control animals. Lead-induced disruption of CAM expression during early neurodevelopment may contribute to behavioral deficits observed in herring gulls in both the laboratory and the field, and may serve as a marker for heavy metal exposure during postnatal development.

Influence of ethanol on lead distribution and biochemical changes in rats exposed to lead

In the present study, an attempt has been made to investigate the effect of ethanol consumption on the distribution of lead in different regions of brain and body organs of male albino rats. Lead when administered intragastrically, for a period of eight weeks resulted in almost uniform accumulation of this metal in all the regions of brain, which increased by almost two fold when ethanol was given along with lead. Lead was also seen to compartmentalise in almost all the tissues of the body to varying extents, with the highest accumulation in the kidney. A progressive and appreciable accumulation of lead was seen in blood with a concomitant increase in ZPP levels in animals during the course of treatment, which increased further when ethanol was administered along with lead. The activity of δ-ALAD and AChE in blood was significantly decreased in lead as well as ethanol treated animals. However, in animals coexposed to lead and ethanol, the inhibition of δ-ALAD was not significantly different, when compared to only lead-treated animals. The results suggested that animals exposed to ethanol and lead simultaneously accumulate higher levels of lead in blood and brain of animals making them more vulnerable to the haematological and neurological toxic effects of lead.

Ethanol potentiates lead-induced inhibition of rat brain antioxidant defense systems.

We investigated the effect of alcohol (3 g/kg body weight intragastrically) on lead-induced (50 mg/kg body weight intragastrically) oxidative stress in adult rat brain. Ethanol was found to potentiate the accumulation of lead in the rat brain by 100%. Lead and ethanol in combination also enhanced lipid peroxidation, a deteriorative process of biomembranes, and markedly decreased the antioxidant capacity of neuronal cells in terms of reduced activities of antioxidant enzymes i.e., superoxide dismutase, catalase and glutathione peroxidase. Further, the activity of glutathione reductase was also significantly decreased in lead and ethanol co-exposed animals as compared to only lead-treated animals, which had altered glutathione status. The results of the present study show that ethanol makes the adult rat brain more susceptible to the neurotoxic effects of lead by accentuating the oxidative stress induced by lead.

Experimental Lead Toxicosis of Raccoons (Procyon lotor)

Four pairs of raccoons were treated orally with the following doses of lead acetate (mg/kg; 5 days/week, for 8 weeks): 0 (control), 1,2 and 4. In the six experimental animals, this treatment produced dose-dependent increases in blood lead, without clinical signs or changes in haematological parameters. After 8 weeks, the liver and kidney of all lead-treated animals and the calvarium and radius of those receiving doses of 2 and 4 mg/kg contained elevated concentrations of lead. Acid-fast inclusions were observed by light and electron microscopy in the kidneys of all raccoons receiving the two highest doses and in one animal receiving the lowest dose. Hepatic acid-fast inclusions were seen in only one animal (dose 4 mg/kg). No inclusions were seen in osteoclasts of the radius. It is suggested that the findings, which support earlier observations that raccoons are fairly resistant to lead, may be of value in studying interactions between lead exposure and oral vaccination of wildlife against rabies.