environmental exposure to lead and its correlation with biochemical indices in children

8
Environmental exposure to lead and its correlation with biochemical indices in children M. Ahamed a , S. Verma b , A. Kumar b , M.K.J. Siddiqui a, * a Analytical Toxicology, Industrial Toxicology Research Centre, P.O. Box-80, M.G. Marg, Lucknow-226 001, India b Department of Paediatrics, King George’s Medical University, Lucknow, India Received 3 August 2004; accepted 1 December 2004 Available online 30 January 2005 Abstract Lead is a global concern because of its ubiquity in the environment and known to be associated with abnormal neurobehavioral and cognitive development of young children. There is no study from India to describe a composite profile of blood lead and its biochemical influences in children. The present study was aimed at determining the proportion of children with N10 Ag/dL blood lead levels (BLLs), association between BLLs, and sociodemographic characteristics, if any, and alterations in biochemical indices in the blood as an underlying mechanism of lead intoxication. A total of 62 children (4–12 y) of Lucknow and nearby areas were recruited to determine BLLs, y-amimolevulinic acid dehydratase (y-ALAD) activity, catalase (CAT) activity, and malondialdehyde (MDA) and glutathione (GSH) levels in the blood. Mean level of blood lead was 7.47F3.06 Ag/dL (2.78–15.0) and 29%-exceeded 10 Ag/dL, CDC intervention level. The BLLs were found to be significantly influenced by social status, area of residence, source of water supply, maternal educational status ( p b0.001), type of house, and proximity to traffic density ( p b0.01). y-ALAD was significantly lower in the group of children with BLLs 11.39F1.39 Ag/dL when compared to children with BLLs 7.11F1.25 Ag/dL and 3.93F0.61 Ag/dL ( p =0.0007, 0.0005, respectively). However, CAT activity was higher in the groups of children with higher blood levels than with lower BLLs ( p =0.0159, 0.0001, respectively). There was an increase in MDA level with a concomitant decrease of GSH in children with BLLs 11.39F1.39 Ag/ dL compared with those of children with BLLs 7.11F1.25Ag/dL and 3.93F0.61 Ag/dL ( p =0.0001, 0.0002, and p =0.0001, respectively). There was statistically significant correlation of BLLs with y-ALAD (r =À0.44, p =0.00035), MDA (r =0.46, p =0.00018), GSH (r =À0.62, p =0.00001), and CAT (r =0.44, p =0.00035). Significantly, CAT activity, MDA, and GSH levels were in turn, found to be correlated with y-ALAD (r =À0.45, p =0.00024; r =À0.43, p =0.00053; r =0.43, p =0.00053, respectively). Results of the present study indicate a declining trend of BLLs in children when compared with those reported from metropolitan cities of India when leaded gasoline was in practice and that the BLLs were significantly associated with biochemical indices in the blood which have the potential to be used as biomarkers of lead intoxication. D 2005 Elsevier B.V. All rights reserved. Keywords: Environmental exposure; Lead; Atomic Absorption Spectrophotometer; y-ALAD; Oxidative stress; Biomarkers 0048-9697/$ - see front matter D 2005 Elsevier B.V. All rights reserved. doi:10.1016/j.scitotenv.2004.12.019 * Corresponding author. Tel.: +91 522 2227586. E-mail address: [email protected] (M.K.J. Siddiqui). Science of the Total Environment 346 (2005) 48– 55 www.elsevier.com/locate/scitotenv

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  • influenced by social status, area of residence, source of water supply, maternal educational status ( pb0.001), type of house, and

    Keywords: Environmental exposure; Lead; Atomic Absorption Spectrophotometer; y-ALAD; Oxidative stress; Biomarkersproximity to traffic density ( pb0.01). y-ALAD was significantly lower in the group of children with BLLs 11.39F1.39 Ag/dLwhen compared to children with BLLs 7.11F1.25 Ag/dL and 3.93F0.61 Ag/dL ( p=0.0007, 0.0005, respectively). However,CAT activity was higher in the groups of children with higher blood levels than with lower BLLs ( p=0.0159, 0.0001,

    respectively). There was an increase in MDA level with a concomitant decrease of GSH in children with BLLs 11.39F1.39 Ag/dL compared with those of children with BLLs 7.11F1.25Ag/dL and 3.93F0.61 Ag/dL ( p=0.0001, 0.0002, and p=0.0001,respectively). There was statistically significant correlation of BLLs with y-ALAD (r=0.44, p=0.00035), MDA (r=0.46,p=0.00018), GSH (r=0.62, p=0.00001), and CAT (r=0.44, p=0.00035). Significantly, CAT activity, MDA, and GSH levelswere in turn, found to be correlated with y-ALAD (r=0.45, p=0.00024; r=0.43, p=0.00053; r=0.43, p=0.00053,respectively). Results of the present study indicate a declining trend of BLLs in children when compared with those reported

    from metropolitan cities of India when leaded gasoline was in practice and that the BLLs were significantly associated with

    biochemical indices in the blood which have the potential to be used as biomarkers of lead intoxication.

    D 2005 Elsevier B.V. All rights reserved.Environmental exposure to lead and its correlation with

    biochemical indices in children

    M. Ahameda, S. Vermab, A. Kumarb, M.K.J. Siddiquia,*

    aAnalytical Toxicology, Industrial Toxicology Research Centre, P.O. Box-80, M.G. Marg, Lucknow-226 001, IndiabDepartment of Paediatrics, King Georges Medical University, Lucknow, India

    Received 3 August 2004; accepted 1 December 2004

    Available online 30 January 2005

    Abstract

    Lead is a global concern because of its ubiquity in the environment and known to be associated with abnormal

    neurobehavioral and cognitive development of young children. There is no study from India to describe a composite profile of

    blood lead and its biochemical influences in children. The present study was aimed at determining the proportion of children

    with N10 Ag/dL blood lead levels (BLLs), association between BLLs, and sociodemographic characteristics, if any, andalterations in biochemical indices in the blood as an underlying mechanism of lead intoxication. A total of 62 children (412 y)

    of Lucknow and nearby areas were recruited to determine BLLs, y-amimolevulinic acid dehydratase (y-ALAD) activity,catalase (CAT) activity, and malondialdehyde (MDA) and glutathione (GSH) levels in the blood. Mean level of blood lead was

    7.47F3.06 Ag/dL (2.7815.0) and 29%-exceeded 10 Ag/dL, CDC intervention level. The BLLs were found to be significantly

    Science of the Total Environment 346 (2005) 4855

    www.elsevier.com/locate/scitotenv0048-9697/$ - s

    doi:10.1016/j.sc

    * Correspondin

    E-mail addreee front matter D 2005 Elsevier B.V. All rights reserved.

    itotenv.2004.12.019

    g author. Tel.: +91 522 2227586.

    ss: [email protected] (M.K.J. Siddiqui).

  • examinations, socioeconomic status, and educational

    levels of parents as given in Table 1 were recorded.

    Tota1. Introduction

    Lead is an environmental menace and children are

    more susceptible to lead than adults because of their

    hand to mouth activity, increased respiratory rates,

    and higher gastro-intestinal absorption per unit body

    weight (WHO/IPCS, 1995; Jarosinska et al., 2004).

    Adult absorb 3550% of lead that they ingest as

    against greater than 50% by the children (Ellenhorn,

    1997). It is well known that 90% body burden of lead

    is deposited in bone, which can leach out during

    growth and development of children constituting a

    significant long-term source of lead in the blood

    (Mahaffey et al., 2000). Mobilization of maternal lead

    from bone during pregnancy and lactation (Silbergeld,

    1991), together with environmental exposure

    increases the body burden of lead in children. Major

    sources of environmental lead exposure are leaded

    gasoline, leaded pipes for water supply, lead based

    paints, use of leaded ceramics, and lead in cosmetics,

    and folk remedies (Fewtrell et al., 2004). Distance of

    residence from traffic density, ethnicity, housing, poor

    nutrition, low maternal education, and socioeconomic

    status are the factors further influencing blood lead

    levels in children (von Schirnding et al., 1991;

    Mahaffey, 1995; Baghurst et al., 1999; Mathee et

    al., 2002; Diouf et al., 2003).

    Exposure to lead can result in significant alter-

    ations in multiple organs, with hematological system

    being important target. Inhibition of y-aminolevulinicacid dehydratase (y-ALAD), the second enzyme in theheme biosynthesis pathway catalyzing the condensa-

    tion of two molecules of y-aminolevulinic acid (y-ALA) to a porphobilinogen (PBG) by organic and

    inorganic lead (Goering, 1993; Sakai and Morita,

    1996; Goyer and Clarkson, 2001; Gurer-Orhan et al.,

    2004) is a biochemical indicator of lead toxicity

    resulting in the accumulation of delta-ALA that can be

    fastly oxidized to generate reactive oxygen species

    (ROS) as superoxide ion (O2), hydroxyl radical

    (OH), and hydrogen peroxide (H2O2) (Hermes-Limaet al., 1991; Stohs and Bagchi, 1995; Bechara, 2004).

    As a consequence, enhanced lipid peroxidation

    (LPO), DNA damage, and altered calcium and

    sulfhydryl homeostasis may occur. Recent studies, in

    vitro (Neal et al., 1997; Hunaitic and Sound, 2000), in

    M. Ahamed et al. / Science of thevivo (Gurer et al., 1998), and among occupationally

    exposed workers (Sugawara et al., 1991; Jium andAll the subjects indicated that they were not occupa-

    tionally exposed to lead and none of the subjects were

    under any medication.

    2.2. Blood collection

    Parents of the children were explained about the

    study and their consent was obtained. Five milliliters

    of venous blood withdrawn from each subject,

    collected in preheparinized vials as coded samples,

    was transported under ice cold conditions to Depart-

    ment of Analytical Toxicology, Industrial Toxicology

    Research Centre (ITRC), Lucknow for lead analysis

    and other biochemical assays. An aliquot of hepari-

    nised blood was centrifuged at 3000 rpm; 4 8C for15 min and plasma was removed. RBCs collectedHsien, 1994) have shown lead induced oxidative

    damage suggesting that y-ALAD inhibition togetherwith oxidative stress parameters might be a biochem-

    ical tool to assess lead toxicity.

    There is no Indian study in children so far to

    describe together environmental exposure to lead

    and its association with biochemical indices that can

    be used as a predictive biomarker of lead into-

    xication. The present investigation was designed to

    determine proportion of children with blood lead

    N10 Ag/dL, and correlation of blood lead withsociodemographic characteristics and biochemical

    alterations resulting from environmental exposure

    to lead in children. The study is first of its kind from

    India that can be of wider environmental and

    societal importance.

    2. Materials and methods

    2.1. Subjects

    We studied a total of 62 randomly selected children

    (412 y) drawn from Lucknow, the capital of most

    populous state in Uttar Pradesh (UP), in India, and

    adjoining areas. Detailed case histories of all the

    children including gender, age, potential sources of

    lead in environment, area of residence, clinical

    l Environment 346 (2005) 4855 49were washed with normal saline, thee times, and

    again centrifuged for separation to be used for

  • en

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    TotaTable 1

    Blood lead levels and sociodemographic characteristics of the childr

    Variables No. of

    Children (412 y) 62 (100

    Gender Boys 55 (88.7

    Girls 7 (11.2

    Social status High 8 (12.9

    Middle 32 (51.6

    Low 22 (35.4

    Area of living Rural 26 (41.9

    Urban 36 (58.0

    Type of house Pucca 32 (51.6

    Mixed 14 (22.5

    Kachha 16 (25.8

    Source of water HP/Well 27 (43.5

    C. supply 35 (56.4

    Traffic/highway near residence b1 km 6 (9.6812 km 36 (58.0

    N2 km 20 (32.2Mothers education Illiterate 15 (24.1

    10th 11 (17.7

    M. Ahamed et al. / Science of the50determination of catalase activity (CAT). Remaining

    sample of whole blood was utilized for assays of y-ALAD, MDA, GSH, and biomonitoring of lead.

    Person analyzing the lead and carrying out bio-

    chemical assays was totally blind as to the case

    history of the subjects.

    2.3. Analysis of lead

    Blood lead was determined using a graphite

    furnace atomic absorption spectrometer (Varian Spec-

    trAA 250+, Varian Australia Pty, Victoria, Australia)

    (Khullar, 1999). The instrument was calibrated using

    aqueous standards of lead 10, 20, 30, and 40 Ag/L.Detection limit was 3 Ag/L. Fifty microliters of bloodwas diluted 1:10 in the diluent in a 1.0 mL

    polystyrene autosampler tube. The diluent (Triton X-

    100, 0.1% w/v); NH4H2PO4 0.2% (w/v); NH3 0.14

    (mol/L) was prepared in deionized water. The

    calibration blank used was 0.2% nitric acid, 0.2%

    12th 29 (46.77)

    G/higher 7 (11.29)

    S.D.: standard deviation; C. supply: Corporation supply; km: kilometer; H

    Statistically significant: ** pb0.001, * pb0.01.Pucca house: made up of concrete and cement, and painted walls and do

    Kachha house: made up of soil and wood.

    Mixed house: some part of house made up of cement and concrete, and p

    HP: ground water drawn through handpipe or well.

    C. supply: municipal corporation water, supplied to the community, is drawes (%) Blood lead levels meanFS.D. Range

    7.47F3.06 2.7815.007.60F3.15 3.458.866.54F2.31 2.7815.003.85F0.79 3.125.616.52F2.26 2.7812.7210.19F2.33TT 5.3615.005.41F2.32 2.7812.728.92F2.66TT 4.1215.008.72F2.99T 3.1215.005.97F2.59 3.2812.726.32F2.64 3.1410.185.61F2.44 2.7812.728.92F2.72TT 4.1215.0010.17F2.29T 7.212.128.04F2.99 3.1215.005.66F2.42 2.7812.728.50F2.37 4.6612.7210.25F2.78TT 5.4015.00

    l Environment 346 (2005) 4855NH4H2PO4 solution and reagent blank was diluent

    solution. Accuracy and precision of the method were

    checked by spiking the samples with known amounts

    of standard. Coefficients of variation were 6% and 4%

    at 10 and 40 Ag/dL, respectively.The accuracy of the method for metal estimation

    was further controlled by participation in an inter-

    laboratory quality-assurance programme (ITRC, Luck-

    now) wherein coded samples were analyzed regularly

    and results scrutinized by the quality manager. Further,

    a quality check sample was always run with each set of

    samples for lead analysis to maintain accuracy.

    2.4. Biochemical assays

    The European standardized method was used to

    determine the blood y-ALAD activity (Berlin andSchaller, 1974). Blood malondialdehyde (MDA)

    concentrations were determined by the method of

    Stocks and Dormandy (1971). For the determination

    6.30F2.77 2.7811.985.82F2.67 3.1510.18

    P: Handpipe; G: Graduation.

    ors.

    ainted while rest of the house is made up of soil and wood.

    n from Gomti river (after being processed in water treatment plant).

  • ed children

    27)

    G IIIBLLs 10.115

    (11.39F1.39) (n=18)p-value

    GI vs. GII

    p-value

    GII vs. GIII

    p-value

    GI vs. GII

    0) 7.89F1.89 (512) 0.8571 0.5572 0.65373.26F1.14 0.4948 0.0007T 0.0005T

    MDA meanFS.D. 16.51F4.51 14.96F5.65 24.74F6.83 0.3453 0.0001T 0.0002T13.71F4.89 0.1332 0.0001T 0.0001T94.70F17.26 0.0159T 0.0521 0.0001T

    : Amocant.

    Total Environment 346 (2005) 4855 51of glutathione (GSH) concentration in blood, 5,5V-dithiobis-(2-nitrobenzoic acid) (DTNB) was used as

    described by Kuo et al. (1983). Catalase (CAT)

    activity was determined by the method of Sinha

    (1972) using hydrogen peroxide (H2O2) as a substrate.

    Hemoglobin content in the hemolysate was measured

    by Drabkin and Austin (1932) method.

    2.5. Statistical analysis

    As given in Table 2, children were categorized into

    three groups, first group had BLLsb5 Ag/dL(3.93F0.61), second 510 Ag/dL (7.11F1.25), andthird group 10.115 Ag/dL (11.39F1.39). Students t-test was used to compare mean values of blood lead,

    y-ALAD, MDA, GSH, and CAT of the first group ofchildren with the second and third groups. The second

    group of children also compared with the third group.

    Students t-test was also used to compare two groups

    of different characteristics of children as given in

    Table 1. One-way ANOVA was applied to test the

    significance when comparing the social status, type of

    GSH meanFS.D. 26.73F8.71 23.21F6.51CAT meanFS.D. 63.35F21.35 81.44F24.34

    S.D.: standard deviation; Age: year; Blood lead level: Ag/dL; ALADCAT: 104 Amol H2O2 decomposed/min/gHb. * Statistically signifiTable 2

    Blood lead levels and biochemical indices of environmentally expos

    Variables G IBLLs b5(3.93F0.61) (n=17)

    G IIBLLs 510

    (7.11F1.25) (n=

    Age meanFS.D. (range) 7.47F1.91 (410) 7.57F1.70 (41y-ALAD meanFS.D. 4.82F1.25 4.56F1.20

    M. Ahamed et al. / Science of thehouse, traffic/highway near residence, and mothers

    education as these variables involved the comparison

    of more than two groups. Linear regression analysis

    was performed to determine the relationship between

    blood lead levels and biochemical indices.

    3. Results

    3.1. Blood lead levels and sociodemographic

    characteristics of the children

    A total of 62 children (55 boys and 7 girls, 412 y)

    were involved in the study. Their BLLs was7.47F3.06 Ag/dL (2.7815.0). Fig. 1 indicated that27% children had BLLsb5 Ag/dL, 44% had 510 Ag/dL, and 29% had 10.115 Ag/dL i.e. NCDC inter-vention level (CDC Atlanta, 1991). As given in Table

    1, BLLs were significantly higher among the children

    with low maternal educational levels and socio-

    economic status, living in urban areas, and drinking

    water of corporation supply compared to their

    counterparts ( pb0.001). Type of house and distanceof residence from traffic density were found to be

    significantly related to childrens BLLs ( pb0.01).

    3.2. Blood lead levels and biochemical indices

    As can be seen in Table 2, mean age of all three

    groups of the children was not significantly different.

    Blood y-ALAD activity was significantly lower in thethird group when compared with that of the first

    ( p=0.0005) and second group ( p=0.0007) of children.

    However, the difference in the y-ALAD activitybetween the first and second group was not significant

    statistically (Table 2). Blood MDA levels were

    l ALA/min/L blood; MDA: nmol/mL blood; GSH: Amol/mL blood;significantly higher ( p=0.0002, 0.0001) while GSH

    contents were significantly lower ( p=0.0001) in

    children who had BLLs 10.115 Ag/dL (11.39F1.39)

  • when compared with children of b5 Ag/dL (3.93F0.61)and 510 Ag/dL (7.11F1.25), respectively. Again thedifference in MDA and GSH levels between the first

    and second groups was not significant (Table 2).

    Blood CAT activity was also significantly higher in

    the third group than in the first ( p=0.0001).

    Similarly, activity was significantly different between

    group first and second ( p=0.0159). However, CAT

    activity was not different statistically between the

    second and third group (Table 2).

    3.3. Relationship between blood lead levels and

    oxidative stress parameters

    had above the CDC intervention level. The average

    BLL from these metropolitan cities in India is not

    M. Ahamed et al. / Science of the Tota52Table 3 represents the strength of relationship

    between BLLs and oxidative stress parameters. BLLs

    were significantly correlated with blood y-ALAD,MDA, GSH, and CAT activity; BLLs-blood y-ALADactivity (r=0.44, p=0.00035), BLLs-blood MDA(r=0.46, p=0.00018), and BLLs-blood GSH

    (r=0.62, p=0.00001) and BLLs-blood CAT activity(r=0.44, p=0.00035).

    3.4. Relationship between blood d-ALAD andoxidative stress parameters

    Table 3 also indicates the correlation between

    blood y-ALAD activity, as a clinical biomarker of leadtoxicity, and oxidative stress parameters. Blood y-ALAD activity was found to be significantly corre-

    lated with blood MDA (r=0.43, p=0.00053), bloodGSH (r=0.43, p=0.00053), and blood CAT activity

    (r=0.45, p=0.00024), suggesting the possibility of

    Table 3

    Correlation of blood lead concentrations and y-ALAD withoxidative stress parameters in environmentally exposed children

    Pb y-ALAD MDA GSH CAT

    Pb 1 0.44a 0.46b 0.62c 0.44ay-ALAD 1 0.43d 0.43d 0.45eMDA 1

    GSH 1

    CAT 1

    All correlation coefficients (r) are statistically significant.a p=0.00035.b p=0.00018.c p=0.00001.

    d p=0.00053.e p=0.00024.reported (George, 1999). Recent studies from Johan-

    nesburg (Mathee et al., 2002), Senegalese (Diouf etthe potential use of these oxidative stress parameters

    as biomarkers of lead intoxication.

    4. Discussion

    Lead impregnation in children has declined

    significantly in many developed countries following

    withdrawal of leaded gasoline (Inserm, 1999; Grosse

    et al., 2002). Some of the developing countries like

    China and Poland too have reported an appreciable

    downward trend in the body burden of lead in their

    population as part of measures enforced to curb one

    of the biggest environmental problem of the world

    (Wang et al., 2000; Jarosinska et al., 2004). Yet, the

    extent and real magnitude of problem associated with

    environmental exposure to lead to its rapidly grow-

    ing population in India have neither been duly

    emphasized nor systematically studied to generate a

    base-line data. There is paucity of data especially,

    from northern region of the country both on BLLs in

    different age group of children and its possible

    biochemical interaction. The sampling site of the

    present study is Lucknow, the capital of the most

    populous state Uttar Pradesh in India and the results

    highlighted the mean BLL 7.47 Ag/dL among thechildren which is b10 Ag/dL, CDC interventionlevel. However, 29% of the children still had N10Ag/dL (Fig. 1). When these data are compared withBLLs determined by us among the newborns (11.40

    Ag/dL) in Lucknow during the year 2000 whenleaded gasoline was in practice (Srivastava et al.,

    2001) and 54% newborns then exceeded the inter-

    vention level it appears that there is decline in BLLs

    since unleaded gasoline came into being in the

    region in 2000 (Envis, ITRC 2001). Further, a

    comparison of the present data with those of

    Mumbai, Bangalore, Kolkata, Chennai, Hyderabad,

    and Delhi where respectively 42%, 42%, 87%, 96%,

    43%, 95% children (of those participated) exceeded

    CDC intervention level of N10 Ag/dL again suggestsa declining of BLLs in Lucknow where only 29%

    l Environment 346 (2005) 4855al., 2003), Taiwan (Wang et al., 2000), and USA

    (Inserm, 1999) reported respectively 11.90 Ag/dL,

  • Tota8.34 Ag/dL, 5.50 Ag/dL, and 3.6 Ag/dL blood lead intheir children. However, keeping in view the fact that

    there is no safe level of blood lead in children

    (Schwartz, 1994; Lanphear et al., 2000) efforts are

    still required to contain other sources of environ-

    mental exposure to lead.

    In the present study, BLLs in children were sig-

    nificantly influenced by socioeconomic status and

    maternal educational levels ( pb0.001) (Table 1).Studies conducted in other countries also have shown

    low socioeconomic status and maternal educational

    levels as risk factors that significantly influenced the

    BLLs during childhood (von Schirnding et al., 1991;

    Baghurst et al., 1999; Mathee et al., 2002; Wang et al.,

    2000). The higher BLLs in such children might be due

    to illiterate/lower educated mothers being unaware

    about different sources of lead in environment and

    subsequently its impact on childrens health leading to

    lack of any preventive measures at individual level.

    Poor nutrition of children belonging to low socio-

    economic status may also increase their susceptibility

    to lead. As can be seen in Table 1, mean level of blood

    lead in urban children was significantly higher than

    rural ones ( pb0.001). Diouf et al. (2003) also foundsimilar results, supporting our findings. Higher BLLs

    in urban children could be due to higher automobile

    exhaust, and presence of lead based factories and

    workshops that contaminate urban environment.

    Moreover, most of the urban population uses corpo-

    ration supplied water and lives in pucca painted

    house. Lead based paints and corporation supplied

    water contribute substantial amount of lead in child-

    rens blood (Pirkle et al., 1994; Lanphear et al., 1996).

    Further, children using corporation supplied water

    have higher BLLs ( pb0.001) than children usingwater of hand pipe/well in the present study (Table 1).

    Pirkle et al. (1994) also found a substantial decline of

    BLLs in children after removal of lead from municipal

    water. Ryan et al. (2004) stated paints, drinking water,

    soil, and dust that contain lead are the good sources of

    lead exposure after phasing out of leaded gasoline

    besides lead smelters and industrial processes. In

    Lucknow, municipal corporation water supplied to

    communities is drawn from Gomti river (after being

    processed in water treatment plant) which gets

    exposed to lead through discharge of lead smelting

    M. Ahamed et al. / Science of thefactories, workshops, and other social activities.

    Moreover, corporation supplied water runs throughlead solded old pipes that further increases the

    concentration of lead in water. Higher BLLs in

    children living in pucca painted house ( pb0.01) thanthose living in mixed and kachha house (Table 1)

    again emphasize that paints are the chief sources of

    lead besides dust in pucca houses. On the basis of

    gender, we did not notice a significant difference

    between BLLs in girls and boys (Table 1) as reported

    by Mathee et al. (2002) and Wang et al. (2000)

    wherein boys had higher blood lead than girls.

    The hematological system has been proposed as

    being an important target of lead-induced toxicity and

    RBCs with a high affinity for lead typically contain a

    majority of the lead found in the blood stream

    (Leggett, 1993). Several factors such as high concen-

    tration of oxygen, autooxidizability of hemoglobin,

    vulnerable membrane components to lipid peroxida-

    tion, and limited capacity to repair their damaged

    components make RBCs sensitive to oxidative dam-

    age (Rice-Evans, 1990; Adonaylo and Otieza, 1999).

    The inhibitory effect of both organic and inorganic

    lead on y-ALAD accounts for accumulation of y-ALAthat has been shown to undergo metal catalysed

    autooxidation to generate ROS (Hermes-Lima et al.,

    1991; Bechara, 2004; Oteiza et al., 1995). In the

    presence of ROS, GSH is rapidly oxidized to GSSG

    resulting in a decrease in GSH content. Higher

    production of ROS leads to increased membrane lipid

    peroxidation with a concomitant decrease in antiox-

    idants like GSH and activity of antioxidant enzymes

    such as CAT also increases to scavenge these free

    radicals (Sugawara et al., 1991; Jium and Hsien,

    1994). This appears to be the underlying mechanism

    of lead induced oxidative stress. Sakai and Morita

    (1996) found that threshold value of blood lead for y-ALAD inhibition was extremely low (around 5 Ag/dL), as against those we found in the present study

    together with an increase in MDA level and a

    concomitant decline in GSH (Table 2). Evidence for

    lead induced oxidative stress in the present study also

    arises from the significant increase in the CAT activity

    in groups of children with higher BLLs compared to

    those with lower BLLs (Table 2). Catalase has been

    suggested to provide an important pathway for H2O2decomposition at higher steady state H2O2 concen-

    trations, where glutathione peroxidase is believed to

    l Environment 346 (2005) 4855 53play a more important role in H2O2 decomposition

    under lower steady state levels of H2O2 (Michiels et

  • Estimation of global burden disease of mild mental retardation

    and cardiovascular diseases from environmental lead exposure.

    Totaal., 1994). Increased catalase activity can be explained

    as a defense mechanism of red blood cells against

    increased fluxes of H2O2 during lead induced

    oxidative stress. Enhanced lipid peroxidation

    (increase in MDA) and CAT activity together with

    depletion of GSH in the present study suggest the

    possible contribution of lead induced oxidative stress

    in children through inhibition of y-ALAD, accumu-lation of y-ALA that triggers the process of oxidativestress. Similar findings were observed in vitro (Neal et

    al., 1997; Hunaitic and Sound, 2000), in vivo (Gurer

    et al., 1998), and among occupationally exposed

    workers (Sugawara et al., 1991; Jium and Hsien,

    1994).

    In the present study, BLLs were found to have

    significant negative correlations with y-ALAD(r=0.44) and GSH (r=0.62), and positive correla-tions with MDA (r=0.46) and CAT (r=0.44). In turn,

    y-ALAD had significant negative correlations withMDA (r=0.43) and CAT (r=0.45), and positivecorrelation with GSH (r=0.43). The strength of these

    associations in the backdrop of studies on the effect of

    lead on the parameters of oxidative stress (Tandon et

    al., 2002) and in vitro data (Neal et al., 1997) related

    to interaction of blood lead with blood y-ALAD,MDA, CAT, and GSH/GSSG ratio activity opens up

    the possibility of the use of these biochemical targets

    as biomarkers of effect due to lead exposure. These

    biochemical markers have also been shown to be

    altered among the workers occupationally exposed to

    lead (Jium and Hsien, 1994). To what extent these

    biomarkers can replace the biomonitoring of lead and/

    or y-ALAD measurement as bioindicator of exposureto lead is a matter of further investigation. However,

    non-specificity of these parameters to lead and their

    modulation by other environmental/chemical stresses

    needed to be taken care of in the event of their

    potential application.

    Since, subjects in the study did not report any

    occupational or accidental exposure to lead, the

    source of lead as detected may be environmental

    only and the regulatory agencies are expected to be

    watchful to enforce measures to control/mitigate

    other sources of environmental exposure to lead like

    recycling of batteries and their use in electronic

    industries. Further studies in India are warranted to

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    Environmental exposure to lead and its correlation with biochemical indices in childrenIntroductionMaterials and methodsSubjectsBlood collectionAnalysis of leadBiochemical assaysStatistical analysis

    ResultsBlood lead levels and sociodemographic characteristics of the childrenBlood lead levels and biochemical indicesRelationship between blood lead levels and oxidative stress parametersRelationship between blood delta-ALAD and oxidative stress parameters

    DiscussionAcknowledgmentReferences