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

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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.

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References

  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.

    Google Scholar 

  2. Praveen, Sharma, Chambial, Shailja, & Shukla, Kamla Kant. (2015). Lead and neurotoxicity. Indian Journal of Clinical Biochemistry,30(1), 1–2.

    Google Scholar 

  3. Reddy, G. R., Devi, C. B., & Chetty, C. S. (2007). Developmental lead neurotoxicity: Alterations in brain cholinergic system. Neurotoxicology,28, 402–407.

    CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    PubMed  Google Scholar 

  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. 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.

    CAS  PubMed  Google Scholar 

  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.

    Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    CAS  Google Scholar 

  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. 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.

    CAS  PubMed  PubMed Central  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  18. Srikanthan, T. N., & Krishnamurthi, C. R. (1955). Tetrazolium test for dehydrogenases. Journal of Scientific & Industrial Research,14, 206.

    Google Scholar 

  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. Manual, Worthington. (2004). Xanthine Oxidase Assay (pp. 399–401). USA: Worthington Biochemical Corporation.

    Google Scholar 

  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. 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. Ohkawa, H., Ohishim, N., & Yagi, K. (1979). Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Analytical Biochemistry,95(2), 351–358.

    CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    PubMed  PubMed Central  Google Scholar 

  27. Steinberg, D. (2009). The LDL modification of atherogenesis: An update. Journal of Lipid Research,50, S376–S381.

    PubMed  PubMed Central  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    Google Scholar 

  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.

    Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  33. McIntyre, T. M., & Hazen, S. L. (2010). Lipid oxidation and cardiovascular disease: Introduction to a review series. Circulation Research,107(10), 1167–1169.

    CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  35. Madamanchi, N. R., & Runge, M. S. (2013). Redox signaling in cardiovascular health and disease. Free Radical Biology Medicine,61, 473–501.

    CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  PubMed Central  Google Scholar 

  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.

    PubMed  Google Scholar 

  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.

    Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    CAS  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    PubMed  Google Scholar 

  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.

    CAS  PubMed  PubMed Central  Google Scholar 

  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.

    CAS  PubMed  PubMed Central  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  49. Ahamed, M., & Siddiqui, M. K. (2007). Environmental lead toxicity and nutritional factors. Clinical Nutrition,26(4), 400–408.

    CAS  PubMed  Google Scholar 

  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.

    PubMed  Google Scholar 

  51. Mythili, Sabesan, & Malathi, Narasimhan. (2015). Diagnostic markers of acute myocardial infarction. Biomedical Reports,3(6), 743–748.

    PubMed  PubMed Central  Google Scholar 

  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.

    CAS  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    PubMed  PubMed Central  Google Scholar 

  55. Dorea, J. G., & Donangelo, C. M. (2006). Early (in uterus and infant) exposure to mercury and lead. Clinical Nutrition,25(3), 369–376.

    CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

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

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Davuljigari, C.B., Gottipolu, R.R. Late-life Cardiac Injury in Rats following Early Life Exposure to Lead: Reversal Effect of Nutrient Metal Mixture. Cardiovasc Toxicol 20, 249–260 (2020). https://doi.org/10.1007/s12012-019-09549-2

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