Rare cases of severe life-threatening lead poisoning due to accident or chronic occupational exposure to lead and manganese: Diagnosis, treatment, and prognosis.

BACKGROUND: Chronic long-term, low-dose environmental and occupational exposure to lead (Pb) has been extensively studied in large cohorts worldwide among general populations, miners, smelters, or battery workers. However, studies on severe life-threatening Pb poisoning due to accidental or chronic occupational exposure to Pb and manganese (Mn) were rarely reported. METHODS: We present one case of acute severe Pb poisoning and compare it with another severe chronic occupational exposure case involving Pb and Mn. A 27-year-old woman mistakenly took a large quantity of pure Pb powder as an herbal remedy; she developed abdominal colic, severe nausea, vomiting, fatigue, and cutaneous and sclera icterus. Laboratory tests showed her blood lead level (BLL) of 173.5 µg dL-1 and urinary lead level (ULL) of 1240 µg dL-1. The patient was diagnosed with acute Pb poisoning and acute liver failure. In another chronic exposure case, a 56-year-old man worked in a Pb and Mn smelting factory for 15 years. He was brought to the emergency room with severe nausea, vomiting, and paroxysmal abdominal colic, which was intolerable during the onset of pain. His BLL was 64.8 µg dL-1 and ULL was 38 µg dL-1, but his blood and urinary Mn levels were normal. The patient was diagnosed with chronic Pb poisoning. Both patients received chelation therapy with calcium disodium ethylene-diamine-tetraacetate (CaNa2EDTA). The woman with acute severe Pb intoxication recovered well and was discharged from the hospital after treatment, and the man who survived severe Pb poisoning was diagnosed with lung cancer. CONCLUSION: Clinical manifestations of acute and chronic severe Pb poisoning are different. Chelation therapy with CaNa2EDTA is proven to be an effective life-saving therapy in both cases by reducing BLL. Occupational exposure to both Pb and Mn does not appear to increase Mn neurotoxicity; however, the probability that co-exposure to Mn may increase Pb toxicity in the same patient cannot be excluded.

Chronic occupational exposure to lead leads to significant mucocutaneous changes in lead factory workers.

BACKGROUND: Chronic lead toxicity is a worldwide public health problem. Lead possesses deleterious effects on many organ systems. However, little is known regarding its clinical and biophysical effects on the skin. OBJECTIVE: To investigate mucocutaneous signs and biophysical property changes in skin after chronic lead toxicity. METHODS: One hundred and eighty-seven patients who were car battery workers participated in the study. Complete history and physical examination were performed. Blood was collected for laboratory analyses. Thorough skin examination by dermatologists was carried out in 134 subjects. Additionally, 96 patients with blood lead levels (BLL) >70 µg/dL were further evaluated for skin elasticity, sebum content, transepidermal water loss (TEWL), hydration, pH and pigmentation. An equal number of age-, sex- and skin-type-matched subjects were recruited as controls. RESULTS: The mean BLL of all subjects was 74.15 ± 11.58 µg/dL. The most frequently observed signs were gingival brown pigmentation in 112 (83.6%), gingivitis in 111 (82.8%) and lead line in 66 (49.3%) patients. The lead line was found in subjects with significantly higher BLLs (adjusted mean difference 6.45, 95% CI 2.30-10.60 µg/dL, P = 0.003) and in association with gingivitis (adjusted OR 7.32, 95% CI 2.08-25.74, P = 0.002). Mean BLL of the patients who underwent biophysical assessment was 82.77 ± 9.80 µg/dL. Patients exhibited a statistically significant lower skin hydration observed by corneometer as well as elasticity. The adjusted ORs of having dry skin and lower elasticity were 15.32 (95% CI 4.41-53.24), P < 0.001) and 1.96 (95% CI 1.06-3.60), P = 0.031), respectively. These differences were not significant for sebum content, TEWL, pH and pigmentation. CONCLUSION: Importantly, even in normal-appearing skin, level of hydration and elasticity decreased in lead-intoxicated patients. These results suggest that lead might possess harmful effects on the skin at measurable levels.

The effects of occupational lead exposure on selected inflammatory biomarkers.

In exposure to toxic metals such as lead, determining lead and cytokine levels (IL-6, IL-10, and TNF-α) is essential for early detection of diseases. The aim of this study was to develop an model for early detection of inflammation and onset of atherosclerosis in the absence of clinical findings in young workers, which could help physicians take timely an action and start treatment. This study included 49 metal workers exposed to lead occupationally and 50 unexposed administrative workers (controls) who underwent immunological analysis for cytokines (IL-6, IL-10, and TNF-α) and atherosclerosis markers (h-FABP and VCAM-1), toxicological analysis for lead, and routine biochemical analysis (ALT, AST, creatinine) at the Ankara Occupational and Environmental Diseases Hospital in 2017. Lead levels correlated with IL-6, IL-10, and TNF-α (r=0.469, r=0.521 and r=0.279, respectively, p<0.01) but did not significantly affect h-FABP and VCAM-1 levels.

ECG conduction disturbances and ryanodine receptor expression levels in occupational lead exposure workers.

OBJECTIVES: A significant number of researches have evidenced that occupational lead (Pb) exposure increased risks of cardiovascular disease. However, evidences about the potential effects of Pb on the cardiac conduction system are sparse and inconclusive. Besides, ryanodine receptors (RyRs) induced dysfunction of cardiac excitation contraction coupling which is considered to be one of the mechanisms in cardiovascular diseases. Therefore, we examined the association between occupational Pb exposure and ECG conduction abnormalities, as well as RyRs in Pb-induced ECG abnormalities. METHODS: We investigated 529 Pb smelter workers, and measured blood lead (BPb), zinc protoporphyrin (ZPP), ECG outcomes and RyR expression levels. Based on BPb levels, the workers were divided into three groups: the BPb not elevated group, the BPb elevated group and the Pb poisoning group. Descriptive and multivariable analyses were performed. RESULTS: Compared with the BPb not elevated group, the Pb poisoning group had a higher incidence of high QRS voltage, and a lower level of RyR1 gene expression (p<0.05). Further unconditional multivariable logistic regression analyses showed that high QRS voltage was positively related to BPb (OR=1.045, 95% CI 1.014 to 1.078) and inversely associated with RyR1 expression (OR=0.042, 95% CI 0.002 to 0.980) after adjusting for potential confounders. In addition, multiple linear regression analyses showed that the QTc interval was positively associated with ZPP (ß=0.299, 95% CI 0.130 to 0.468) after adjusting for potential confounders. CONCLUSIONS: Our study provided evidences that occupational exposure to Pb may be associated with worse ECG outcomes (high QRS voltage), which might be related to decreased levels of RyR1.

Impact of chronic lead exposure on liver and kidney function and haematologic parameters.

BACKGROUND: Lead, one of the most widely used metals because of its beneficial physical properties, has been reported to adversely influence several different organs and organ systems. The aim of the present study was to examine the effect of lead exposure on liver and renal function and haematologic parameters. METHODS: This was a case-cohort study comparing adults with occupational, environmental or opium-related lead exposure with blood lead levels [BLL] >10 µg/dL (High blood lead level (HBLL) group and age- and gender-matched normal healthy individuals (Low blood lead level [LBLL] group with BLL <10 µg/dL). The complete blood count and concentrations of serum creatinine, urea, aspartate aminotransferase (AST), alanine aminotransferase (ALT) were recorded for subsequent investigation. RESULTS: The mean BLL was significantly higher in the HBLL than in the LBLL groups (51.36 ± 44.72 vs 4.17 ± 1.97 µg/dL). The Spearman's rho revealed a significant association between BLL and urea (r = 0.25, P < 0.001), creatinine (r = 0.16, P = 0.02), AST (r = 0.42, P < 0.001) and ALT (r = 0.27, P < 0.001). The median [IQR] serum urea (34 mg/dL [27-221]) vs (30 [27-36]), creatinine (0.9 mg/dL [0.8-1]) vs (0.8 [0.7-0.9]), ALT (25 mg/dL [16-49]) vs (22 [16-30]) and AST concentrations (29 mg/dL [20-42]) vs (20 [18-24]) were all significantly higher (P < 0.05) in the HBLL group compared to the LBLL group. The median [IQR] haemoglobin (12.6 g/dL [10.4-15.4]) vs (15.2 [14.6-16.3] and haematocrit (36.9% [31-44.8]) vs (45.6 [43.6-48.2]) were both significantly lower (P < 0.001) in the HBLL group than in the LBLL group. CONCLUSION: The results indicated that people with chronic lead exposure with BLLs greater than 10 µg/dL are at risk of renal, liver and haematologic impairments.

Oxidative stress in opium users after using lead-adulterated opium: The role of genetic polymorphism.

Use of lead-adulterated opium has become one of the major sources of lead poisoning in Iran. This study was designed to assess clinical effects and oxidative stress and its association with GSTM1, GSTT1, NQO1, and ALAD genes polymorphisms and blood lead level (BLL) in lead-adulterated opium users. The oxidative stress status in 192 opium users with lead poisoning symptoms measured and compared with 102 healthy individuals. Gluthatione S-transferase (GST)-M1 and -T1 genes deletion, NQO1 rs1800566, and δ-aminolevulinic acid dehydratase (ALAD) rs1800435 polymorphisms were determined using PCR and PCR-RFLP. The relation between the polymorphisms, BLL, and oxidative stress parameters were analysed using multivariate linear regressions. The common symptoms of lead toxicity were gastrointestinal and neurologic complications. Oxidative stress was significantly higher in opium addicts and lipid peroxidation significantly correlated with BLL. There was significant association between ALAD rs1800435 and BLL, and the BLL was significantly lower in the patients with ALAD 1-2 genotype. Use of lead-adulterated opium causes high frequency of lead toxicity symptoms, hematological and biochemical abnormalities, and oxidative stress which are associated with BLL. Route of opioid use and the polymorphism of rs1800435 in ALAD gene are the major determinants of BLL in lead-adulterated opium users.

[Study on the health effects of occupational exposure to lead exceeded].

Objective: The main purpose of this study was to explore the health effects of occupational exposure to lead exceeded. Methods: We collected 114 inpatients who exposure to lead, and diagnosed lead toxicity by No. 5 Suzhou People's Hospital from January 2011 to May 2018. Samples were selected according to 1:4 of the lead exceeded group and the control group. The age and gender of the lead exce eded group were matchied, and balanced between the two groups. Lead exceeded group: 84 inpatients occupational exposure to lead, whose blood or urinary lead exceeded. Control group: 336 healthy checkup persons who did not contact with any toxic or hazardous substances. Results: The diastolic blood pressure of lead exceeded group was significantly higher than control group (P<0.05) . The red blood cell count, hemoglobin, mean red blood cell volume, mean hemoglobin content, mean hemoglobin concentration, the platelet count, and the lymphocyte count levels of lead exceeded group were significantly lower than control group (P<0.05) , while the average platelet volume level of lead exceeded group was significantly higher than control group (P<0.05) . The aspartate aminotransferase, glucose and the urea nitrogen levels of lead exceeded group were significantly higher than control group, while the creatinine of lead exceeded group was significantly lower than control group (P<0.05) . The total protein, albumin, cholesterol and low density lipoprotein levels of lead exceeded group were significantly lower than control group (P<0.05) . The abnormal rate of electrocardiogram and spleen B (24.4%, 8.33%) in lead exceeded group were significantly higher than control group (11.04%, 0.6%) (P<0.05) . The abnormal rate of liver B ultrasound, and gallbladder B ultrasound (23.81%、8.32%) in lead exceeded group were significantly lower than control group (41.32%、21.06%) (P<0.05) . Conclusion: Occupational exposure to lead exceeded not only has a significant impact on red blood cell related indicators, but also has a certain impact on cardiac function and liver and kidney functions. It is suggested that lead exprsure may have some effect on health of occupational population.

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

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

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

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

Early Life Pb Exposure and its Effect on Later Life Retinal Degeneration.

The study presents the longitudinal effect of early life lead exposure on retinal ischemia. Swiss albino mice were exposed to lead acetate at two different timepoints viz. postnatal day 1-20 and at 7th week of age. These mice were then followed till 10 week of age and subjected to retinal ischemia. Retinal ischemia was induced using pterygopalatine artery ligation. The effect of prior lead exposure on ischemic insult was determined using various histological and molecular parameters. Although toxic effects of Pb are well reported, but the results in this study showed not much significant effect of early life Pb exposure on later life retinal degeneration. While retinal thickness was decreased in surgery group and 7th week Pb exposed group, PND Pb exposed mice showed retinal thickness comparable to normal control. There was no difference in TUNEL positive cells in Pb exposed group when compared to surgery group. The molecular studies revealed overexpression of BDNF and GFAP in PND Pb exposed mice reflecting more injury and inflammation. The combined results revealed that Pb exposure have mild effect on overall susceptibility to retinal damage in later life. The Pb may exert its toxic effects at longer duration and thus the toxic effects may be mapped at longer timepoints. The study provides a new dimension to the already well known toxic effects of lead which needs to be further explored. J. Cell. Biochem. 118: 3213-3224, 2017. © 2017 Wiley Periodicals, Inc.

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

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

Multiple pathological fractures and delayed union associated with lead exposure in a German Shepherd Dog.

CASE REPORT: An 8-year-old 40.8-kg intact male German Shepherd Dog was evaluated for bilateral antebrachial fractures. Radiographs revealed osteopenia and comminuted proximal diaphyseal fractures of the left radius and ulna, and proximal articular fracture of the right ulna. A dual energy X-ray absorptiometry scan confirmed decreased bone mineral density. Bone mineral analysis collected at the time of definitive surgical repair demonstrated high lead concentration. Analysis further demonstrated normal bone calcium and phosphorus concentrations. Serum lead concentration was normal. The left radial and ulnar fractures were surgically stabilised with an external fixator. The right ulnar fracture was splinted. The left antebrachial fractures were palpably unstable at 12 weeks after surgery. Moderate callus formation and incomplete bone union were present at 17 weeks postoperatively. The dog was re-presented 15 months later for right metacarpal and left metatarsal fractures, which were managed conservatively. Complete bone union of the right radial and ulnar fractures was not present at that time. CONCLUSION: Excessive lead accumulation in bone should be considered as a differential diagnosis for increased susceptibility to pathologic fracture and delayed fracture healing in dogs.

Lead Exposure in Different Organs of Mammals and Prevention by Curcumin-Nanocurcumin: a Review.

Chronic lead exposure is related to many health diseases in mammals. Exposure to lead forms reactive oxygen species reducing body antioxidant enzymes inflicting injury to numerous macromolecules or cell necrosis. Recent studies have revealed oxidative stress as the vital mechanism for lead toxicity. Lead is found to be toxic to several organ systems such as hematopoietic, skeletal, renal, cardiac, hepatic, and reproductive systems and extremely toxic to the central nervous system (CNS). Curcumin, an active ingredient of the dietary spice, and nanocurcumin, a nanoform of curcumin, are found to decrease toxicity due to lead in various organ systems in mouse models. Higher bioavailability, chelating property, and retention time of nanocurcumin over bulk curcumin may pave the way to expand the utility of nanocurcumin to remove lead toxicity from various organ systems within humans.

Role of delta-aminolevulinic acid in the symptoms of acute porphyria.

BACKGROUND: Attacks of neuropathic pain, usually abdominal, are characteristic of the acute porphyrias and accompanied by overproduction of heme-precursor molecules, specifically delta-aminolevulinic acid and porphobilinogen. The basis for the acute symptoms in these diseases has been speculative. METHODS: We review genetic acute porphyria, hereditary tyrosinemia, and an acquired condition, lead poisoning. All perturb heme synthesis and present with a similar pain syndrome. RESULTS: Although each of these conditions has characteristic urine biochemistry, all exhibit excess delta-aminolevulinic acid. Moreover, in all, treatment with hemin reduces delta-aminolevulinic acid and relieves symptoms. In contrast, use of recombinant porphobilinogen deaminase to knock down porphobilinogen in acute porphyria was ineffective. CONCLUSIONS: There is now convincing evidence that delta-aminolevulinic acid is the cause of pain in the acute porphyrias. The efficacy of hemin infusion is due mainly, if not entirely, to its inhibition of hepatic delta-aminolevulinic acid synthase-1, the enzyme that catalyzes delta-aminolevulinic acid formation. Delta-aminolevulinic acid synthase-1 is a rational target for additional therapies to control symptoms in acute porphyria.

Co-exposure to lead increases the renal response to low levels of cadmium in metallurgy workers.

PURPOSE: Research on the effect of co-exposure to Cd and Pb on the kidney is scarce. The objective of the present study was to assess the effect of co-exposure to these metals on biomarkers of early renal effect. METHODS: Cd in blood (Cd-B), Cd in urine (Cd-U), Pb in blood (Pb-B) and urinary renal biomarkers, i.e., microalbumin (µ-Alb), beta-2-microglobulin (ß2-MG), retinol binding protein (RBP), N-acetyl-ß-d-glucosaminidase (NAG), intestinal alkaline phosphatase (IAP) were measured in 122 metallurgic refinery workers examined in a cross-sectional survey. RESULTS AND CONCLUSIONS: The median Cd-B, Cd-U, Pb-B were: 0.8 µg/l (IQR = 0.5, 1.2), 0.5 µg/g creatinine (IQR = 0.3, 0.8) and 158.5 µg/l (IQR = 111.0, 219.3), respectively. The impact of Cd-B on the urinary excretion of NAG and IAP was only evident among workers with Pb-B concentrations ≥ 75th percentile. The association between Cd-U and the renal markers NAG and RBP was also evidenced when Pb-B ≥ 75th percentile. No statistically significant interaction terms were observed for the associations between Cd-B or Cd-U and the other renal markers under study (i.e., µ-Alb and ß2-MG). Our findings indicate that Pb increases the impact of Cd exposure on early renal biomarkers.

Blood lead level modifies the association between dietary antioxidants and oxidative stress in an urban adult population.

Oxidative stress may be affected by lead exposure as well as antioxidants, yet little is known about the interaction between dietary antioxidants and blood lead levels (BLL) on oxidative stress level. We investigated the interaction between dietary antioxidants and BLL on oxidative stress level. As part of the Biomarker Monitoring for Environmental Health conducted in Seoul and Incheon, Korea, between April and December 2005, we analysed data from 683 adults (female = 47·4 %, mean age 51·4 (sd 8·4) years) who had complete measures on BLL, dietary intakes and oxidative stress marker (urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG)). Dietary intakes were assessed by a validated semi-quantitative FFQ, BLL was measured using atomic absorption spectrophotometry, and 8-OHdG by ELISA. Multivariate linear regression analyses were used to evaluate the influence of BLL on the association between dietary antioxidants and 8-OHdG. Geometric means of BLL and 8-OHdG concentrations were 4·1 (sd 1·5) µg/dl and 5·4 (sd 1·9) µg/g creatinine, respectively. Increases of vitamins C and E were significantly associated with the decrease of log10 8-OHdG in the adults from the lowest quartile of the BLL group (≤ 3·18 µg/dl, geometric mean = 2·36 µg/dl) than those of the highest quartile BLL group (>5·36 µg/dl, geometric mean = 6·78 µg/dl). Regarding antioxidant-related foods, vegetables excluding kimchi showed a higher inverse relationship with 8-OHdG in the lowest quartile BLL group than the highest group. These findings suggest a rationale for lowering the BLL and increasing the intake of dietary antioxidants in the urban population in Korea.

Renal health and the environment: heavy metal nephrotoxicity.

We currently recognise that environmental toxins such as cadmium, lead, and arsenic play a significant role in the development of chronic renal failure. Epidemiological studies have shown a strong association between exposure to these metals and the presence of chronic kidney injury. The physiopathological mechanisms behind metal-induced kidney injury are complex, and some aspects of their metabolism and damage mechanisms remain unknown. This review aims to analyse the physiopathological mechanisms of kidney injury due to cadmium, lead and arsenic.

Low-level lead exposure increases systolic arterial pressure and endothelium-derived vasodilator factors in rat aortas.

Chronic lead exposure induces hypertension and alters endothelial function. However, treatment with low lead concentrations was not yet explored. We analyzed the effects of 7 day exposure to low lead concentrations on endothelium-dependent responses. Wistar rats were treated with lead (1st dose 4 µg/100 g, subsequent dose 0.05 µg/100 g, i.m. to cover daily loss) or vehicle; blood levels attained at the end of treatment were 9.98 µg/dL. Lead treatment had the following effects: increase in systolic blood pressure (SBP); reduction of contractile response to phenylephrine (1 nM-100 µM) of aortic rings; unaffected relaxation induced by acetylcholine (0.1 nM-300 µM) or sodium nitroprusside (0.01 nM-0.3 µM). Endothelium removal, N(G)-nitro-L-arginine methyl ester (100 µM) and tetraethylammonium (2 mM) increased the response to phenylephrine in treated rats more than in untreated rats. Aminoguanidine (50 µM) increased but losartan (10 µM) and enalapril (10 µM) reduced the response to phenylephrine in treated rats. Lead treatment also increased aortic Na(+)/K(+)-ATPase functional activity, plasma angiotensin-converting enzyme (ACE) activity, protein expression of the Na(+)/K(+)-ATPase alpha-1 subunit, phosphorylated endothelial nitric oxide synthase (p-eNOS), and inducible nitric oxide synthase (iNOS). Our results suggest that on initial stages of lead exposure, increased SBP is caused by the increase in plasma ACE activity. This effect is accompanied by increased p-eNOS, iNOS protein expression and Na(+)/K(+)-ATPase functional activity. These factors might be a compensatory mechanism to the increase in SBP.

Protective effects of omega-3 fish oil on lead-induced impairment of long-term potentiation in rat dentate gyrus in vivo.

In order to evaluate the effect of omega-3 fish oil supplement by gavage (0.4 mL/100 g body weight) on the chronic lead-induced (0.2% lead acetate) impairments of long-term potentiation (LTP) in rat dentate gyrus (DG) in vivo, we designed the experiments which were carried out in four groups of newborn Wistar rats (the control, the lead-exposed, the control with fish oil treatment and the lead-exposed with fish oil treatment, respectively). The excitatory postsynaptic potential (EPSP) and population spike (PS) amplitude were measured in the DG of rats with above different treatments at the age of 80-90 d in response to stimulation applied to the lateral perforant path. The results showed (1) postnatal chronic lead-exposure impaired LTP measured on both EPSP slope and PS amplitude in DG area of the hippocampus; (2) in the control rats, omega-3 fish oil had no effect on LTP while in the lead-exposed rats, omega-3 fish oil had a protective effect on LTP. These results suggest that omega-3 fish oil supplement could protect rats from the lead-induced impairment of LTP. Omega-3 fish oil might be a preventive substance in reducing LTP deficits induced by lead.

Iron, Lead, and Children's Behavior and Cognition.

Iron deficiency (ID) is the most common micronutrient deficiency in the world, with consequences of ID and ID anemia (IDA) in young children including behavioral and cognitive deficits. In turn, lead exposure is one of the most common environmental toxicants affecting children. Elevated blood lead levels (BLLs) in young children are also associated with behavioral and cognitive deficits. The metabolic and physiological connections between iron and lead, including a common route of entry into the body and similar neural targets, suggest a considerable overlap in their effects on functional outcomes. Very few studies have examined the existence of increased susceptibility to lead neurotoxicity in children with ID, but there is evidence that ID and BLL are independently associated with cognition and behavior. Children's susceptibility to both ID and elevated BLLs will likely depend on the timing and severity of both exposures, something that should be investigated systematically.