Abstract
Lead (Pb) is one of the most abundant heavy metals on earth considered as number one environmental persistent toxin and health hazard affecting millions of people in all age groups. After entering bloodstream, 99 % of Pb is accumulated in erythrocytes and causes poisoning. Toxic Pb effects on erythrocytes membrane’s composition of phosphatidyl serine (PS), phosphatidyl ethanolamine (PE), phosphatidyl choline (PC), and sphingomyelin (SM), and phospholipids transmethylation were determined. Lipid peroxidation in Pb-exposed erythrocytes was evaluated as malondialdehyde (MDA) formation in presence of Fe and vitamin E to understand severity of Pb toxicity and its mitigation. Pb (0.5–5.0 μM) degraded PS (12 to 31 %, P < 0.05–0.001) and elevated SM (19–51 %, P < 0.05–0.001). Composition of PC and PE were diminished (22 %) and elevated (29 %), respectively, with higher Pb exposure (5.0 μM, P < 0.001). Pb toxicity suppressed (P < 0.001) transmethylation of phospholipids in membranes (34, 41, and 50 %, respectively, with 0.5, 2.5, and 5.0 μM). Pb-induced dose-related MDA production (P < 0.05–0.001) in erythrocytes was obtained, which was accentuated in presence of Fe (P < 0.05–0.001). The vitamin E mitigated (P < 0.05–0.01) the severity of Pb-induced lipid peroxidation. The ratio PS/SM showed maximum change of −27 (P < 0.01), −30 (P < 0.01), and −54 % (P < 0.001), respectively at 0.5, 2.5, and 5.0 μM Pb exposures. Ratios PC/SM and PS/PE were at the second, whereas PE/PS at the third order. The study suggests that the mechanisms underlying distortion of compositional phospholipids, inhibition of transmethylation, and exasperated phospholipid peroxidative damage are the active phenomena of Pb toxicity in erythrocytes.
Similar content being viewed by others
References
World Health Organization (2003) Lead: assessing the environmental burden of disease at national and local levels. WHO, Geneva
DeSilva PE (1981) Determination of lead in plasma and studies on its relationship to lead in erythrocytes. Brit J Ind Med 38:209–217
Suwalsky M, Villena F, Norris B, Cuevas YF, Sotomayor CP, Zatta P (2003) Effect of lead on the human erythrocyte membrane and molecular models. J Inorg Biochem 97:308–313
Donaldson WE, Knowlers SO (1993) Is lead toxicosis a reflection of altered fatty acid composition of membranes? Comp Biochem Physiol 104C:377–379
Sakai T (2000) Biomarkers of lead exposure. Ind Health 38:127–142
Hajem S, Moreau T, Hannaert P, Lellouch J, Huel G, Hellier G, Orssaud G, Claude JR, Juguet B, Festy B, Garay RP (1990) Influence of lead on membrane ion transport in a French urban male population. Environ Res 53(2):105–108
Casper ML, Siegel GJ (1980) Inhibition by lead of human erythrocyte (Na++K+)-adenosine triphosphatase associated with binding of 210Pb to membrane fragments. Biochim Biophys Acta 600:27–35
Shafiq-ur-Rehman (1984) Effect of zinc, copper and lead toxicity of the δ-aminolevulinic acid dehydratase activity. Bull Environ Contam Toxicol 33:92–98
Abdel-Mageid AD, El-Shawarby R (2006) Alteration in erythrocyte fatty acids composition, cholesterol and phospholipids of chronic lead intoxicated male rabbits and their modulation with vitamin E. J Egypt Soc Toxicol 34:71–75
Zimmermann L, Pages N, Antebi H, Hafi A, Boudene C, Alcindor LG (1993) Lead effect on the oxidation resistance of erythrocyte membrane in rat triton-induced hyperlipidemia. Biol Trace Elem Res 38:311–318
Shafiq-ur-Rehman (1984) Lead-induced regional lipid peroxidation in brain. Toxicol Lett 21:333–338
Kuypers FA (2007) Membrane lipid alterations in hemoglobinopathies. Hematol Am Soc Hematol Educ Program 2007:68–73
Przestalski S, Sarapuk J, Kleszczyńska H, Gabrielska J, Hladyszowski J, Trela Z, Kuczera J (2000) Influence of amphililic compounds on membranes. Acta Biochim Pol 47(3):627–638
Hirata F, Axelrod J (1978) Enzymatic synthesis and rapid translocation of phosphatidylcholine by two methyltransferases in erythrocyte membranes. Proc Natl Acad Sci USA 75:2348–2352
Crews FT, Hirata F, Axelrod J (1980) Identification and properties of methyltransferases that synthesize phosphatidylcholine in rat brain synaptosomes. J Neurochem 34:1491–1498
Crew FT, Morita F, Hirata F, Axelrod J, Siraganian RP (1980) Phospholipid methylation effects immunoglobulin E-mediated histamine and arachidonic acid release in rat leukaemia basophils. Biochem Biophys Res Commun 93:42–49
Hirata F, Axelrod J (1980) Phospholipid methylation and biological signal transmission. Science 209:1082–1090
LeFur G, Phan T, Canton T, Tur C, Uzan A (1981) Evidence for a coupling between dopaminergic receptors and phospholipid methylation in mouse B lymphocytes. Life Sci 29:2737–2749
Hitzemann R, Mark C, Hirschowitz J, Garver D (1985) Characteristics of phospholipid methylation in human erythrocyte ghosts: relationship(s) to the psychoses and affective disorders. Biol Psychiatr 20:397–407
Shafiq-ur-Rehman (2003) Lead-exposed increase in movement behavior and brain lipid peroxidation in fish. J Environ Sci Health A38:631–643
Shafiq-ur-Rehman, Rehman S, Chandra O, Abdulla M (1995) Evaluation of malondialdehyde as an index of lead damage in rat brain homogenates. BioMetals 8:275–279
Naziroğlu M (2007) New molecular mechanisms on the activation of TRPM2 channels by oxidative stress and ADP-ribose. Neurochem Res 32:1990–2001
Nazıroğlu M (2012) Molecular role of catalase on oxidative stress-induced Ca(2+) signalling and TRP cation channel activation in nervous system. J Recept Signal Transduct Res 32(3):134–141
Nazıroğlu M, Simşek M, Kutlu M (2004) Moderate exercise with a dietary vitamin C and E combination protects against streptozotocin-induced oxidative damage to the blood and improves fetal outcomes in pregnant rats. Clin Chem Lab Med 42(5):511–517
Nazıroğlu M, Akkuş S, Celik H (2011) Levels of lipid peroxidation and antioxidant vitamins in plasma and erythrocytes of patients with ankylosing spondylitis. Clin Biochem 44:1412–1415
Shafiq-ur-Rehman (1991) A rapid isocratic method for the separation and quantification of major phospholipid classes by high-performance liquid chromatography. J Chromatogr 567:29–37
Fiorini RM, Curatola G, Valentino M, Governa M (1982) Effect of lead on physical state of erythrocytes and model membranes. Boll Soc Ital Biol Sper 58:871–875
Shin JH, Lim KM, Noh JY, Bae ON, Chung SM, Lee MY, Chung JH (2007) Lead-induced procoagulant activation of erythrocytes through phosphatidyleserine exposure may lead to thrombotic diseases. Chem Res Toxicol 20:38–43
Steck TL, Kant JA (1974) Preparation of impermeable ghosts and inside-out vesicles from human erythrocyte membranes. In: Fleischer L, Packer L (eds) Methods in enzymolology. Academic, Orlando, pp 172–180
Utely HC, Bernheim F, Hochstein P (1967) Effect of sulfhydryl reagents on peroxidation in microsomes. Arch Biochem Biophys 118:29–32
Hargreaves KM, Clandinin MT (1987) Phosphatidylethanolamineethyltransferase: evidence for influence of diet fat on selectivity of substrate for methylation in rat brain synaptic plasma membranes. Biochim Biophys Acta 918:97–105
Hirata F, Strittmatter WJ, Axelrod J (1979) β-adrenergic receptor agonists increase phospholipid methylation, membrane fluidity, and β-adrenergic receptor-adenylatecyclase coupling. Proc Natl Acad Sci USA 76:368–372
Tsao DA, Yu HS, Cheng JT, Ho CK, Chang HR (2000) Alterations in beta-adrenergic receptor density and adenylatecyclase activity in rat brain treated with lead. Toxicology 146:93–99
Shafiq-ur-Rehman (1991) Effect of lead on the behavioural complex stereotypes and regional brain dopamine levels in rats. Arch Environ Contam Toxicol 20:527–530
Shafiq-ur-Rehman, Mahdi AA, Hasan M (2003) Trace metal-induced lipid peroxidation in biological system. Soc Free Rad Res India Bull 2(2):12–18
Kolanjiappan K, Manoharan S, Kayalvizhi M (2002) Measurement of erythrocyte lipids, lipid peroxidation, antioxidants and osmatic fragility in cervical cancer patients. Clin Chim Acta 326:143–149
Acknowledgements
The author is highly grateful to Professor Dr. M. Ackenheil for continuous encouragement and help. This study is dedicated to his affectionate memory. Thanks are also due to Ms. Shaheen Rehman for help in analysis and preparation of the manuscript. The work was performed at the Department of Neurochemistry, Institute of Psychiatry, Ludwig Maxmilian University of Munich, Germany.
Conflict of Interest
The author reports no conflict of interest.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Shafiq-ur-Rehman Effect of Lead on Lipid Peroxidation, Phospholipids Composition, and Methylation in Erythrocyte of Human. Biol Trace Elem Res 154, 433–439 (2013). https://doi.org/10.1007/s12011-013-9745-1
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12011-013-9745-1