Çocuklarda Kurşun Zehirlenmesi, Oksidatif Stres ve Tiyol Bileşiklerin Antioksidan Etkisi

Yıl 2010, , 13 - 23, 01.01.2010

Emrah Çaylak

https://doi.org/10.5222/j.child.2010.013

Öz

Kurşun, endüstride yaygın olarak kullanılmasından dolayı büyük bir çevresel sorun oluşturmaktadır. Kronik kurşun zehirlenmesi ise dünya ülkeleri ve ülkemizde çocuklar için en önemli sağlık sorunlarından biridir. Çocuklar kolayca inhibisyona ve hasara uğrayabilen hücre farklılaşması ve büyümesine sahip, gelişen bir sisteme sahiptir. Kurşun zehirlenmesine karşı daha fazla miktarda kurşun absorbe ettikleri için de yetişkinlere göre daha duyarlıdırlar. Bununla birlikte, çok düşük miktarlardaki kurşun maruziyetinin sinirsel hasar, kavrama bozukluğu, nörodavranışsal hastalıklar, hipertansiyon ve böbrek yetmezliğine yol açtığı gösterilmiştir. Kurşunun tüm mekanizması oksidatif hasarla gelişmektedir. Kurşunla uyarılan oksidatif stres başlıca eritrositlerde görülür; hem ve hemoglobin Hb sentezinin önlenmesi, eritrosit morfolojisinin ve ömrünün değiştirilmesi ana etkilerdir. Sonuçta, biriken aminolevülinik asit ALA ise, reaktif oksijen türlerinin meydana gelmesine yol açar. Buna ilaveten kurşun fonksiyonel -SH grubu taşıyan birçok enzimi inhibe ederek ve oksidatif hasara neden olarak hücrelerin pro-oksidan/antioksidan dengesinde bir bozulma da meydana getirir. Deneysel çalışmalarda tiyollerin tek başlarına veya şelatör ajanlarla birlikte kurşunun zararlı etkilerine karşı yararlı olduğu gözlenmiştir. Bu ajanlar kurşunun bazı zehirli etkilerine karşı koyar ya da kurşun maruziyeti sonrası prooksidan/antioksidan oranındaki bozulmayı dengeler. Sülfür taşıyan metiyonin, N-asetilsistein NAC , α-lipoik asit ve homosistein gibi antioksidanların endüstriyel ortamda çalışan çocuk işçilerin ya da hava kirliliğinde yaşayan çocukların kurşun zehirlenmesine karşı korunmasındaki stratejilerde kullanılması yeni bir yaklaşımdır.

Anahtar Kelimeler

Kurşun, oksidatif stres, antioksidan, α-lipoik asit, homosistein

Lead Toxication and Oxidative Stress in Children and Antioxidant Effects of Thiol Compounds

Öz

Lead causes a great environmental problem because it’s being widely used in the industry. Chronic lead intoxication is the most important health threat to children in the World and our country. Children have a developing system of cell differentiation and growth that’s more vulnerable to inhibition and damage. They’re far more susceptible to lead neurotoxicity than adults because they absorb a higher fraction of lead and. However, it has indicated that low-level exposures of lead result in neurological damage, cognitive dysfunction, neurobehavioral disorders, hypertension, and renal impairment. The mechanism all of lead has in common involves oxidative damage. Oxidative stress induced by lead is seen mainly in erythrocytes including inhibition of heme and hemoglobin Hb synthesis, and changing the erythrocytes morphology and survival. The accumulated aminolevulinic acid ALA induces ROS generation and lead also inhibits several enzymes having functional -SH groups and might cause impairment in prooxidant/antioxidant balance of cells, resulting in oxidative damage. Thiols either individually or in a combined therapy, with chelating agents have been observed to have beneficial effects against lead’s detrimental properties in experimental studies. These agents were found to be capable of abating some toxic effects of lead, or they are effective in rebalancing the impaired pro-oxidant/antioxidant ratio following lead exposure. It has been indicated that sulfur containing antioxidants, such as methionine, N-acetylcystein NAC , α-lipoic acid or homocysteine, have a novel approach to strategies for preventing for lead poisoning in industrial child workers or children living in airpollutions.

Anahtar Kelimeler

Lead, oxidative stress, antioxidant, α-lipoic acid, homocysteine

Kaynakça

• 1. Nriagu JO, Pacyna JM: Quantitative assessment of worldwide contamination of air, water and soils by trace metals. Nature 1988; 333(6169):134-9.
• 2. Kaya S, Pirinççi İ, Bilgili A, editörler. Toxicology in Veterinary Medicine [Veteriner Hekimliğinde Toksikoloji]. Metaller ve diğer inorganik ve radyoetkin maddeler. I. Baskı. Ankara: Medisan Yayınevi; 1998: 134-8.
• 3. WHO. Environmental Health Criteria 165-Inorganic lead, Geneva: 1995.
• 4. Walter SD, Yankel AJ, von Lindern IH. Age-specific risk factors for lead absorption in children. Arch Environ Health 1980; 35(1):53-8.
• 5. WHO. Major poisoning episodes from environmental chemicals, s.3-15, Geneva: 1992: 3-15.
• 6. Grandjean P. Health significance of metals- lead. In: Wallace RB, Kohatsu H, eds. Maxcy-Rosenau-Last Public Health and Preventive Medicine. 15th ed. New York: McGraw-Hill Medical, 2008: 609-11.
• 7. Karakaya A, Ilko M, Ulusu T, Akal N, Karakaya AE. Decidious teeth of children from Urban and Suburban regions in Ankara (Turkey). Bull Environ Contam Toxicol 1996; 56(1):16-20.
• 8. Sevinç E, Kösecik M, Koçyiğit A, et al. The blood lead level and the effect of lead on hematological parameters in auto industry apprentices in Sanliurfa [Şanlıurfa ilinde oto tamir atölyelerinde çalışan çıraklarda saç ve kan kurşun düzeyleri ve hematolojik değerler üzerine etkileri. Harran Tıp Fak Der 2004; 1(4):33-8.
• 9. Yapici G, Can G, Kiziler AR, Aydemir B, Timur IH. Childhood lead and cadmium exposure in a coal mening area in Yatagan, Turkey. CEHCA. 2005; 1(2):216.
• 10. Yilmaz B, Aydin M, Kaya H, et al. Environmental lead contaminatıon and blood lead levels in children and adults in Keban district. CEHCA. 2005; 1(2):217.
• 11. Gurer H, Ercal N. Can antioxidants be beneficial in the treatment of lead poisoning? Free Radic Biol Med 2000; 29(10):927-45.
• 12. Yiin SJ, Lin TH. Lead-catalyzed peroxidation of essential unsaturated fatty acid. Biol Trace Elem Res 1995; 50(2):167- 72.
• 13. El-Sokkary GH, Kamel ES, Reiter RJ. Prophylactic effect of melatonin in reducing lead-induced neurotoxicity in the rat. Cell Mol Biol Lett 2003; 8(2):461-70.
• 14. Sandhir R, Gill KD. Effect of lead on lipid peroxidation in liver of rats. Biol Trace Elem Res 1995; 48(1):91-7.
• 15. Caylak E, Aytekin M, Halifeoglu I. Antioxidant effects of methionine, alpha-lipoic acid, N-acetylcysteine and homocysteine on lead-induced oxidative stress to erythrocytes in rats. Exp Toxicol Pathol 2008; 60(4-5):289-94.
• 16. Ercal N, Gurer-Orhan H, Aykin-Burns N. Toxic metals and oxidative stress part I: mechanisms involved in metal-induced oxidative damage. Curr Top Med Chem 2001; 1(6):529-39.
• 17. Levander OA, Morris VC, Ferretti RJ. Filterability of erythrocytes from vitamin E-deficient lead-poisoned rats. J Nutr. 1977; 107(3):363-72.
• 18. Othman AI, El Missiry MA. Role of selenium against lead toxicity in male rats. J Biochem Mol Toxicol 1998; 12(6):345-9.
• 19. Gurer H, Ozgunes H, Neal R, Spitz DR, Ercal N. Antioxidant effects of N-acetylcysteine and succimer in red blood cells from lead-exposed rats. Toxicology 1998; 128(3):181-9.
• 20. El-Missiry MA. Prophylactic effect of melatonin on leadinduced inhibition of heme biosynthesis and deterioration of antioxidant systems in male rats. J Biochem Mol Toxicol 2000; 14(1):57-62.
• 21. Knowles SO, Donaldson WE. Dietary modification of lead toxicity: effects on fatty acid and eicosanoid metabolism in chicks. Comp Biochem Physiol C 1990; 95(1):99-104.
• 22. Lawton LJ, Donaldson WE. Lead-induced tissue fatty acid alterations and lipid peroxidation. Biol Trace Elem Res 1991; 28(2):83-97.
• 23. Ribarov SR, Benov LC. Relationship between the hemolytic action of heavy metals and lipid peroxidation. Biochim Biophys Acta 1981; 640(3):721-6.
• 24. Kumar KS, Rowse C, Hochstein P. Copper-induced generation of superoxide in human red cell membrane. Biochem Biophys Res Commun. 1978; 83(2):587-92.
• 25. Costa CA, Trivelato GC, Pinto AM, Bechara EJ. Correlation between plasma 5-aminolevulinic acid concentrations and indicators of oxidative stress in lead-exposed workers. Clin Chem 1997; 43(7):1196-202.
• 26. Kalia K, Flora SJ. Strategies for safe and effective therapeutic measures for chronic arsenic and lead poisoning. J Occup Health 2005; 47(1):1-21.
• 27. Solliway BM, Schaffer A, Pratt H, Yannai S. Effects of exposure to lead on selected biochemical and haematological variables. Pharmacol Toxicol 1996; 78(1):18-22.
• 28. Warren MJ, Cooper JB, Wood SP, Shoolingin-Jordan PM. Lead poisoning, haem synthesis and 5-aminolaevulinic acid dehydratase. Trends Biochem Sci 1998; 23(6):217-21.
• 29. Murray RK. Porphyrins and Bile Pigments. In: Murray RK, Granner DK, Mayes PA, Rodwell VW, eds. Harper’s Biochemistry. 25th ed. Stamford: Appleton & Lange; 2000; p. 359-73.
• 30. James MF, Hift RJ. Porphyrias. Br J Anaesth. 2000; 85(1):143-53.
• 31. Fujita H, Nishitani C, Ogawa K. Lead, chemical porphyria, and heme as a biological mediator. Tohoku J Exp Med 2002; 196(2):53-64.
• 32. Ercal N, Treeratphan P, Lutz P, Hammond TC, Matthews RH. N-acetylcysteine protects Chinese hamster ovary (CHO) cells from lead-induced oxidative stress. Toxicology 1996; 108(1-2):57-64.
• 33. Hermes-Lima M, Valle VG, Vercesi AE, Bechara EJ. Damage to rat liver mitochondria promoted by deltaaminolevulinic acid-generated reactive oxygen species: connections with acute intermittent porphyria and lead-poisoning. Biochim Biophys Acta 1991; 1056(1):57-63.
• 34. Atmaca G. Antioxidant effects of sulfur-containing amino acids. Yonsei Med J 2004; 45(5):776-88.
• 35. Parcell S. Sulfur in human nutrition and applications in medicine. Altern Med Rev 2002; 7(1):22-44.
• 36. Fang YZ, Yang S, Wu G. Free radicals, antioxidants, and nutrition. Nutrition 2002; 18(10):872-9.
• 37. Yardim-Akaydin S, Ozkan Y, Ozkan E, Torun M, Simsek B. The role of plasma thiol compounds and antioxidant vitamins in patients with cardiovascular diseases. Clin Chim Acta. 2003; 338(1-2):99-105.
• 38. Finkelstein JD, Martin JJ, Harris BJ. Methionine metabolism in mammals. The methionine-sparing effect of cystine. J Biol Chem 1998; 263(24):11750-4.
• 39. Verhoef P, Stampfer MJ, Buring JE, et al. Homocysteine metabolism and risk of myocardial infarction: relation with vitamins B6, B12, and folate. Am J Epidemiol 1996; 143(9):845-59.
• 40. Tandon SK, Flora SJ, Singh S. Influence of pyridoxine (vitamin B6) on lead intoxication in rats. Ind Health 1987; 25(2):93-6.
• 41. McGowan C. Influence of vitamin B6 status on aspects of lead poisoning in rats. Toxicol Lett 1989; 47(1):87-93.
• 42. Stadtman ER, Van Remmen H, Richardson A, Wehr NB, Levine RL. Methionine oxidation and aging. Biochim Biophys Acta 2005; 1703(2):135-40.
• 43. Patra RC, Swarup D, Dwivedi SK. Antioxidant effects of alpha tocopherol, ascorbic acid and L-methionine on lead induced oxidative stress to the liver, kidney and brain in rats. Toxicology 2001; 162(2):81-8.
• 44. Çaylak E, Halifeoğlu İ. Effects of sulfur-containing antioxidants on malondialdehyde and catalase levels of liver, kidney and brain in lead-exposed rats [Sülfür içeren antioksidanların kurşuna maruz kalmış ratlarda karaciğer, böbrek ve beyin MDA ve katalaz düzeylerine antioksidan etkileri]. Türkiye Klinikleri J Med Sci 2007; 27(1):1-8.
• 45. Caylak E, Halifeoglu I, Aydin S, Telo S, Bulmus O, Celik H. The effects of sulfur-containing compounds on total antioxidant capacity levels of liver, kidney and brain in leadexposed rats. Türkiye Klinikleri J Med Sci 2007; 27(6):823-8.
• 46. Flora GJ, Seth PK. Beneficial effects of S-adenosyl-Lmethionine on aminolevulinic acid dehydratase, glutathione, and lipid peroxidation during acute lead-ethanol administration in mice. Alcohol 1999; 18(2-3):103-8.
• 47. Ercal N, Treeratphan P, Lutz P, Hammond TC, Matthews RH. N-actylcysteine protects Chinese hamster ovary (CHO) cells from lead-induced oxidative stress. Toxicology. 1996; 108(1-2):57-64.
• 48. Ercal N, Treeratphan P, Hammond TC, Matthews RH, Grannemann NH, Spitz DR. In vivo indices of oxidative stress in lead-exposed C57BL/6 mice are reduced by treatment with meso-2,3-dimercaptosuccinic acid or N-acetylcysteine. Free Radic Biol Med 1996; 21(2):157-61.
• 49. Neal R, Yang P, Fiechtl J, Yildiz D, Gurer H, Ercal N. Prooxidant effects of delta-aminolevulinic acid (delta-ALA) on Chinese hamster ovary (CHO) cells. Toxicol Lett 1997; 91(3):169-78.
• 50. Packer L, Witt EH, Tritschler HJ. Alpha-Lipoic acid as a biological antioxidant. Free Radic Biol Med 1995; 19(2):227- 50.
• 51. Sivaprasad R, Nagaraj M, Varalakshmi P. Combined efficacies of lipoic acid and 2,3-dimercaptosuccinic acid against lead-induced lipid peroxidation in rat liver. J Nutr Biochem 2004; 15(1):18-23.
• 52. Moini H, Packer L, Saris NE. Antioxidant and prooxidant activities of alpha-lipoic acid and dihydrolipoic acid. Toxicol Appl Pharmacol 2002; 182(1):84-90.
• 53. Gurer H, Ozgunes H, Oztezcan S, Ercal N. Antioxidant role of alpha-lipoic acid in lead toxicity. Free Radic Biol Med 1999; 27(1-2):75-81.
• 54. Gurer H, Neal R, Yang P, Oztezcan S, Ercal N. Captopril as an antioxidant in lead-exposed Fischer 344 rats. Hum Exp Toxicol 1999; 18(1):27-32.
• 55. Ding Y, Gonick HC, Vaziri ND. Lead promotes hydroxyl radical generation and lipid peroxidation in cultured aortic endothelial cells. Am J Hypertens 2000; 13(5 Pt 1):552-5.
• 56. Gurer H, Ozgunes H, Saygin E, Ercal N. Antioxidant effect of taurine against lead-induced oxidative stress. Arch Environ Contam Toxicol. 2001; 41(4):397-402.
• 57. Finkelstein JD, Martin JJ. Homocysteine. Int J Biochem Cell Biol 2000; 32(4):385-9.
• 58. Zappacosta B, Mordente A, Persichilli S, Giardina B, De Sole P. Effect of homocysteine on polymorphonuclear leukocyte activity and luminol-dependent chemiluminescence. Luminescence. 2000; 15(4):257-60.
• 59. Zappacosta B, Mordente A, Persichilli S, et al. Is homocy- steine a pro-oxidant? Free Radic Res 2001; 35(5):499-505.
• 60. Kang AH, Trelstad RL. A collagen defect in homocystinuria. J Clin Invest 1973; 52(10):2571-8.
• 61. Zhou J, Moller J, Danielsen CC, et al. Dietary supplementation with methionine and homocysteine promotes early atherosclerosis but not plaque rupture in ApoE-deficient mice. Arterioscler Thromb Vasc Biol 2001; 21(9):1470-6.