REVIEW PAPER
Molecular basis of lead toxicity
1
Department of Internal Medicine, Occupational Diseases and Hypertension, Wroclaw Medical University, Borowska 213, PL 50-556 Wroclaw, Poland
Head: prof. dr hab. n. med. Grzegorz Mazur
2
Department of Hygiene, Wroclaw Medical University, Mikulicza-Radeckiego 7, PL 50-368 Wroclaw, Poland
Head: prof. dr hab. n. med. Krystyna Pawlas
Med Srod. 2018;21(4):44-62
KEYWORDS
ABSTRACT
Lead represents a metal widespread in the environment, mainly due to its broad application in several branches of industry. It represents an extremely toxic an extremely toxic agent for living organisms, affecting several systems and organs, including central nervous system, hemopoetic system, circulatory and immune systems, liver and kidneys. The studies conducted in the last years enabled o evaluate numerous metabolic pathways responsible for lead toxicity. In the present study the actual data on the basic molecular pathology of lead compounds toxicity were presented: generation of oxidative stress and lesions in genetic material, modifications of neurotransmitters pathways in brain, abnormalities in immune system functioning and changes in metabolism of red cells. Summing up the above we should note that differentiation of molecular mechanisms in lead toxicity, resulting in multiple biological effects of the exposure, causes that the exposure continues to pose a significant challenge for environmental medicine and occupational medicine.
ACKNOWLEDGEMENTS
The study was funded by local grant from the Wroclaw
Medical University. The authors report no declarations of
interest.
REFERENCES (31)
1.
Xu J, Lian L, Wu C et al., Lead induces oxidative stress, DNA damage and alteration of p53, Bax and Bcl-2 expressions in mice, Food Chemical Toxicol., 2008; 46(5): 1488- 1494.
2.
Zhang H, Liu Y, Liu R et al., Molecular mechanism of leadinduced superoxide dismutase inactivation in zebrafish livers, J Phys Chem B., 2014; 118 (51): 14820-14826.
3.
Abdallah GM, El Sayed M, Abo-Salem OM, Effect of lead toxicity on coenzyme Q levels in rat tissues, Food Chem Toxicol., 2010; 48(6): 1753-1756.
4.
Zhang H, Wei K, Zhang M et al., Assessing the mechanism of DNA damage induced by lead through direct and indirect interactions, J Photochem Photobiol B.,2014; 136: 46-53.
5.
Fracasso ME, Perbellini L, Solda S, et al., Lead induced DNA strand breaks in lymphocytes of exposed workers: role of reactive oxygen species and protein kinase C, Mutat Res., 2002; 515 (1-2): 159-169.
6.
Toscano CD, Guilarte TR, Lead neurotoxicity: from exposure to molecular effects, Brain Res Brain Res. Rev. Reviews 2005; 49 (3): 529-554.
7.
Patra RC, Swarup D, Dwivedi S.K, Antioxidant effects of alfa tocopherol, ascorbic acid and L-methionine on lead induced oxidative stress to the liver, kidney and brain in rats, Toxicology 2001; 162 (2): 81-88.
8.
Hasanein P, Kazemian-Mahtaj A, Khodadadi I, Bioactive peptide carnosin protects against lead acetate-induced hepatotoxicity by abrogation of oxidative stress in rats, Pharm Biol, 2016; 54 (8): 1458-64.
9.
El-Sokkary GH, Abdel-Rahman GH, Kamel ES, Melatonin protects against lead-induced hepatic and renal toxicity in male rats, Toxicology 2005; 213 (1-2): 25-33.
10.
Danadevi K., Rozati R., Saleha-Banu B., et al., DNA damage in workers exposed to lead using comet assay, Toxicology, 2003; 187 (2-3): 183-193.
11.
Donmez H, Dursun N, Ozkul Y, et al, Increased sister chromatid exchanges in workers exposed to occupational lead and zinc, Biol Trace Elem Res, 61 (1): 105-9.
12.
Garcia-Leston J, Mendez J, Pasaro E, et al, Genotoxic effects of lead: an updated review, Environ Int, 2010; 36 (6): 623- 636.
13.
Devi KD, Banu BS, Grover P et al, Genotoxic effect of lead nitrate on mice using SCGE (comet assay), Toxicology, 2000; 145 (2-3): 195-201.
14.
Shaik AP, Sankar S, Reddy SC, et al, Lead-induced genotoxicity in lymphocytes from peripheral blood samples of humans: in vitro studies, Drug Chem Toxicol, 2006; 29 (1): 111-124.
15.
Bonacker D, Stoiber T, Bohm KJ, et al, Genotoxicity of inorganic lead salts and disturbance of microtubule function, Environ Mol Mutagen, 2005; 45 (4): 346-353.
16.
Luo M, Xu Y, Cai R, Epigenetic histone modification regulates developmental lead exposure induced hyperactivity in rats, Toxicology Lett., 2014; 225(1): 78-85.
17.
Sui L, Zhang RH, Zhang P, et al, Lead toxicity induces autophagy to protect against cell death through mTORC1 pathway in cardiofibroblasts, Biosci Rep, 2015; 35 (2).
18.
Kost A, Kasprowska D, Łabuzek K, et al, Autophagy in brain ischemia, Postepy Hig Med Dosw, 2011; 65: 524-533.
19.
Ma T, Wu X, Cai Q, et al., Lead poisoning disturbs oligodendrocytes differentiation involved in decreased expression of NCX3 inducing intracellular calcium overload, Int J Mol Sci, 2015; 16 (8): 19096-19110.
20.
Toscano CD, Hashemzadeh-Gargari H, McGlothan J.L., et al, Developmental Pb2+ exposure alters NMDAR subtypes and reduces CREB phosphorylation in the rat brain, Brain Res Dev Brain Res, 2002; 139: 217-226.
21.
Rahman A, Brew B J, Guillemin GJ, Lead dysregulates serine/ threonine protein phosphatases in human neurons, Neurochem Res., 2011; 36(2): 195-204.
22.
Yun SW, Hoyer S, Effects of low-level lead on glycolytic enzymes and puryvate dehydrogenase of rat brain in vitro: relevance to sporadic Alzheimer's disease?,J Neural Transmi, 2000; 10793): 355-368.
23.
Feng C, Gu J, Zhou F, et al, The effect of lead exposure on expression of SIRT 1 in the rat hippocampus, Environ Toxicol Pharmacol, 2016; 44: 84-92.
24.
Schneider JS, Kidd SK, Anderson DW, Influence of developmental lead exposure on expression of DNA methyltransferases and methyl cytosine-binding proteins in hippocampus, Toxicology Lett, 2013; 217(1): 75-81.
25.
Eid A, Zawia N, Consequences of lead exposure and it's emerging role as an epigenetic modifier in the aging brain, Neurotoxicology, 2015.
26.
Lidsky TI, Schneider JS, Lead neurotoxiicity in children: basic mechanisms and clinical correlates, Brain, 2003; 126(Pt1): 5-19.
27.
Dietert RR, Lee JE, Hussain I,et al., Developmental immunotoxicology of lead, Toxicol Appl Pharmacol, 2004; 198(2): 86-94.
28.
Gao D, Mondal TK, Lawrence, Lead effects on development and function of bone marrow-derived dendritic cells promote Th2 immune responses, Toxicol Appl Pharmacol, 2007; 222(1): 69-79
29.
Baranowska-Bosiacka I, Dziedziejko V, Safranow L, et al, Inhibition of erythrocyte phoshoribosyltransferases (APRT and HPRT) by Pb2+: a potential mechanism of lead toxicity, Toxicology; 2009; 25991-2): 77-83.
30.
Baranowska-Bosiacka I, Hlynczak A, The effect of lead ions on the energy metabolism of human erythrocytes in vitro, Comp Biochem Physiol C Toxicol Pharmacil., 2003; 134(3): 403-416.
31.
Belloni-Olivi., Annadata M, Goldstein GW et al., Phosphorylation of membrane proteins in erythrocytes treated with lead, Biochem J, 1996; 315(Pt2): 401-406.
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