Urinary Pb Research Articles

Effects of exposure to polycyclic aromatic hydrocarbons and heavy metals on the oxidative stress, inflammation and DNA methylation among traffic conductors

Background: Exposure to traffic-related air pollutants, including polycyclic aromatic hydrocarbons (PAHs) and heavy metals, has been associated with the etiology and prognosis of many diseases including cardiovascular events. However, the specific causal agents and underlying mechanisms for different adverse health effects remain unclear. Objectives: The aims of this study were to examine the relations of exposure to PAHs (1-hydroxypyrene-glucuronide, 1-OHPG) and metals (cadmium, Cd; nickel, Ni; lead, Pb; and copper, Cu) with lipid peroxidation (4-hydroxynonenal, 4-HNE), inflammation (high-sensitive C-creative protein, hs-CRP), endothelial function (vascular cell adhesion molecule-1,VCAM-1; intercellular adhesion molecule-1, ICAM-1), DNA damage (8-hydroxydeoxyguanosine, 8-OHdG) and DNA methylation (long interspersed nuclear element-1, LINE-1). Methods: we recruited 91 traffic conductors and 53 indoor official workers between May 2009 and June 2011 in Taipei, Taiwan. Post-shift blood and urine samples from 2 consecutive days were collected. The urine samples were analyzed for 1-OHPG, Cd, Ni, As, Pb, Cu, and 8-OHdG. The blood samples were measured for HNE, hs-CRP, VCAM-1, ICAM-1, and LINE-1. We constructed a linear mixed model to assess these associations adjusted for covariates. Results: We found that urinary 1-OHPG levels were positively associated with urinary 8-OHdG levels (β=0.09, p=0.026), and urinary 8-OHdG levels were negatively associated with LINE-1 methylation levels (β= -0.85, p=0.021) among traffic conductors. Significant positive relations between urinary As and Pb levels and HNE levels, and between all urinary metals levels and ICAM-1 levels, and between urinary Pb levels and VCAM-1 levels, as well as between urinary Ni levels and hs-CRP levels were observed in traffic conductors. Conclusions: Exposure to PAHs and metals could increase the burden of oxidative stress and inflammation, and oxidative stress could result in global DNA hypomethylation.

Heavy metal exposure, in combination with physical activity and aging, is related with oxidative stress in Japanese women from a rural agricultural community.

This study aimed to evaluate the relationships between oxidative stress and heavy metal exposure (lead [Pb] and cadmium [Cd]), as well as co-factors such as physical activity and age, in Japanese women. This study was conducted with female subjects from a rural agricultural community in Japan. Subjects were asked to complete lifestyle-related questionnaires and undergo a group health examination. Physical activity, alcohol consumption, body mass index, and other demographic information were collected. Blood and urine samples were collected to measure urinary 8-hydroxydeoxyguanosine (8-OHdG) levels and blood and urinary Cd and Pb concentrations. Urine samples were analyzed using high performance liquid chromatography and flameless atomic absorption spectrometry; blood samples were analyzed using inductively coupled plasma-mass spectrometry. Age, physical activity, and blood and urinary Cd and Pb concentrations were included in structural equation modeling analysis. Two latent factors for heavy metal exposure and physical activity were produced to predict the total influence of the variables. The final model was good: CMIN/DF = 0.775, CFI = 1.000, GFI = 0.975, AGFI = 0.954, RMSEA = 0.000. 8-OHdG levels were positively associated with heavy metal exposure, physical activity, and age (standard β of path analysis: 0.33, 0.38, and 0.20, respectively). Therefore, oxidative stress is associated with both, environmental and lifestyle factors, in combination with aging.

Urinary and blood cadmium and lead and kidney function: NHANES 2007-2012.

Cadmium (Cd) and lead (Pb) are widespread environmental contaminants that are known nephrotoxins. However, their nephrotoxic effects at low-environmental exposure levels are debated. We examined the association of blood Pb (B-Pb), blood Cd (B-Cd), urinary Pb (U-Pb) and urinary Cd (U-Cd) with estimated glomerular filtration rate (eGFR) and urinary albumin (ALB). We used multivariate linear regression to analyze the association between B-Pb, B-Cd, U-Pb, and U-Cd with eGFR and ALB in adult participants (≥20 years of age) in NHANES 2007-2012. The dataset was limited to NHANES individuals with both blood and urinary metal measurements. We found a statistically significant inverse association between eGFR and B-Cd and statistically significant positive associations between eGFR and both U-Cd and U-Pb, as well as statistically significant associations between ALB and the 3rd and 4th quartiles of U-Cd. The inverse association between eGFR and B-Cd, in conjunction with positive associations between eGFR and ALB with U-Cd, suggest that U-Cd measurement at low levels of exposure may result from changes in renal excretion of Cd due to kidney function and protein excretion. However, renal effects such as hyperfiltration from Cd-mediated kidney damage or creatinine-specific Cd effects cannot be excluded with this cross-sectional design.

Urinary heavy metals in Hispanics 40–85 years old in Doña Ana County, New Mexico

ABSTRACTExposure to As, Cd, Pb, and U among older Hispanic adults residing in underserved communities in southern New Mexico was investigated. Personal information was obtained by standardized interview from 188 adults aged 40–85 years. Urinary metal concentrations were measured and compared to results from the National Health and Nutritional Examination Survey (NHANES). Urinary As and U in study participants significantly (p < .05) exceeded NHANES reference values. Elevated urinary As concentration was significantly associated with older age, Latin American birthplace, clinic site, private-well drinking water, higher self-rated health, and diabetes. Higher urinary Cd was significantly associated with older age, clinic site, female sex, agricultural work, and current cigarette smoking. No personal characteristics were significantly associated with urinary Pb or U. Our results suggest elevated levels of As and U in this population.

Simultaneous Exposure to Heavy Metals among Residents in the Industrial Complex: Korean National Cohort Study.

A survey was conducted to evaluate the multi-exposure level and correlation among toxic metal biomarkers (Cd, Pb, and Hg). A total of 592 individuals who participated in the survey were residents near an industrial complex in Gwangyang and Yeosu (exposed group) and of Hadong and Namhae (control group) in southern Korea from May 2007 to November 2010. The Gwangyang and Yeosu area exposed groups had slightly higher blood Pb (2.21 and 1.90 µg/dL), urinary Cd observed values (2.20 and 1.46 µg/L), urinary Cd with a urinary creatinine correction (1.43 and 1.25 µg/g Cr), and urinary Hg observed values (2.26 and 0.98 µg/L) in women participants than those in the Hadong and Namhae area (control group). Blood Pb (3.18 and 2.55 µg/dL), urinary Hg observed values (1.14 and 0.92 µg/L), and urinary Hg with a urinary creatinine correction (1.06 and 0.96 µg/L) for male participants were also slightly higher than those in the Hadong and Namhae area (control group). The correlation among urinary Cd, Hg and Pb concentrations in the blood was significant. We suggest that the exposed group of residents were simultaneously exposed to Pb, Cd, and Hg from contaminated ambient air originating from the iron manufacturing industrial complex.

Food intake survey of kindergarten children in Korea: Part 3 cadmium and lead burden.

This study was initiated to elucidate the extent of dietary exposure of children in Korea to two pollutant metals of cadmium (Cd) and lead (Pb). Possible urban-rural difference was also examined. Food duplicate and morning spot urine samples were collected from 108 children in 4 kindergartens (KG) (1 KG in Seoul and 3 KGs in Jeju Island), as reported in a previous publication. The samples were analyzed for Cd and Pb by ICP-MS. Cd and Pb in food duplicate and urine samples were distributed approximately log-normally. Geometric means for Cd and Pb in food duplicate samples were 12.4 and 5.8 μg/day, or 0.58 and 0.27 μg/kg body weight/day, respectively, and the values for Cd and Pb in urine (as observed, i.e., with no correction for urine density) were 0.91 and 1.64 μg/L, respectively. 2.41 and 0.30 μg/day of Cd and Pb (accounting for 19.5 and 5.1%) came from boiled rice, the staple food. The levels of Cd and Pb burden among the children in the present survey were essentially the same with the levels reported for children in Pusan. The reasons for difference in the rank in Cd-D and Cd-U among the 4 KGs need further study. The observed levels of Cd and Pb exposure were more or less similar to what were reported for children in Pusan. No apparent urban-rural difference could be detected.

Arsenic and Manganese Alter Lead Deposition in the Rat

Lead (Pb) continues to be a major toxic metal in the environment. Pb exposure frequently occurs in the presence of other metals, such as arsenic (As) and manganese (Mn). Continued exposure to low levels of these metals may lead to long-term toxic effects due to their accumulation in several organs. Despite the recognition that metals in a mixture may alter each other's toxicity by affecting deposition, there is dearth of information on their interactions in vivo. In this work, we investigated the effect of As and Mn on Pb tissue deposition, focusing on the kidney, brain, and liver. Wistar rats were treated with eight doses of each single metal, Pb (5mg/Kgbw), As (60mg/L), and Mn 10mg/Kgbw), or the same doses in a triple metal mixture. The kidney, brain, liver, blood, and urine Pb, As, and Mn concentrations were determined by graphite furnace atomic absorption spectrophotometry. The Pb kidney, brain, and liver concentrations in the metal-mixture-treated group were significantly increased compared to the Pb-alone-treated group, being more pronounced in the kidney (5.4-fold), brain (2.5-fold), and liver (1.6-fold). Urinary excretion of Pb in the metal-mixture-treated rats significantly increased compared with the Pb-treated group, although blood Pb concentrations were analogous to the Pb-treated group. Co-treatment with As, Mn, and Pb alters Pb deposition compared to Pb alone treatment, increasing Pb accumulation predominantly in the kidney and brain. Blood Pb levels, unlike urine, do not reflect the increased Pb deposition in the kidney and brain. Taken together, the results suggest that the nephro- and neurotoxicity of "real-life" Pb exposure scenarios should be considered within the context of metal mixture exposures.

Relationship between passive smoking exposure and urinary heavy metals and lung functions in preschool children

Environmental tobacco smoke (ETS) exposure is a risk factor for asthma in school-age children, but there is limited data of ETS exposure on respiratory health in preschool children. This study investigated the relationship between ETS, lead (Pb), and cadmium (Cd) exposures and asthma symptoms and spirometric indices in Chinese preschoolers. Preschool children from 30 nurseries and kindergartens performed spirometry with incentives of animation programs, and their urinary cotinine, Pb and Cd concentrations were measured by immunoassay and inductively coupled plasma-mass spectrometry, respectively. Two thousand seven hundred sixty-three preschoolers participated, and 1,505 and 893 provided valid spirometric data and urine samples, respectively. Current domestic smoking was reported in 37.5% of children, but only 95 (10.6%) had high urinary cotinine-to-creatinine ratio (≥30 ng/mg). Pb was measurable in 3.9% of samples, whereas 406 (45.5%) children had high Cd. Reported ETS exposure was not associated with any spirometric index, whereas cotinine-to-creatinine ratio was inversely associated with forced expiratory volume in 0.5-sec (β = -0.093, P = 0.003), forced expiratory flow between 25% and 75% of expiration (β = -0.138, P = 0.002) and peak expiratory flow (β = -0.106, P = 0.002). Cd exposure was not associated with reported respiratory symptom or spirometric indices. This community study shows that ETS exposure defined by urinary cotinine is a strong risk factor for lung function impairment measured by spirometry in Chinese preschool children. Urinary cotinine is more reliable than questionnaire for assessing ETS exposure in young children. Although high urinary Cd is common in Hong Kong preschoolers, such biomarker is not associated with any clinical or spirometric outcome.

Cadmium and lead in Hong Kong school children

Cadmium (Cd) and lead (Pb) are toxic elements in our environment. This study is to determine the reference intervals of Cd and Pb in blood and urine from Hong Kong school children and to identify their determinants. A total of 2209 secondary school children and 893 preschool children were recruited. Cd and Pb in blood and urine were measured by inductively-coupled plasma mass spectrometry. Blood Cd was affected by age, smoking and residential district, while urine Cd was influenced by age and blood Cd. Blood Cd was positively correlated with smoking as confirmed by urinary cotinine (rho = 0.183, p < 0.001, n = 2074). Blood Pb was dependent on gender and residential district, while urinary Pb was dependent on gender and blood Pb. Students from schools of lower academic grading had higher blood Cd and Pb than those from higher academic grading schools (p < 0.001, respectively). Urinary albumin was positively associated with urinary Cd and Pb. Using a non-occupationally exposed population, the reference ranges are: blood Cd < 21.9 nmol/L for smokers and < 8.8 nmol/L for non-smokers, and blood Pb < 203.8 nmol/L. Reference intervals for urinary Cd and Pb are also reported.

Protective effects of puerarin on experimental chronic lead nephrotoxicity in immature female rats

Puerarin (PU), a natural flavonoid, has been reported to possess anti-oxidative and anti-inflammatory activities. In the present study, female Sprague-Dawley rats received lead (Pb) nitrate (300mg/L, via drinking water) and/or PU (400mg/kg/day, orally) to investigate the protective effects of PU on Pb-induced renal damage. Renal toxicity was evaluated by detecting urinary proteins excretion as well as levels of serum urea nitrogen and serum creatinine. Ultrastructural observations and real-time quantitative polymerase chain reaction analyses were performed on kidney cortex tissues to identify the mitochondrial damage and quantify gene expression levels of cytochrome oxidase submits (COX-I/II/III), respectively. Renal cell damage was assessed by light microscopic examination. Lipid peroxidation (LPO) levels and antioxidant status in kidney were also evaluated. Animals that received both Pb and PU showed a better renal function than those that received Pb alone, with minor pathological damage. Moreover, PU significantly reduced LPO and markedly restored the enzymatic and non-enzymatic antioxidants levels in kidney of Pb-treated rats, which may be related to its restoring mitochondrial function. Furthermore, PU administration significantly increased urinary Pb excretion and decreased its level in the serum and kidney. In conclusion, these results suggested that PU reduces renal damage induced by chronic Pb administration through its antioxidant properties and chelating ability.

EDTA chelation reappraisal following new clinical trials and regular use in millions of patients: review of preliminary findings and risk/benefit assessment

EDTA chelation therapy is regularly used in thousands of patients worldwide. An FDA approval of more than 50 years ago for heavy metal detoxification prompted many physicians to use EDTA as an alternative medicine for many categories of patients. Recently, NIH initiated the so-called Trial to Assess Chelation Therapy (TACT), which has been designed to evaluate whether EDTA and high dose oral vitamins and mineral therapy could offer clinical, quality of life, and economic benefits for patients with a previous myocardial infraction. A 50% reduction of urinary Pb and improvement of systolic blood pressure was observed in 33 cardiovascular patients following 20 iv administrations. In another study involving 15 patients of different categories, EDTA also has been shown to be an effective and nontoxic chelator for the removal of xenobiotic metals such as Pb, Cd, Ni and Al. Administration of iv EDTA on weekly basis appears to be a sufficient and nontoxic protocol for treating patients with suspected overload and toxicity of xenobiotic metals especially Pb and Cd. The causative effect of xenobiotic metals in cancer, cardiovascular, neurodegenerative, renal and other diseases needs further investigation. Similarly, the use of EDTA chelation therapy in other conditions, which are not related to xenobiotic metal toxicity needs further investigation and confirmation of therapeutic use from controlled randomized clinical trials. Metal balance and drug interaction studies are required to clarify the risk/benefit assessment for the long term use of EDTA in patients with excess xenobiotic metal toxicity and in other conditions.

Estimation of Lead Elimination Rates for Liver and Kidney Using a Physiologically- Based Pharmacokinetic Model for Improved Human Risk Analysis

ABSTRACT This research has studied the uncertainties in a physiologically-based pharmacokinetic (PBPK) model that describes uptake, accumulation, and elimination of Pb in the human body and to estimate the model's parameters. The model's application required probabilistic Pb exposure to humans which was accomplished by determining Pb content in various food items and food consumption patterns in a rural site near Kanpur, India. The important model parameters that varied were excretion constants, KELI and KEKI (1/d), for elimination of Pb from liver and kidney. For estimating these parameters, the PBPK model's equations were reorganized by incorporating steady state conditions. Measured blood and urine Pb levels were used for estimating these parameters. A significant variability was observed in estimated parameters, KELI (0.112 to 0.248/day) and KEKI (0.390 to 0.794/day). This research suggested that excretion parameters must be taken in a stochastic sense for obtaining proper estimates of human risk. In addition to KELI and KEKI, variability (food quantity, Pb concentration in food items, and bodyweight) was considered for estimating blood Pb concentrations through PBPK modeling and Monte-Carlo simulation. It was demonstrated that by not considering the variability, health risk was underestimated (compare 8.98 × 10−5 [no variability] to 9.34 × 10−3 [with variability]).

Multi-trace element levels and arsenic speciation in urine of e-waste recycling workers from Agbogbloshie, Accra in Ghana

To understand human contamination by multi-trace elements (TEs) in electrical and electronic waste (e-waste) recycling site at Agbogbloshie, Accra in Ghana, this study analyzed TEs and As speciation in urine of e-waste recycling workers. Concentrations of Fe, Sb, and Pb in urine of e-waste recycling workers were significantly higher than those of reference sites after consideration of interaction by age, indicating that the recycling workers are exposed to these TEs through the recycling activity. Urinary As concentration was relatively high, although the level in drinking water was quite low. Speciation analysis of As in human urine revealed that arsenobetaine and dimethylarsinic acid were the predominant As species and concentrations of both species were positively correlated with total As concentration as well as between each other. These results suggest that such compounds may be derived from the same source, probably fish and shellfish and greatly influence As exposure levels. To our knowledge, this is the first study on human contamination resulting from the primitive recycling of e-waste in Ghana. This study will contribute to the knowledge about human exposure to trace elements from an e-waste site in a less industrialized region so far scantly covered in the literature.

Synthesis and In Vivo Lead Detoxification Evaluation of Poly-α,β-dl-aspartyl-l-methionine

To increase the metal selectivity of polyaspartic acid, a so-called green chelant, poly-α,β-dl-aspartyl-l-methionine (PDM) was synthesized as a novel lead chelating agent. The phosphoric acid (80%) catalyzed thermal poly condensation of dl-aspartic acid provided poly succinimide, which was amidated with l-methionine to form PDM (MW: 29161). At the doses of 0.1, 1.0, and 10.0 nmol/kg, either by intraperitoneal injection (i.p.) or oral administration, PDM removed Pb from the spleens, hearts, and kidneys of mice, especially dose-dependently decreasing the accumulation of Pb in the brains, livers, and femurs of the mice, and did not interfere with the essential metals, including Cu, Fe, Mn, and Ca. Even at the dose of 0.1 nmol/kg, the i.p. injection of PDM removed Pb from the spleens, hearts, and kidneys of mice and increased the amount of urinary volume and urinary Pb, and the amount of fecal matter and the amount of fecal Pb, resulting in effective removal of Pb from the body of mice given Pb by i.p. injection. Our findings revealed that in aqueous solution PDM formed diverse nanospecies.

Lead concentration in feces and urine of exposed rats by x‐ray fluorescence and electrothermal atomic absorption spectrometry

Measurements made in feces and urine of Wistar rats exposed to lead acetate (n = 20) in drinking water since the fetal period were compared with those obtained from a control group (n = 20) in order to assess the age influence on Pb excretion. The measurements were made in different collections of rats aging between 1 and 11 months. To determine the Pb content of the samples, total reflection X‐ray fluorescence (TXRF) and electrothermal atomic absorption spectrometry (ETAAS) were used for the urine samples and energy dispersive X‐ray fluorescence (EDXRF) was used for the feces.The results show high concentrations of Pb being eliminated from the organism by urine and feces in contaminated rats. Values vary from (600 ± 140) µg l−1 to (5 460 ± 115) µg l−1 in urine and from (4 500 ± 300) µg g−1 to (11 400 ± 3 300) µg g−1 in dry feces. The control rats show, in general, low lead concentrations or below detection limits. The fecal/urinary ratio was studied. It was shown to be about three to four orders of magnitude and positively correlated with time. It was verified in feces and urine that excretion decreases with the animal age and that this decrease is made by different levels of excretion. The excretions of Pb in urine and in feces are positively correlated.A good agreement was found between the results obtained with TXRF and ETAAS for urine samples. This work also stresses the suitability of these techniques in the study of Pb intoxication. Copyright © 2011 John Wiley &amp; Sons, Ltd.

Effects of duration of exposure to dietary lead on rumen metabolism and the accumulation of heavy metals in sheep

The duration of exposure of sheep to dietary Pb may affect their ability to manage the toxic effects of the Pb, as well as influencing the metabolism of other heavy metals. Sheep were exposed to a supplement of 34mg Pb/kg basal diet DM for 3, 6 or 9 weeks. Compared with 3-week exposure, rumen contents after 6 weeks had increased Pb content (P=0.02), and after 9 weeks had reduced Cu (P=0.01) and Cr (P=0.04) concentrations. The longer exposure periods reduced digestion of long particles, and increased the alkali buffering potential in the rumen, but duration of exposure to Pb did not affect its proportional absorption (P=0.26). Most additional Pb was excreted in faeces or accumulated in the bones and spleen, and urinary Pb output was increased (P<0.01) after exposure for 6 or 9 weeks. Proportional absorption of Cd was increased after 6 and 9 weeks of Pb exposure, compared to 3 weeks (P<0.01), and after 6 weeks renal Cd had increased from 4 to 9mg/kg (P<0.01), which is above the normally accepted legal maximum concentration of 4.8mg/kg. After 9 weeks of Pb exposure Cd had declined in the kidney and increased in blood cells. It is concluded that duration of exposure to Pb did not affect its absorption, and there was no evidence of protective mechanisms, but extended exposure caused increased accumulation of Cd that rendered renal concentrations above legal limits.

The association between total urinary arsenic concentration and renal dysfunction in a community-based population from central Taiwan

Arsenic (As) is an important environmental toxicant that can cause cancer and cardiovascular disease, but the relationship between As exposure and renal dysfunction is not clear. The aim of this study is to examine the association between As exposure and renal dysfunction in a community-based population in central Taiwan. One thousand and forty-three subjects were recruited between 2002 and 2005. The risk for type 2 diabetes was increased by 2-fold (p<0.05) in subjects with total urinary As (U-As)>75μgg−1 creatinine as compared with subjects whose U-As was ⩽35μgg−1 creatinine after the adjustment for potential confounders. The adjusted odds ratio for an abnormal β2 microglobulin (B2MG>0.154mgL−1) was significantly higher in subjects with U-As>35μgg−1 creatinine as compared with the reference group adjusted for age, sex, living area, cigarette smoking, diabetes, and hypertension. The risk for abnormal B2MG and estimated glomerular filtration rate (eGFR<90mL min−1(1.73m2)−1) was both increased around 2-fold (p<0.05) in subjects with U-As>75μgg−1 creatinine as compared with those with U-As⩽35μgg−1 creatinine adjusted for all the risk factors plus lead (Pb), cadmium and nickel. The prevalence of abnormal B2MG was 4.82 times higher in subjects with both over the median levels of U-As (85.1μgL−1) and urinary Pb (18.9μgL−1) as compared to both lower than the median (p<0.001). These results indicate that U-As might relate to renal dysfunction even other important risk factors were taken into account. Follow-up studies for causal inference are warranted.

Metal Exposure for Residents Near Diesel Transport Routes

For the past few years, a large number of diesel vehicles carrying gravel and sand have shuttled back and forth every day on the main route (Tai-16 and Tai-21 highways) from Shuili to Shinyi in Nantou County, Taiwan, in support of a river-dredging project. Five stations along Tai-16 and three stations along Tai-21 were selected as the exposure sites. Two very small villages located about 9 and 12 kilometers, respectively, away from the diesel transport routes were selected as the control sites. In this study, five exposure pathways, i.e., ingestion from drinking water, household dust, rice, non-rice dishes, and inhalation from airborne particles, were considered. The daily intake doses of metals varied significantly among the five exposure pathways. There was a significant difference between the exposure and control sites regarding the doses of metals obtained from the exposure pathways of household dust and aerosols. However, regarding the exposure pathways of rice, non-rice dishes, and drinking water, no significant difference between the exposure and the control sites was observed for most metals. Residents who lived within 30 meters of diesel transport roads at the exposure sites were selected as the exposure groups for urine sampling, while residents of the control sites were selected as the control groups. The metal concentrations in the urine of the exposure groups were all higher than those of the control groups. With regards to the urinary metals Fe, Pb, Cu, Ni, and Mo, the levels of urinary metals in residents and the daily intakes of metals from the five exposure pathways showed that the exposure pathways from environmental media (i.e., drinking water, aerosols, and household dust) were a greater factor than food pathways (i.e., rice and non-rice dishes) in the resulting comparative differences between urinary concentration levels of Fe, Pb, Cu, and Mo in exposure groups and control groups. However, the food exposure pathways, rather than the environmental pathways, led to greater comparative differences between the urinary concentration levels of Mn within the two groups.

Genotoxicity evaluation in workers occupationally exposed to lead

Lead (Pb) is a widely used heavy metal with a broad industrial usage. Nevertheless, Pb is a serious public health issue as it is one of the most widespread environmental and industrial toxins. The aim of this investigation was to assess the genotoxicity of Pb using the comet assay, micronucleus (MN) and chromosomal aberrations (CA) test. Blood and urinary Pb content, levels of delta-aminolevulinic acid dehydratase in the erythrocytes (E-ALAD) and delta-aminolevulinic acid in urine (U-ALA) were determined. The exposure associated oxidative stress was also studied. The study group comprised of 90 male Pb recovery unit workers and 90 matched controls. The results indicated that the exposed workers had a significantly higher mean comet tail length than that of controls (P<0.05). Analysis of micronuclei in buccal epithelial cells (BEC's) and peripheral blood lymphocytes (PBL) revealed that there was a significant increase in frequency of MN in exposed subjects than controls. The frequency of aberrant metaphases was also found to be significantly elevated in the Pb exposed workers. The levels of antioxidant enzymes were relatively reduced (P>0.05) while the rate of lipid peroxidation was higher in the exposed subjects. Blood and urinary Pb concentrations were found to be higher in exposed workers than in controls. E-ALAD levels were reduced and U-ALA levels were elevated in the exposed subjects in comparison to controls. Results of analysis, taking the confounding factors into consideration provide evidence for the association of Pb exposure and genotoxicity, and predict the increased risk of cancer to the exposed workers. In view of the observed results, it can be strongly concluded that the workers comprise the risk group and adequate safety, precautionary and preventive measures could only minimize exposure and the related health hazards.

Protective effect of N-acetylcysteine on experimental chronic lead nephrotoxicity in immature female rats

Oxidative stress plays a key role in lead (Pb)-induced nephrotoxicity. N-acetylcysteine (NAC) is a potent oxygen free radicals scavenger and a metal chelator. In the present study, female Sprague-Dawley rats received PbAc(2) (300 mg/L, via drinking water) and/or NAC (100 mg/kg/day, by intraperitoneal injection) to investigate the protective effect of NAC on Pb-induced renal damage and oxidative stress as well as its mechanism of action. Renal toxicity was evaluated by measuring urinary excretion of total protein, beta(2)-microglobulin, albumin and urinary enzyme markers of tubular necrosis, as well as serum urea nitrogen level. Activities of antioxidant enzymes, contents of glutathione and malondialdehyde in kidney were also measured. Renal cell damage was assessed by electron microscopy. Animals that received both Pb and NAC showed a better renal function than those receiving Pb alone. Lead-induced tubular lesions and mitochondrial damage were markedly reduced in rats that also received NAC. Also, NAC significantly reduced the levels of lipid peroxidation and markedly restored the enzymic and non-enzymatic antioxidants levels in kidney of Pb-treated rats. Moreover, NAC administration significantly increased urinary Pb excretion and decreased its level in the serum and kidney. In conclusion, NAC treatment prevents renal tubular damage induced by chronic Pb administration, most probably through its antioxidant properties and chelating ability.