Delta-aminolevulinic acid dehydratase inhibition and oxidative stress in relation to blood lead among urban adolescents

Abstract

To explore lead-induced oxidative stress among urban adolescents, the present study, the first from India, was designed to determine the proportion of urban adolescents with blood lead > 10 μg/dL and its impact on selected oxidative stress parameters and delta-aminolevulinic acid dehydratase (δ-ALAD) inhibition, which could be used as biomarkers of lead intoxication. A total of 39, urban, male adolescents, drawn from Lucknow and adjoining areas, were recruited to determine lead, d-ALAD, malondialdehyde (MDA) and glutathione (GSH) in blood and catalase (CAT) in RBCs. Mean level of blood lead was 9.96 ± 3.63 μg/dL (4.62 - 18.64); 43% of adolescents crossed the Centre for Disease Control (CDC) intervention level of 10 mg/dL blood lead. On the basis of blood lead levels (BLLs), adolescents were categorized into two groups: Group I and Group II had a blood lead < 10 μg/dL (7.40 ± 1.62) and < 10 μg/dL (13.27 ± 2.67), respectively, with significantly different mean values (P < 0.001). Age, sex, body mass index (BMI), Hb level (malnutrition), and area of living as confounders of lead exposure and toxicity were not statistically different between the two groups. However, d-ALAD activity was significantly lower (P < 0.001), while CAT activity was higher in Group II than in Group I (P < 0.01). MDA level was also significantly higher in Group II compared to Group I (P < 0.001). There were significant negative correlation of BLL with d-ALAD (r = -0.592, P < 0.001), and positive correlations with CAT (r= -0.485, P < 0.01) and MDA (r = -0.717, P < 0.001). Interestingly, d-ALAD, in turn, had significant negative correlations with CAT (r = -0.456, P <0.01) and MDA (r = -0.507, P < 0.01). Results of the present pilot study provide clues to the possible low level of lead-induced oxidative stress in urban adolescents, suggesting that lead-induced d-ALAD inhibition can also be an indicator of oxidative stress. The potential of oxidative stress parameters to be used as biomarkers of lead toxicity warranted further investigation.

Keywords

adolescents atomic absorption spectrometer biomarkers blood lead catalase δ-ALAD glutathione lipid peroxidation oxidative stress

References

Aronson JE , Smith AM , Kathori V. Elevated blood lead levels among internationally adopted children US 1998 . JAMA 2000; 283: 1416-1418 .

Mathee A , von Shirnding YER , Levin J , Ismail A , Hunteley R , Cantrell A. A survey of blood lead levels among young Johannesburg school children . Environ Res 2002; 90: 181-184 .

Diouf A , Garcon G , Thiaw C , Diop Y , Fall M , Ndiaye B , Siby T , Hannothiaux MH , Zerimech F , Ba D , Haguenoer JM , Shirali P. Environmental lead exposure and its relationship to traffic density among Senegalese children: a pilot study . Hum Exp Toxicol 2003; 22: 559-564 .

Jarosinska D , Peddada S , Rogan J. Assessment of lead exposure and associated health risk factors in urban children in Silesia, Poland . Environ Res 2004; 95: 133-142 .

Ramieu I , Palazazuelos E , Hernandes-Avila M. Sources of lead exposure in Mexico-city . Environ Health Perspect 1994; 102: 384-389 .

Shen X , Yan C , Zhang Y. Comparisons of children’s blood lead levels in Shanghai before and after the introduction of lead free gasoline . Nat Med J China 1999; 79: 739-741 .

Luo W , Zhang Y , Li H. Children’s blood lead levels after phasing out of leaded gasoline in Santou, China . Arch Environ Health 2003; 58: 184-187 .

Ryan JA , Berti WR , Brown SL , Casteel SW , Chaney RL , Hallfrisch J , Doolan M , Grevatt P , Maddaloni P , Mosby D. Reducing children’s risk from lead in soil . Environ Sci Technol 2004; 38: 19A-24A .

Fewtrell LJ , Pruss-Ustan A , Ladrigan P , Ayuso-Mateos JL. Estimation of global burden disease of mild mental retardation and cardiovascular diseases from environmental lead exposure . Environ Res 2004; 94: 120-133 .

10.

Envis Center, Industrial Toxicology Research Centre (ITRC) . Current status of lead in India. Released on World Environmental Day, 5 June, 2001. Retrieved from www.envisitrc.com

11.

Sugawara E , Nakamura K , Miyake T , Fukumura A , Seki Y. Lipid peroxidation and concentration of glutathione in erythrocytes from workers exposed to lead . Br J Ind Med 1991; 48: 239-242 .

12.

Costa CA , Trivelato GC , Pinto AMP , Bechara EJH. Correlation between plasma 5 -aminolevulinic acid concentrations and indicators of oxidative stress in lead-exposed workers . Clin Chem 1997; 43: 1196-1202 .

13.

Pande M , Flora SJS. Lead-induced oxidative damage and its response to combined administration of lipoic acid and succimers in rat . Toxicology 2002; 177: 187-196 .

14.

Gurer-Orhan H , Sabir HU , Ozgunes H. Correlation between clinical indicator of lead poisoning and oxidative stress parameters in controls and lead exposed workers . Toxicology 2004; 195: 147-154 .

15.

Hermes-Lima M , Pereira B , Bechara EJ.

Are free radicals involved in lead poisoning?

Xenobiotica 1991; 21: 1085-1090 .

16.

Hunaitic AA , Sound M. Effect of lead concentration and level of glutathione-S -transferase, reductase and peroxidase in human blood . Sci Total Environ 2000; 248: 45-50 .

17.

Tandon SK , Prasad S , Singh S , Shukla M , Chatterjee M. Influence of age on lead induced oxidative stress in rat . Biol Trace Elem Res 2002; 87: 1-10 .

18.

Ahamed M , Verma S , Kumar A , Siddiqui MKJ. Environmental exposure to lead and its correlation with biochemical indices in children . Sci Total Environ 2005; 346: 48-55 .

19.

Centre for Disease Control (CDC) . Preventing lead poisoning in young children. A statement by the CDC, October 1991. US Department of Health and Human Services .

20.

Berlin A , Schaller KN. European standardized method for determination of delta-ALAD activity in blood . Zeitsch Klin Chem Klin Biochem 1974; 12: 389-390 .

21.

Stocks J , Dormandy TL. Auto-oxidation of red cell lipids induced by hydrogen peroxide . Br J Hematol 1971; 20: 95-111 .

22.

Kuo CH , Maita K , Sleight SD , Hook JB. Lipid peroxidation: a possible mechanism of cephaloridine-induced nephrotoxicity . Toxicol Appl Pharmacol 1983; 67: 78-88 .

23.

Sinha AK. Colorimetric assay of catalase . Anal Biochem 1972; 47: 389-394 .

24.

Drabkin DL , Austin JH. Spectrophotometric studies: spectrophotometric constant for common hemoglobin derivatives in human, dog and rabbit blood . J Biol Chem 1932; 98: 719-719 .

25.

Khullar KD. Determination of lead in whole blood electrothermal atomic absorption spectrometry . Lab-news 1999; 4: 3-4 .

26.

Jium YS , Hsien LT. Lipid peroxidation in workers exposed to lead . Arch Environ Health 1994; 49: 256-259 .

27.

George AM. Proceeding of the International Conference of Lead Poisoning Prevention and Treatment: Implementing a National Programme in Developing Countries. George Foundation, Bangalore, India, February 8-10, 1999.

28.

Kaiser R , Henderson AK , Daley WR. Blood lead levels of primary school children in Dhaka, Bangladesh . Environ Health Perspect 2001; 109: 563-566 .

29.

Wang CL , Chung HY , Ho C , Yang CY , Tsai JL , Wu TS , Wu TN. Relationship between blood lead concentrations and learning achievement among primary school children in Taiwan . Environ Res Sec A 2000; 89: 12-18 .

30.

INSERM. Plomb dans l’environement quels risques pour la santhe? INSERM, 1999.

31.

Bergdahl IA , Grubb A , Schutz A , Desnick RJ , Wetmur JG , Sassa S , Skerfving S. Lead binding to delta-aminolevulinic acid dehydratase (ALAD) in human erythrocytes . Pharmacol Toxicol 1997; 81: 153-158 .

32.

Sakai T , Morita Y. Delta-aminolevulinic acid in plasma or whole blood as a sensitive indicator of lead effects, and its relation to the other heme-related parameters . Int Arch Occup Environ Health 1996; 68: 126-132 .

33.

Michiels C , Raes M , Toussaint O , Remacle J. Importance of S-glutathione peroxidase, catalase and Cu/Zn SOD for cell survival against oxidative stress . Free Rad Biol Med 1994; 17: 235-248 .

34.

Ye XB , Fu H , Zhu JL , Ni WM , Kuang XY , Yang SL , Shu BX. A study on oxidative stress in lead exposed workers . J Toxicol Environ Health 1994; 49: 256-259 .

35.

Dursun N , Dogan P , Donmez H. Plasma and erythrocyte lipid peroxide levels in workers with occupational exposure to lead . Biol Trace Elem Res 2001; 82: 29-34 .

36.

Tondon SK , Singh S , Prasad S , Srivastava S , Siddiqui MKJ. Reversal of lead induced oxidative stress by chelating agents, antioxidant or their combination in rat . Environ Res Sec A 2002; 90: 61-66 .