Lubyanova I. P. 1, Lugovskiy S. P. 1, Mykhaylyk O. M. 2, Dudchenko N. A.3
DISORDERS OF IRON METABOLISM IN LEAD EXPOSURE (CLINICAL AND EXPERIMENTAL STUDIES)
1State Institution "Institute for Occupational Health of the National Academy of Medical Sciences of Ukraine", Kyiv
2Ethris GmbH, Planegg, Germany
3M. P. Semenenko Institute of Geochemistry, Mineralogy and Ore Formation of the National Academy of Sciences of Ukraine, Kyiv
Full article (PDF), ENG
Actuality. A problem of the part of lead in development of body iron overload is actively discussed in the modern literature. In this, disorders of heme and nonheme iron in the body in lead intoxications is still not sufficiently investigated.
Purpose of the work. To study peculiarities of disorders of heme and nonheme iron in workers, exposed to lead in production conditions as well as to investigate morphological manifestations of hemosiderosis on an experimental model of lead intoxication in rats.
Materials and methods. 19 workers of an art glass factory, aged 42 ± 11 (main group), occupationally exposed to lead as well as 17 workers of the control group, aged 40 ± 14, were subjects on the study. Indices of iron metabolism (transferrin iron concentration [Tf-Fe], transferrin protein concentration [Tf], transferrin saturation [% Tf], ferritin iron [Ft-Fe] and chelatable iron [Df-Fe] concentration in blood, transferrin iron concentration in blood cells, transferrin and ferritin iron concentrations in plasma, iron concentration in serum) were studied, using a quantitative method of electronic spin resonance (ESR). Also, 36 Vistar male rats were used for reproducing a model of acute, subacute and chronic lead intoxication for morphological assessment of iron (III) metabolism disorders. For this purpose, histological slides were prepared from the liver pieces, filled into paraffin, with the use of microtome and Pearl’ reaction.
Results. It is seen that occupational contact with lead results in a significant increase of serum iron concentration, transferrin iron concentration in blood cells and transferrin saturation, promoting development of a body iron overload. The results of experiments is the evidence of this, where development of expressiveness of interstitial hemosiderosis of various degree has been stated.
Key words: lead poisoning, experimental lead intoxication, transferrine, ferritin, hemosiderosis, electronic spin resonance, secondary iron overload
- Silbergeld, E. K. 2003, “Facilitative mechanisms of lead as a carcinogen”, Mutat. Res., v. 533, no. 1–2, pp. 121–133. https://doi.org/10.1016/j.mrfmmm.2003.07.010
- IPCS. Environmental health criteria 165. “Inorganic lead”. [Electronic resource]. Geneva: WHO. Mode of access: http://www.inchem.org/documents /ehc/ehc/ ehc165.htm
- Caballes, F. R., Bonkovsk, H. L., Sendi, H. 2012, “He pa titis C, porphyria cutanea tarda and liver iron: an update”, Liver International., v. 32, no. 6, pp. 880–893. https://doi.org/10.1111/j.1478-3231.2012.02794.x
- Richter, G., Velasquez, M. J., Shedd, R. 1979, “Ferritin in rat kidneys with specific lesions due to a single dose of lead”, Am. J. Pathol., no. 94, pp. 483–95.
- Wright, R. O., Silverman, E. K., Schwartz, J. [et al.]. 2004, “Association between hemochromatosis genotype and lead exposure among elderly men: the normative aging study”, Environ. Health Perspect., v. 112, no. 6. pp. 746–750. https://doi.org/10.1289/ehp.6581
- Rocha, M. E., Ferreira, A. M., Bechara, E. J. 2000, “Roles of phosphate and an enoyl radical in ferritin iron mobilization by 5-aminolevulinic acid”, Free Radic. Biol. Med. no. 29. pp. 1272–1279. https://doi.org/10.1016/S0891-5849(00)00437-8
- Lubyanova, I., Mykhilyk, O., Dudchenko, N., Lu govsky S. 2002, “Iron overload upon occupational lead exposure”. In: Macro and Trace Elements. (21. Workshop, October 18th- and 19th, 2002. University, Jena). Schubert-Verlag : Leipzig. pp.1059–1067.
- Minotti, G. 1992, “The role of an endogenous nonheme iron in microsomal redox reactions”, Arch. Biochem. Biophys., no. 297, pp. 189–198. https://doi.org/10.1016/0003-9861(92)90661-F
- Di Mascio, P., Teixeira, P. C., Onuki, J. [et al.]. 2000, “DNA damage by 5-aminolevulinic and 4,5-dioxovaleric acids in the presence of ferritin”, Arch. Biochem. Biophys., no. 373, pp. 368–374. https://doi.org/10.1006/abbi.1999.1551
- Demassi, M., Penatti, C. A., DeLucia, R. 1996, “The prooxidant effect of 5-aminolevulinic acid in the brain tissue of rats: implications in neuropsychiatric manifestations in porphyrias”, Free Rad. Biol. Med., no. 20, pp. 291–299. https://doi.org/10.1016/0891-5849(95)02035-7
- Klausner R., D., Rouault T. A., Harford J. B. 1993, “Regulating the fate of mRNA: the control of cellular iron metabolism”, Cell, no. 72, pp. 19–28. https://doi.org/10.1016/0092-8674(93)90046-S
- Mykhaylyk, O., Dudchenko, N. 1998, “Nonheme iron determination in biological samples on evidence derived from electron spin resonance data”, Metal Irons in Biology and Medicine (Eds. Collery Ph., Brätter P., Negretti de Brätter V. [et al.]), v. 5: John Libbey Eurotext, Paris, pp. 3–7.
- Dudchenko, N., Mykhaylyk, O. 1999. “Quant ification of chelatable iron in biological tissues using ESR tecknique on complexation with desferrioxamine B”, Biochemistry, v. 71, no. 3, pp. 122–127 (in Ukrainian).
- Mykhaylyk, O., Dudchenko, N., Pyasetskaya, N. [et al.]. 2000, “Nonheme iron exchange indices in the whole blood of healthy adults and neonates”, Mengen- und Spurenelemente (20 Arbeitstagung, 2 und 3 Dezember 2000. Friedrich-Schiller-Unuversitat, Jena). Schubert-Verlag : Leipzig, pp. 489–496.
- Arkhipova, O. G., Shatskaya, N. N., Semenova, L. S. [et al.]. 1988, “Novel biochemical methods of investigation in profpathology”, Moskow : Meditsina, 208 p. (in Russian).
- Barbosa, Jr. F., Tanus-Santos, J. E., Gerlach, R. F., Parsons P. J. 2005, “A critical review of biomarkers used for monitoring human exposure to lead: advantages, limitations, and future needs”, Environ. Health Perspect., v. 113, no. 12, pp. 1669–1674. https://doi.org/10.1289/ehp.7917
- Flora, G., Gupta, D., Tiwari, A. 2012, “Toxicity of lead: A review with recent updates”, Interdisci., v. 5, no. 2, pp. 47–58. https://doi.org/10.2478/v10102-012-0009-2
- Kasperczyk, A., Prokopowicz, A., Dobrakowski, M. [et al.]. 2012, “The effect of occupational lead exposure on blood levels of zinc, iron, copper, selenium and related proteins”, Biol. Trace Elem. Res., v. 150, pp. 49–55. https://doi.org/10.1007/s12011-012-9490-x
- Halliwell, B. 1992, “Iron and damage to biomolecules”, Iron and Human Disease. (Ed. Randall B. Lauffer ), CRC Press, Boca Raton,. pp. 209–236. https://doi.org/10.1201/9781351073899-8
- Cooper, C., Brown, G. 1995, “The interactions between nitric oxide and brain nerve terminals as studied by electron paramagnetic resonance”, Biochem. Biophys. Res. Commun., no. 1212, pp. 404-412. https://doi.org/10.1006/bbrc.1995.1984
- Richardson, D., Milnes, K. 1997, “The potential of iron chelators of the pyridoxal isonicotinoyl hydrazone class as effective antiproliferative agents II: the mechanism of action of ligands derived from salicylaldehyde benzoyl hydrazone and 2-hydroxy-1-naphthylaldehyde benzoyl hydrazone”, Blood, no. 89, pp. 3025-3038. https://doi.org/10.1182/blood.V89.8.3025
- Verheij, J., Voortman, J., Van Nieuwkerk, C. M. [et al.]. 2009, “Hepatic morphopathologic findings of lead poisoning in a drug addict: a case report”, J. Gastrointestin. Liver Dis., v. 18, no. 2, pp. 225-227.
- Lugovskoy, S. P. 2009. “Morphofunctional characteristic of hemosiderosis at experimental lead intoxication”, Actual Probl. Transport. Medic., no. 2, pp. 124132 (in Ukrainian).
- Sano, S., Inoue, S., Tanabe, Y. [et al.]. 1959, “Significance of mitochondria for porphyrin and heme biosynthesis”, Science, no. 129, pp. 275-276. https://doi.org/10.1126/science.129.3344.275
- Lubyanova, I., Voitovich, I., Primin, M. 2014. “Magnetometric noncontact method for determination of iron accumulation in rat liver with lead intoxication”. The 15-th International Symposium on Trace Elements in Man and Animals, Orlando, Florida. USA. pp. 73.