Skip to main content
SpringerLink
Log in

Mechanisms of Lead Toxicity and Their Pathogenetic Correction

  • Reviews
  • Published:
Journal of Evolutionary Biochemistry and Physiology Aims and scope Submit manuscript

Abstract

The review addresses the mechanisms of lead acetate toxic effects on the cardiovascular and nervous systems, as well as visceral organs. Experimental and clinical studies conducted in recent years have shown an important pathogenetic role of oxidative stress in the dysfunction of the vascular endothelium, leading to the development of pathology of internal organs, especially the kidneys and liver. Activation of free-radical processes and disruption of cellular bioenergetics are accompanied by a decrease in the production of nitric oxide, a major vasodilator, leading to endothelial dysfunction, increased vascular tone, and eventually to systemic vasoconstriction. On the other hand, reactive oxygen species and lipid peroxidation products stimulate the synthesis of pro-inflammatory cytokines and pro-apoptotic proteins, causing intracellular inflammatory processes in the visceral organs, DNA damage, cell apoptosis, as well as persistent renal and hepatic dysfunction. In this regard, there have been developed various pharmaceuticals with antioxidant and anti-inflammatory properties, and those able to improve cellular bioenergetics of the visceral organs. Among them are such phyto-derivatives as Moringa oleifera extract, curcumin, vitamin C, vitamin C–curcumin combination, as well as analogs of endogenous antioxidants, L-carnitine and coenzyme Q10. All tissues contain significant amounts of ubiquinone, which is essential for cellular functions, including electron and proton transport in the mitochondrial respiratory chain and antioxidant defense.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1.

Similar content being viewed by others

REFERENCES

  1. de Souza ID, de Andrade AS, Dalmolin RJS (2018) Lead-interacting proteins and their implication in lead poisoning. Crit Rev Toxicol 48(5):375–386. https://doi.org/10.1080/10408444.2018.1429387

    Article  CAS  PubMed  Google Scholar 

  2. Ericson B, Gabelaia L, Keith J, Kashibadze T, Beraia N, Sturua L, Kazzi Z (2020) Elevated Levels of Lead (Pb) Identified in Georgian Spices. Ann Glob Health 86(1):124. https://doi.org/10.5334/aogh.3044

    Article  PubMed  PubMed Central  Google Scholar 

  3. Mani MS, Kabekkodu SP, Joshi MB, Dsouza HS (2019) Ecogenetics of lead toxicity and its influence on risk assessment. Hum Exp Toxicol 38(9):1031–1059. https://doi.org/10.1177/0960327119851253

    Article  CAS  PubMed  Google Scholar 

  4. Obeng-Gyasi E (2019) Sources of lead exposure in various countries. Rev Environ Health 34(1):25–34. https://doi.org/10.1515/reveh-2018-0037

    Article  CAS  PubMed  Google Scholar 

  5. Boskabady M, Marefati N, Farkhondeh T, Farzaneh Sh, Farshbaf A, Boskabady MH (2018) The effect of environmental lead exposure on human health and the contribution of inflammatory mechanisms, a review. Environment Int 120:404–420. https://doi.org/10.1016/j.envint.2018.08.013

    Article  CAS  Google Scholar 

  6. Caito S, Lopes ACBA, Paoliello MB, Aschner M (2017) Toxicology of Lead and Its Damage to Mammalian Organs. In: Sigel A, Sigel H, Sigel RKO (eds) Lead: Its Effects on Environment and Health. De Gruyter, Berlin, pp 501–534. https://doi.org/10.1515/9783110434330-016

    Chapter  Google Scholar 

  7. Minigalieva IA, Shtin TN, Makeyev OH, Panov VG, Privalova LI, Gurvic VB, Sutunkova MP, Bushueva TV, Sakhautdinova RR, Klinova SV, Solovyeva SN, Chernyshov IN, Shuman EA, Korotkov AA, Katsnelson BA (2020) Some outcomes and a hypothetical mechanism of combined lead and benzo(a)pyrene intoxication, and its alleviation with a complex of bioprotectors. Toxicol Rep 12(7):986–994. https://doi.org/10.1016/j.toxrep.2020.08.004

    Article  CAS  Google Scholar 

  8. Mani MS, Joshi MB, Shetty RR, DSouza VL, Swathi M, Kabekkodu SP, Dsouza HS (2020) Lead exposure induces metabolic reprogramming in rat models. Toxicol Lett 15;335:11–27. https://doi.org/10.1016/j.toxlet.2020.09.010

    Article  CAS  Google Scholar 

  9. Kuz’mina LP, Hotuleva A, Bezrukavnikova LM, Sorkina NS, Cidil’kovskaya YeS (2018) The use of modern clinical and laboratory methods of research in the conduct of biological monitoring of the impact of lead on the body of workers at a lead processing enterprise. Public Health and Habitat 7:(304). https://cyberleninka.ru/article/n/ispolzovanie-sovremennyh-kliniko-laboratornyh-metodov-issledovaniya-pri-provedenii-biologicheskogo-monitoringa-vozdeystviya-svintsa

    Google Scholar 

  10. Rahman Z, Singh VP (2019) The relative impact of toxic heavy metals (THMs) (arsenic (As), cadmium (Cd), chromium (Cr)(VI), mercury (Hg), and lead (Pb)) on the total environment: an overview. Environ Monit Assess 191(7):419. https://doi.org/10.1007/s10661-019-7528-7

    Article  CAS  PubMed  Google Scholar 

  11. Al Osman M, Yang F, Massey IY (2019) Exposure routes and health effects of heavy metals on children. Biometals 32(4):563–573. https://doi.org/10.1007/s10534-019-00193-5

    Article  CAS  PubMed  Google Scholar 

  12. Evens A, Hryhorczuk D, Lanphear BP, Rankin К, Lewis DA, Forst L, Rosenberg D (2015) The impact of low-level lead toxicity on school performance among children in the Chicago Public Schools: a population-based retrospective cohort study. Environ Health 14: 21. https://doi.org/10.1186/s12940-015-0008-9

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Fan Y, Zhao X, Yu J, Xie J, Li C, Liu D, Tang C, Wang C (2020) Lead-induced oxidative damage in rats/mice: A meta-analysis. J Trace Elem Med Biol 58:126443. https://doi.org/10.1016/j.jtemb.2019.126443

    Article  CAS  PubMed  Google Scholar 

  14. Bakulski KM, Seo YA, Hickman RC, Brandt D, Vadari HS, Hu H, Park SK (2020) Heavy Metals Exposure and Alzheimer’s Disease and Related Dementias. J Alzheimers Dis 76(4):1215–1242. https://doi.org/10.3233/JAD-200282

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Abdel-Daim MM, Alkahtani S, Almeer R, Albasher G (2020) Alleviation of lead acetate-induced nephrotoxicity by Moringa oleifera extract in rats: highlighting the antioxidant, anti-inflammatory, and anti-apoptotic activities. Environ Sci Pollut Res Int 27(27):33723–33731. https://doi.org/10.1007/s11356-020-09643-x

    Article  CAS  PubMed  Google Scholar 

  16. Alhusaini AM, Faddah LM, Hasan IH, Jarallah SJ, Alghamdi SH, Alhadab NM, Badr A, Elorabi N, Zakaria E, Al-Anazi A (2019) Vitamin C and Turmeric Attenuate Bax and Bcl-2 Proteins’ Expressions and DNA Damage in Lead Acetate-Induced Liver Injury. Dose Response 17(4):1559325819885782. https://doi.org/10.1177/1559325819885782

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Li Y, Lv H, Xue C, Dong N, Bi C, Shan A (2021) Plant Polyphenols: Potential Antidotes for Lead Exposure. Biol Trace Elem Res 199(10):3960–3976. https://doi.org/10.1007/s12011-020-02498-w

    Article  CAS  PubMed  Google Scholar 

  18. Gundacker C, Forsthuber M, Szigeti T, Kakucs R, Mustieles V, Fernandez MF, Bengtsen E, Vogel U, Hougaard KS, Saber AT (2021) Lead (Pb) and neurodevelopment: A review on exposure and biomarkers of effect (BDNF, HDL) and susceptibility. Int J Hyg Environ Health 238:113855. https://doi.org/10.1016/j.ijheh.2021.113855

    Article  CAS  PubMed  Google Scholar 

  19. Metryka E, Chibowska K, Gutowska I, Falkowska A, Kupnicka P, Barczak K, Chlubek D, Baranowska-Bosiacka I (2018) Lead (Pb) Exposure Enhances Expression of Factors Associated with Inflammation. Int J Mol Sci 20;19(6):1813. https://doi.org/10.3390/ijms19061813

    Article  CAS  Google Scholar 

  20. Dzugkoev SG, Dzugkoeva FS, Margieva OI, Mozhaeva IV (2022) Analysis of the mechanisms of violation of the functional parameters of internal organs in saturnism in the experiment in rats. Bull Exp Biol Med 173(2): 177–181. https://doi.org/10.47056/0365-9615-2022-173-2-177-181

    Article  Google Scholar 

  21. Friedrich T, Tavraz NN, Junghans C (2016) ATP1A2 Mutations in Migraine: Seeing through the Facets of an Ion Pump onto the Neurobiology of Disease. Front Physiol 7:239. https://doi.org/10.3389/fphys.2016.00239

    Article  PubMed  PubMed Central  Google Scholar 

  22. Yücebilgiç G, Bilgin R, Tamer L, Tükel S (2003) Effects of lead on Na(+)–K(+)ATPase and Ca(+2)ATPase activities and lipid peroxidation in blood of workers. Int J Toxicol 22(2):95–97. https://doi.org/10.1080/10915810305096

    Article  PubMed  Google Scholar 

  23. Nazima B, Manoharan V, Miltonprabu S (2016) Oxidative stress induced by cadmium in the plasma, erythrocytes and lymphocytes of rats: Attenuation by grape seed proanthocyanidins. Hum Exp Toxicol 35(4):428–447. https://doi.org/10.1177/0960327115591376

    Article  CAS  PubMed  Google Scholar 

  24. Kloza M, Baranowska-Kuczko M, Toczek M, Kusaczuk M, Sadowska O, Kasacka I, Kozłowska H (2019) Modulation of Cardiovascular Function in Primary Hypertension in Rat by SKA-31, an Activator of K Ca 2.x and K Ca 3.1 Channels. Int J Mol Sci 20(17):4118. https://doi.org/10.3390/ijms20174118

    Article  CAS  PubMed Central  Google Scholar 

  25. Al-Megrin WA, Soliman D, Kassab RB, Metwally DM, Ahmed E Abdel Moneim, El-Khadragy MF (2020) Coenzyme Q10 Activates the Antioxidant Machinery and Inhibits the Inflammatory and Apoptotic Cascades Against Lead Acetate-Induced Renal Injury in Rats. Front Physiol 7:11:64. https://doi.org/10.3389/fphys.2020.00064

    Article  Google Scholar 

  26. Satarug S, C Gobe G, A Vesey D, Phelps KR (2020) Cadmium and Lead Exposure, Nephrotoxicity, and Mortality. Toxics 8(4):86. https://doi.org/10.3390/toxics8040086

    Article  CAS  PubMed Central  Google Scholar 

  27. Abdelhamid FM, Mahgoub HA, Ateya AI (2020) Ameliorative effect of curcumin against lead acetate-induced hemato-biochemical alterations, hepatotoxicity, and testicular oxidative damage in rats. Environ Sci Pollut Res Int 1:10950–10965. https://doi.org/10.1007/s11356-020-07718-3

    Article  CAS  Google Scholar 

  28. Okesola MA, Ajiboye BO, Oyinloye BE, Ojo OA (2019) Effect of Zingiber officinale on some biochemical parameters and cytogenic analysis in lead-induced toxicity in experimental rats. Toxicol Mech Methods 29(4):255–262. https://doi.org/10.1080/15376516.2018.1558321

    Article  CAS  PubMed  Google Scholar 

  29. Fiorim J, Simões MR, de Azevedo BF, Ribeiro RF Junior, Dos Santos L, Padilha AS, Vassallo DV (2020) Increased endothelial nitric oxide production after low level lead exposure in rats involves activation of angiotensin II receptors and PI3K/Akt pathway. Toxicology 443:152557. https://doi.org/10.1016/j.tox.2020.152557

    Article  CAS  PubMed  Google Scholar 

  30. Abdel-Zaher AO, Abd-Ellatief RB, Aboulhagag NA, Farghaly HSM, Al-Wasei FMM (2019) The interrelationship between gasotransmitters and lead-induced renal toxicity in rats. Toxicol Lett 310:39–50. https://doi.org/10.1016/j.toxlet.2019.04.012

    Article  CAS  PubMed  Google Scholar 

  31. Apyhtina EA, Kocuba AV, Korkach JuP, Andrusishina IN, Lampeka EG (2007) Vasotoxic effect of lead: the role of disturbances in the metabolism of endogenous nitric oxide. Ukr J Occupat Med 3(11):56–62. https://doi.org/10.33573/ujoh2007.03.056

    Article  Google Scholar 

  32. Yakimova NL, Sosedova LM, Vokina VA, Titov EA, Novikov MA (2017) Experimental lead intoxication symptoms with hyperglycemia state. Med Tr Prom Eko 2:54–56.

    Google Scholar 

  33. El-Sherbini ES, El-Sayed G, El Shotory R, Gheith N, Abou-Alsoud M, Harakeh SM, Karrouf GI (2017) Ameliorative effects of l-carnitine on rats raised on a diet supplemented with lead acetate. Saudi J Biol Sci 24(6):1410–1417. https://doi.org/10.1016/j.sjbs.2016.08.010

    Article  CAS  PubMed  Google Scholar 

  34. Mazandaran AA, Khodarahmi P (2021) The protective role of Coenzyme Q10 in metallothionein-3 expression in liver and kidney upon rats’ exposure to lead acetate. Mol Biol Rep 48(4):3107–3115. https://doi.org/10.1007/s11033-021-06311-2

    Article  CAS  PubMed  Google Scholar 

  35. Abdallah GM, El-Sayed el-SM, Abo-Salem OM (2010) Effect of lead toxicity on coenzyme Q levels in rat tissues. Food Chem Toxicol 48(6):1753–1756. https://doi.org/10.1016/j.fct.2010.04.006

    Article  CAS  PubMed  Google Scholar 

  36. Rocha A, Trujillo KA (2019) Neurotoxicity of low-level lead exposure: History, mechanisms of action, and behavioral effects in humans and preclinical models. Neurotoxicology 73:58–80. https://doi.org/10.1016/j.neuro.2019.02.021

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Yousef AOS, Fahad AA, Moneim AEA, Metwally DM, El-Khadragy MF, Kassab RB (2019) The Neuroprotective Role of Coenzyme Q10 Against Lead Acetate-Induced Neurotoxicity Is Mediated by Antioxidant, Anti-Inflammatory and Anti-Apoptotic Activities. Int J Environ Res Public Health 16(16):2895. https://doi.org/10.3390/ijerph16162895

    Article  CAS  Google Scholar 

  38. Hargreaves I, Heaton RA, Mantle D (2020) Disorders of Human Coenzyme Q10 Metabolism: An Overview. Int J Mol Sci 21(18):6695. https://doi.org/10.3390/ijms21186695

    Article  CAS  PubMed Central  Google Scholar 

  39. Goroshko OA, Krasnykh LM, Kukes VG, Zozina VI (2019) Significance of the redox status of coenzyme Q10 as a biomarker of oxidative stress. Bull Scientif Center for Expertise of Med Applicat 9(3):146–152. https://cyberleninka.ru/article/n/znachenie-redoks-statusa-koenzima-q10-kak-biomarkera-okislitelnogo-stressa

    CAS  Google Scholar 

  40. Pradedova EV, Nimaeva OD, Salyaev RK (2014) Redox enzymes of Red Beetroot vacuoles (Beta vulgaris L.). J Stress Physiol Biochem 4: 98–117. https://cyberleninka.ru/article/n/redox-enzymes-of-red-beetroot-vacuoles-beta-vulgaris-l

    Google Scholar 

Download references

Funding

This review was written within the state budget-funded scientific research assignment to the Institute of Biomedical Research, Branch of the Vladikavkaz Scientific Center of the Russian Academy of Sciences.

Author information

Authors and Affiliations

  1. Institute of Biomedical Research, Branch of the Vladikavkaz Scientific Center of the Russian Academy of Sciences, Vladikavkaz, Russia

    S. G. Dzugkoev, F. S. Dzugkoeva & O. I. Margieva

Authors
  1. S. G. Dzugkoev
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. F. S. Dzugkoeva
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. O. I. Margieva
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Conceptualization and editing the manuscript (S.G.D.); literature data collection, analysis of publications, writing and editing the manuscript (S.G.D., F.S.D., O.I.M.).

Corresponding author

Correspondence to S. G. Dzugkoev.

Ethics declarations

CONFLICT OF INTEREST

The authors declare that they have neither evident nor potential conflict of interest related to the publication of this review article.

Additional information

Translated by A. Polyanovsky

Russian Text © The Author(s), 2022, published in Rossiiskii Fiziologicheskii Zhurnal imeni I.M. Sechenova, 2022, Vol. 108, No. 5, pp. 626–635https://doi.org/10.31857/S0869813922050028.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Dzugkoev, S.G., Dzugkoeva, F.S. & Margieva, O.I. Mechanisms of Lead Toxicity and Their Pathogenetic Correction. J Evol Biochem Phys 58, 807–814 (2022). https://doi.org/10.1134/S0022093022030140

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1134/S0022093022030140

Keywords:

Search

Navigation