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Late-life Cardiac Injury in Rats following Early Life Exposure to Lead: Reversal Effect of Nutrient Metal Mixture

  • Chand Basha DavuljigariEmail author
  • Rajarami Reddy Gottipolu
Article
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Abstract

Early-life exposure to lead (Pb) can lead to health effects in later life. The neurotoxic effects of Pb have been well documented but its effects on the heart are poorly elucidated. We examined the late life cardiac impairments resulting from developmental exposure to Pb. Further, we investigated the protective effect of the nutrient metal mixture containing calcium (Ca), zinc (Zn) and iron (Fe) against Pb-induced long-term effects on cardiac functions.Male albino rats were lactationally exposed to 0.2% Pb-acetate or 0.2% Pb-acetate together nutrient metal mixture as 0.02% in drinking water of the mother from PND 1 to PND 21. The results showed increased levels of serum total cholesterol (TC), triglycerides (TG), low-density lipoproteins (LDLs) and lactate dehydrogenase (LDH) activity at postnatal day (PND) 28 [young], 4 months [adult] and 18 months [old] age group rats. Most notably, exposure to Pb decreased the activities of mitochondrial superoxide dismutase (SOD), thioredoxin reductase (TrxR), aconitase (Acon), isocitrate dehydrogenase (ICDH), xanthine oxidase (XO) and total antioxidant status while the MDA levels increased in all selected age groups of rats. The histological findings showed an age-dependent response to Pb exposure evidenced by extensive degeneration and necrosis in cardiac muscle, disruption in muscle connectivity, hemorrhage, and mononuclear cell infiltration. Co-administration of nutrient metal mixture reversed the Pb-induced cardiac impairments as reflected in the recovery of the chosen sensitive markers of oxidative stress, reduced Pb levels and cardiac tissue changes. In conclusion, the data demonstrate that early-life exposure to Pb continuously influence the cardiac mitochondrial functions from early life to older age and further suggesting that adequate intake of nutrient metals may be potential therapeutic treatment for Pb intoxication.

Keywords

Lead exposure Long-term effect Essential nutrient metals Oxidative stress Mitochondria Aging rats 

Notes

Acknowledgements

This study was supported by Council of Scientific and Industrial Research (CSIR), Grant No. 37 (1349)/08/EMR-II.

Compliance with ethical standards

Conflict of interest

There are no conflicts of interest to declare.

References

  1. 1.
    Ettinger, A. S., Leonard, M. L., & Mason, J. (2019). CDC’s lead poisoning prevention program: A long-standing responsibility and commitment to protect children from lead exposure. Journal of Public Health Management and Practics, 25, S5–S12.CrossRefGoogle Scholar
  2. 2.
    Praveen, Sharma, Chambial, Shailja, & Shukla, Kamla Kant. (2015). Lead and neurotoxicity. Indian Journal of Clinical Biochemistry, 30(1), 1–2.CrossRefGoogle Scholar
  3. 3.
    Reddy, G. R., Devi, C. B., & Chetty, C. S. (2007). Developmental lead neurotoxicity: Alterations in brain cholinergic system. Neurotoxicology, 28, 402–407.CrossRefPubMedGoogle Scholar
  4. 4.
    Shvachiy, L., Geraldes, V., Amaro-Leal, Â., & Rocha, I. (2018). Intermittent low-level lead exposure provokes anxiety, hypertension, autonomic dysfunction and neuroinflammation. Neurotoxicology, 69, 307–319.CrossRefPubMedGoogle Scholar
  5. 5.
    Xu, X., Byles, J. E., Shi, Z., & Hall, J. J. (2018). Dietary patterns, dietary lead exposure and hypertension in the older Chinese population. Asia Pacific Journal of Clinical Nutrition, 27(2), 451–459.PubMedGoogle Scholar
  6. 6.
    Vaziri, N. D., & Gonick, H. C. (2015). Cardiovascular effects of lead exposure. Indian Journal of Medical Research, 128(4), 426–435.Google Scholar
  7. 7.
    Silva, M. A., de Oliveira, T. F., Almenara, C. C., Broseghini-Filho, G. B., Vassallo, D. V., Padilha, A. S., et al. (2015). Exposure to a low lead concentration impairs contractile machinery in rat cardiac muscle. Biological Trace Element Research, 167(2), 280–287.CrossRefPubMedGoogle Scholar
  8. 8.
    Ahmed, M. A., Khaled, M. A., & Hassanein, (2013). Cardio protective effects of Nigella sativa oil on lead induced cardio toxicity: Anti inflammatory and antioxidant mechanism. Journal of Physiol and Pathophysiol, 4(5), 72–80.CrossRefGoogle Scholar
  9. 9.
    Roshan, V. D., Assali, M., Moghaddam, A. H., Hosseinzadeh, M., & Myers, J. (2011). Exercise training and antioxidants: Effects on rat heart tissue exposed to lead acetate. International Journal of Toxicology, 30(2), 190–196.CrossRefPubMedGoogle Scholar
  10. 10.
    Basha, D. C., Basha, S. S., & Reddy, G. R. (2012). Lead-induced cardiac and hematological alterations in aging Wistar male rats: Alleviating effects of nutrient metal mixture. Biogerontology, 13(4), 359–368.CrossRefPubMedGoogle Scholar
  11. 11.
    Silveira, E. A., Siman, F. D., de Oliveira, F. T., Vescovi, M. V., Furieri, L. B., Lizardo, J. H., et al. (2014). Low-dose chronic lead exposure increases systolic arterial pressure and vascular reactivity of rat aortas. Free Radical Biology and Medicine, 67, 366–376.CrossRefPubMedGoogle Scholar
  12. 12.
    Carmignani, M., Volpe, A. R., Boscolo, P., Qiao, N., Di Gioacchino, M., Grilli, A., et al. (2000). Catcholamine and nitric oxide systems as targets of chronic lead exposure in inducing selective functional impairment. Life Sciences, 68, 401–415.CrossRefPubMedGoogle Scholar
  13. 13.
    Ferreira de Mattos, G., Costa, C., Savio, F., Alonso, M., & Nicolson, G. L. (2017). Lead poisoning: Acute exposure of the heart to lead ions promotes changes in cardiac function and Cav1.2 ion channels. Biophysics Reviews, 9(5), 807–825.CrossRefGoogle Scholar
  14. 14.
    Lanphear, B. P., Rauch, S., Auinger, P., Allen, R. W., & Hornung, R. W. (2018). Low-level lead exposure and mortality in US adults: A population-based cohort study. Lancet Public Health., S2468–2667(18), 30025–30027.Google Scholar
  15. 15.
    Park, S. K., Schwartz, J., Weisskopf, M., Sparrow, D., Vokonas, P. S., Wright, R. O., et al. (2006). Low-level lead exposure, metabolic syndrome, and heart rate variability: The VA Normative Aging Study. Environmental Health Perspectives, 114(11), 1718–1724.CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Prasanthi, R. P., Devi, C. B., Basha, D. C., Reddy, N. S., & Reddy, G. R. (2010). Calcium and zinc supplementation protects lead (Pb)-induced perturbations in antioxidant enzymes and lipid peroxidation in developing mouse brain. International Journal of Developmental Neuroscience, 28(2), 161–167.CrossRefPubMedGoogle Scholar
  17. 17.
    Park, S. K., Hu, H., Wright, R. O., Schwartz, J., Cheng, Y., Sparrow, D., et al. (2009). Iron metabolism genes, low-level lead exposure, and QT interval. Environmental Health Perspectives, 117(1), 80–85.CrossRefPubMedGoogle Scholar
  18. 18.
    Srikanthan, T. N., & Krishnamurthi, C. R. (1955). Tetrazolium test for dehydrogenases. Journal of Scientific & Industrial Research, 14, 206.Google Scholar
  19. 19.
    Gottipolu, R. R., Wallenborn, J. G., Karoly, E. D., Schladweiler, M. C., Ledbetter, A. D., Krantz, T., et al. (2009). One-month diesel exhaust inhalation produces hypertensive gene expression pattern in healthy rats. Environmental Health Perspectives, 17, 39–46.Google Scholar
  20. 20.
    Manual, Worthington. (2004). Xanthine Oxidase Assay (pp. 399–401). USA: Worthington Biochemical Corporation.Google Scholar
  21. 21.
    Korenberg, A., & Pricer, W. E., Jr. (1951). Triphosphate pyridine nucleotide isocitric dehydrogenase in yeast. Journal of Biological Chemistry, 1951(189), 123–136.Google Scholar
  22. 22.
    Mastanaiah, S., Chengal Raju, D., & Swami, K. S. (1978). Circadian rhythmic activity of lipase in the scorpion. Heterometrus fulvipes (C Koch). Current Science, 47, 130–131.Google Scholar
  23. 23.
    Ohkawa, H., Ohishim, N., & Yagi, K. (1979). Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Analytical Biochemistry, 95(2), 351–358.CrossRefPubMedGoogle Scholar
  24. 24.
    Lowry, O. H., Rosenbrough, N. J., Farr, A. L., & Randall, R. J. (1951). Protein measurement with Folin-phenol reagent. Journal of Biological Chemistry, 193, 265–275.PubMedGoogle Scholar
  25. 25.
    Chen, C., Li, Q., Nie, X., Han, B., Chen, Y., Xia, F., et al. (2017). Association of lead exposure with cardiovascular risk factors and diseases in Chinese adults. Environmental Science and Pollution Research International, 24(28), 22275–22283.CrossRefPubMedGoogle Scholar
  26. 26.
    An, H. C., Sung, J. H., Lee, J., Sim, C. S., Kim, S. H., & Kim, Y. (2017). The association between cadmium and lead exposure and blood pressure among workers of a smelting industry: A cross-sectional study. Annals of Occupational and Environmental Medicine, 29, 47.CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Steinberg, D. (2009). The LDL modification of atherogenesis: An update. Journal of Lipid Research, 50, S376–S381.CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Meredith, P. A., Campbell, B. C., Moore, M. R., & Goldberg, A. (1977). The effects of industrial lead poisoning on cytochrome P450 mediated phenazone (antipyrine) hydroxylation. European Journal of Clinical Pharmacology, 12(3), 235–239.CrossRefPubMedGoogle Scholar
  29. 29.
    Kojima, M., Masui, T., Nemoto, K., & Degawa, M. (2004). Lead nitrate-induced development of hypercholesterolemia in rats: Sterol-independent gene regulation of hepatic enzymes responsible for cholesterol homeostasis. Toxicology Letters, 154(1–2), 35–44.CrossRefPubMedGoogle Scholar
  30. 30.
    Ademuyiwa, O., Ugbaja, R. N., Idumebor, F., & Adebawo, O. (2005). Plasma lipid profiles and risk of cardiovascular disease in occupational lead exposure in Abeokuta, Nigeria. Lipids in Health and Diseases, 4, 19.CrossRefGoogle Scholar
  31. 31.
    Ranasinghe, P., Wathurapatha, W. S., Ishara, M. H., Jayawardana, R., Galappatthy, P., Katulanda, P., et al. (2015). Effects of Zinc supplementation on serum lipids: A systematic review and meta-analysis. Nutrition & Metabolism (London)., 12, 26.CrossRefGoogle Scholar
  32. 32.
    Ece, A., Yiğitoğlu, M. R., Vurgun, N., Güven, H., & Işcan, A. (1999). Serum lipid and lipoprotein profile in children with iron deficiency anemia. Pediatrics International, 41(2), 168–173.CrossRefPubMedGoogle Scholar
  33. 33.
    McIntyre, T. M., & Hazen, S. L. (2010). Lipid oxidation and cardiovascular disease: Introduction to a review series. Circulation Research, 107(10), 1167–1169.CrossRefPubMedGoogle Scholar
  34. 34.
    Dewanjee, S., Sahu, R., Karmakar, S., & Gangopadhyay, M. (2013). Toxic effects of lead exposure in Wistar rats: Involvement of oxidative stress and the beneficial role of edible jute (Corchorus olitorius) leaves. Food and Chemical Toxicology, 55, 78–91.CrossRefPubMedGoogle Scholar
  35. 35.
    Madamanchi, N. R., & Runge, M. S. (2013). Redox signaling in cardiovascular health and disease. Free Radical Biology Medicine, 61, 473–501.CrossRefPubMedGoogle Scholar
  36. 36.
    Raghuvanshi, R., Aikim, K., Pushpa, B., Aparna, M., & Misra, K. (2007). Xanthine oxidase as a marker of myocardial infarction. Indian Journal of Clinical Biochemistry, 22(2), 90–92.CrossRefPubMedPubMedCentralGoogle Scholar
  37. 37.
    Kilikdar, D., Mukherjee, D., Mitra, E., Ghosh, A. K., Basu, A., Chandra, A. M., et al. (2011). Protective effect of aqueous garlic extract against lead-induced hepatic injury in rats. Indian Journal of Experimental Biology, 49(7), 498–510.PubMedGoogle Scholar
  38. 38.
    Arif Tasleem, J., Mudsser, A., Kehkashan, S., Arif, A., Inho, C., Qazi, M., et al. (2015). Heavy metals and human health: Mechanistic insight into toxicity and counter defense system of antioxidants. International Journal of Molecular Sciences, 16(12), 29592–29630.CrossRefGoogle Scholar
  39. 39.
    Holmgren, A., & Lu, J. (2010). Thioredoxin and thioredoxin reductase: Current research with special reference to human disease. Biochemical and Biophysical Research Communications, 396(1), 120–124.CrossRefPubMedGoogle Scholar
  40. 40.
    Horstkotte, J., Perisic, T., Schneider, M., Lange, P., Schroeder, M., Kiermayer, C., et al. (2011). Mitochondrial thioredoxin reductase is essential for early postischemic myocardial protection. Circulation, 124(25), 2892–2902.CrossRefPubMedGoogle Scholar
  41. 41.
    Conterato, G. M., Quatrin, A., Somacal, S., Ruviaro, A. R., Vicentini, J., Augusti, P. R., et al. (2014). Acute exposure to low lead levels and its implications on the activity and expression of cytosolic thioredoxin reductase in the kidney. Basic & Clinical Pharmacology & Toxicology, 114(6), 476–484.CrossRefGoogle Scholar
  42. 42.
    Parildar, H., Dogru-Abbasoglu, S., Mehmetçik, G., Ozdemirler, G., Koçak-Toker, N., & Uysal, M. (2008). Lipid peroxidation potential and antioxidants in the heart tissue of beta-alanine- or taurine-treated old rats. Journal of Nutritional Science and Vitaminology (Tokyo)., 54(1), 61–65.CrossRefPubMedGoogle Scholar
  43. 43.
    Possamai, F. P., Júnior, S. Á., Parisotto, E. B., Moratelli, A. M., Inácio, D. B., Garlet, T. R., et al. (2010). Antioxidant intervention compensates oxidative stress in blood of subjects exposed to emissions from a coal electric-power plant in South Brazil. Environmental Toxicology and Pharmacology, 30, 175–180.CrossRefPubMedGoogle Scholar
  44. 44.
    Rendón-Ramírez, A. L., Maldonado-Vega, M., Quintanar-Escorza, M. A., Hernández, G., Arévalo-Rivas, B. I., Zentella-Dehesa, A., et al. (2014). Effect of vitamin E and C supplementation on oxidative damage and total antioxidant capacity in lead-exposed workers. Environmental Toxicology and Pharmacology, 37(1), 45–54.CrossRefPubMedGoogle Scholar
  45. 45.
    Tocchi, A., Quarles, E. K., Basisty, N., Gitari, L., & Rabinovitch, P. S. (2015). Mitochondrial dysfunction in cardiac aging. Biochimica et Biophysica Acta, 1847(11), 1424–1433.CrossRefPubMedPubMedCentralGoogle Scholar
  46. 46.
    Cantu, D., Fulton, R. E., Drechsel, D. A., & Patel, M. (2011). Mitochondrial aconitase knockdown attenuates paraquat-induced dopaminergic cell death via decreased cellular metabolism and release of iron and H2O2. Journal of Neurochemistry, 118(1), 79–92.CrossRefPubMedPubMedCentralGoogle Scholar
  47. 47.
    Vasquez-Vivar, J., Kalyanaraman, B., & Kennedy, M. C. (2000). Mitochondrial aconitase is a source of hydroxyl radical. An electron spin resonance investigation. Journal of Biological Chemistry, 275(19), 14064–14069.CrossRefPubMedGoogle Scholar
  48. 48.
    Yarian, S. C., Dikran, T., & Rajindar, S. S. (2006). Aconitase is the main functional target of aging in the citric acid cycle of kidney mitochondria from mice. Mechanisms of Ageing and Development, 127(1), 79–84.CrossRefPubMedGoogle Scholar
  49. 49.
    Ahamed, M., & Siddiqui, M. K. (2007). Environmental lead toxicity and nutritional factors. Clinical Nutrition, 26(4), 400–408.CrossRefPubMedGoogle Scholar
  50. 50.
    De Caterina, R., Zampolli, A., Del Turco, S., Madonna, R., & Massaro, M. (2006). Nutritional mechanisms that influence cardiovascular disease. American Journal of Clinical Nutrition, 83(2), 421S–426S.CrossRefPubMedGoogle Scholar
  51. 51.
    Mythili, Sabesan, & Malathi, Narasimhan. (2015). Diagnostic markers of acute myocardial infarction. Biomedical Reports, 3(6), 743–748.CrossRefPubMedPubMedCentralGoogle Scholar
  52. 52.
    Ghosh, D., Mitra, E., Firdaus, S. B., Ghosh, K. B., Chattopadhyay, A., Pattari, K. S., et al. (2013). Melatonin protects against lead-induced cardio toxicity: Involvement of antioxidant mechanism. International Journal of Pharmacy and Pharmaceutical Sciences, 5(3), 806–813.Google Scholar
  53. 53.
    Navas-Acien, A., Guallar, E., Silbergeld, E. K., & Rothenberg, S. J. (2007). Lead exposure and cardiovascular disease—A systematic review. Environmental Health Perspectives, 115(3), 472–482.CrossRefPubMedGoogle Scholar
  54. 54.
    D’Souza, H. S., Menezes, G., & Venkatesh, T. (2003). Role of essential trace minerals on the absorption of heavy metals with special reference to lead. Indian Journal of Clinical Biochemistry, 18(2), 154–160.CrossRefPubMedPubMedCentralGoogle Scholar
  55. 55.
    Dorea, J. G., & Donangelo, C. M. (2006). Early (in uterus and infant) exposure to mercury and lead. Clinical Nutrition, 25(3), 369–376.CrossRefPubMedGoogle Scholar
  56. 56.
    Nie, H., Sánchez, B. N., Wilker, E., Weisskopf, M. G., Schwartz, J., Sparrow, D., et al. (2009). Bone lead and endogenous exposure in an environmentally exposed elderly population: thenormative aging study. Journal of Occupational and Environmental Medicine, 51(7), 848–857.CrossRefPubMedPubMedCentralGoogle Scholar

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© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Chand Basha Davuljigari
    • 1
    Email author
  • Rajarami Reddy Gottipolu
    • 1
  1. 1.Department of ZoologySri Venkateswara UniversityTirupatiIndia

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