nach oben

Cardiovascular Toxicology

Erschienen in:

09.11.2022

Methylmercury Toxicity During Heart Development: A Combined Analysis of Morphological and Functional Parameters

verfasst von: Nathália Ronconi-Krüger, Jacqueline Pinheiro, Carmen Simioni, Evelise Maria Nazari

Erschienen in: Cardiovascular Toxicology | Ausgabe 12/2022

Einloggen, um Zugang zu erhalten

Abstract

The heart of higher vertebrates develops early as a tubular structure, which requires cellular and molecular events for proliferation, differentiation and apoptosis for growth, and individualization of cardiac chambers. Exposure to different stressors can cause disturbances in the normal development and functionality of the cardiovascular system. This study aimed to characterize the impact of methylmercury (MeHg) on heart development, specifically related to tissue morphology and parameters of vascular integrity and contractility, also focusing on cell cycle and apoptosis, using Gallus domesticus embryos as a model. The results showed morphological alterations, reduction in the thickness of the ventricular walls, and trabeculae changes in the hearts of embryos exposed to 0.1 µg MeHg/50 µL saline solution. These impacts were associated with increased contents of proteins related to cell cycle arrest and reduced cardiomyocyte proliferation. In addition, the contents of endothelial mediators for contractility and vascular integrity were imbalanced. The quantity and morphology of mitochondria of cardiomyocytes were injured. Together, these negative measurements impacted the reduction of heartbeats. In general, the parameters identified here demonstrate the relevance of combined molecular cellular tissue and physiological diagnosis for a better understanding of the cardiotoxicity of MeHg during development.

Fillion, M., Mergler, D., Passos, C. J. S., Larribe, F., Lemire, M., & Guimarães, J. R. D. (2006). A preliminary study of mercury exposure and blood pressure in the Brazilian Amazon. Environmental Health, 5(1), 1–9. https://doi.org/10.1186/1476-069X-5-29CrossRef

Afridi, H. I., Kazi, T. G., Talpur, F. N., Kazi, A., Arain, S. S., Arain, S. A., Brahman, K. D., & Panhwar, A. H. (2014). Interaction between selenium and mercury in biological samples of Pakistani myocardial infarction patients at different stages as related to controls. Biological Trace Element Research, 158(2), 143–151. https://doi.org/10.1007/s12011-014-9932-8CrossRefPubMed

Valera, B., Suhas, E., Counil, E., Poirier, P., & Dewailly, E. (2014). Influence of polyunsaturated fatty acids on blood pressure, resting heart rate and heart rate variability among French Polynesians. Journal of the American College of Nutrition, 33(4), 288–296. https://doi.org/10.1080/07315724.2013.874913CrossRefPubMed

Morel, F. M., Kraepiel, A. M., & Amyot, M. (1998). The chemical cycle and bioaccumulation of mercury. Annual Review of Ecology and Systematics, 29, 543–566.CrossRef

Mahaffey, K. R. (1999). Methylmercury: A new look at the risks. Public Health Reports, 114(5), 396.PubMedPubMedCentral

Sørensen, N., Murata, K., Budtz-Jørgensen, E., Weihe, P., & Grandjean, P. (1999). Prenatal methylmercury exposure as a cardiovascular risk factor at seven years of age. Epidemiology, 10, 370–375.CrossRefPubMed

Grandjean, P., Murata, K., Budtz-Jørgensen, E., & Weihe, P. (2004). Cardiac autonomic activity in methylmercury neurotoxicity: 14-year follow-up of a Faroese birth cohort. The Journal of pediatrics, 144(2), 169–176. https://doi.org/10.1016/j.jpeds.2003.10.058CrossRefPubMed

Choi, A. L., Weihe, P., Budtz-Jørgensen, E., Jørgensen, P. J., Salonen, J. T., Tuomainen, T. P., Murata, K., Nielsen, H. P., Petersen, M. S., Askham, J., & Grandjean, P. (2009). Methylmercury exposure and adverse cardiovascular effects in Faroese whaling men. Environmental Health Perspectives, 117(3), 367–372. https://doi.org/10.1289/ehp.11608CrossRefPubMed

Faria, T. D., Simões, M. R., Vassallo, D. V., Forechi, L., Almenara, C. C., Marchezini, B. A., Stefanon, I., & Vassallo, P. F. (2018). Xanthine oxidase activation modulates the endothelial (vascular) dysfunction related to HgCl₂ exposure plus myocardial infarction in rats. Cardiovascular Toxicology, 18(2), 161–174. https://doi.org/10.1007/s12012-017-9427-xCrossRefPubMed

10.

Jin, X., Hidiroglou, N., Lok, E., Taylor, M., Kapal, K., Ross, N., Sarafin, K., Lau, A., De Souza, A., Chan, H. M., & Mehta, R. (2012). Dietary selenium (Se) and vitamin E (VE) supplementation modulated methylmercury-mediated changes in markers of cardiovascular diseases in rats. Cardiovascular Toxicology, 12(1), 10–24. https://doi.org/10.1007/s12012-011-9134-yCrossRefPubMed

11.

Fardin, P. B. A., Simões, R. P., Schereider, I. R. G., Almenara, C. C. P., Simões, M. R., & Vassallo, D. V. (2020). Chronic mercury exposure in prehypertensive SHRs accelerates hypertension development and activates vasoprotective mechanisms by increasing NO and H2O2 production. Cardiovascular Toxicology, 20(3), 197–210. https://doi.org/10.1007/s12012-019-09545-6CrossRefPubMed

12.

Al Naieb, S., Happel, C. M., & Yelbuz, T. M. (2013). A detailed atlas of chick heart development in vivo. Annals of Anatomy-Anatomischer Anzeiger, 195(4), 324–341. https://doi.org/10.1016/j.aanat.2012.10.011CrossRef

13.

Martinsen, B. J. (2005). Reference guide to the stages of chick heart embryology. Developmental Dynamics: An Official publication of the American Association of Anatomists, 233(4), 1217–1237. https://doi.org/10.1002/dvdy.20468CrossRef

14.

Yutzey, K. E., Gannon, M., & Bader, D. (1995). Diversification of cardiomyogenic cell lineages in vitro. Developmental Biology, 170(2), 531–541. https://doi.org/10.1006/dbio.1995.1234CrossRefPubMed

15.

Gessert, S., & Kuhl, M. (2010). The multiple phases and faces of wnt signaling during cardiac differentiation and development. Circulation Research, 107(2), 186–199. https://doi.org/10.1161/CIRCRESAHA.110.221531CrossRefPubMed

16.

Wu, M. (2018). Mechanisms of trabecular formation and specification during cardiogenesis. Pediatric Cardiology, 39(6), 1082–1089. https://doi.org/10.1007/s00246-018-1868-xCrossRefPubMedPubMedCentral

17.

Lopaschuk, G. D., Collins-Nakai, R. L., & Itoi, T. (1992). Developmental changes in energy substrate use by the heart. Cardiovascular Research, 26(12), 1172–1180. https://doi.org/10.1093/cvr/26.12.1172CrossRefPubMed

18.

Gao, Y., & Raj, J. U. (2010). Regulation of the pulmonary circulation in the fetus and newborn. Physiological Reviews, 90(4), 1291–1335. https://doi.org/10.1152/physrev.00032.2009CrossRefPubMed

19.

Huss, J. M., & Kelly, D. P. (2005). Mitochondrial energy metabolism in heart failure: A question of balance. The Journal of Clinical Investigation, 115(3), 547–555. https://doi.org/10.1172/JCI24405CrossRefPubMedPubMedCentral

20.

Palaniyandi, S. S., Qi, X., Yogalingam, G., Ferreira, J. C. B., & Mochly-Rosen, D. (2010). Regulation of mitochondrial processes: A target for heart failure. Drug Discovery Today: Disease Mechanisms, 7(2), e95–e102. https://doi.org/10.1016/j.ddmec.2010.07.002CrossRefPubMed

21.

Men, H., Cai, H., Cheng, Q., Zhou, W., Wang, X., Huang, S., Zheng, Y., & Cai, L. (2021). The regulatory roles of p53 in cardiovascular health and disease. Cellular and Molecular Life Sciences, 78(5), 2001–2018. https://doi.org/10.1007/s00018-020-03694-6CrossRefPubMed

22.

Tzahor, E., & Poss, K. D. (2017). Cardiac regeneration strategies: Staying young at heart. Science, 356(6342), 1035–1039. https://doi.org/10.1126/science.aam5894CrossRefPubMedPubMedCentral

23.

Shimizu, I., & Minamino, T. (2019). Cellular senescence in cardiac diseases. Journal of Cardiology, 74(4), 313–319. https://doi.org/10.1016/j.jjcc.2019.05.002CrossRefPubMed

24.

Zhang, Y. H. (2016). Neuronal nitric oxide synthase in hypertension–an update. Clinical Hypertension, 22(1), 1–7. https://doi.org/10.1186/s40885-016-0055-8CrossRef

25.

Carnicer, R., Crabtree, M. J., Sivakumaran, V., Casadei, B., & Kass, D. A. (2013). Nitric oxide synthases in heart failure. Antioxidants & Redox Signaling, 18(9), 1078–1099. https://doi.org/10.1089/ars.2012.4824CrossRef

26.

Heinzel, F. R., Hohendanner, F., Jin, G., Sedej, S., & Edelmann, F. (2015). Myocardial hypertrophy and its role in heart failure with preserved ejection fraction. Journal of Applied Physiology, 119(10), 1233–1242. https://doi.org/10.1152/japplphysiol.00374.2015CrossRefPubMed

27.

Kaptoge, S., Pennells, L., De Bacquer, D., Cooney, M. T., Kavousi, M., Stevens, G., Riley, L. M., Savin, S., Khan, T., Altay, S., Amouyel, P., et al. (2019). World Health Organization cardiovascular disease risk charts: revised models to estimate risk in 21 global regions. The Lancet Global Health, 7(10), e1332–e1345. https://doi.org/10.1016/S2214-109X(19)30318-3CrossRef

28.

Carvalho, M. C., Nazari, E. M., Farina, M., & Muller, Y. M. (2008). Behavioral, morphological, and biochemical changes after in ovo exposure to methylmercury in chicks. Toxicological Sciences, 106(1), 180–185. https://doi.org/10.1093/toxsci/kfn158CrossRefPubMed

29.

Garcia-Martinez, V., & Schoenwolf, G. C. (1993). Primitive-streak origin of the cardiovascular system in avian embryos. Developmental Biology, 159(2), 706–719. https://doi.org/10.1006/dbio.1993.1276CrossRefPubMed

30.

Cohen-Gould, L., & Mikawa, T. (1996). The fate diversity of mesodermal cells within the heart field during chicken early embryogenesis. Developmental Biology, 177(1), 265–273. https://doi.org/10.1006/dbio.1996.0161CrossRefPubMed

31.

Shires, S. E., & Gustafsson, Å. B. (2015). Mitophagy and heart failure. Journal of Molecular Medicine, 93(3), 253–262. https://doi.org/10.1007/s00109-015-1254-6CrossRefPubMed

32.

Zhou, B., & Tian, R. (2018). Mitochondrial dysfunction in pathophysiology of heart failure. The Journal of Clinical Investigation, 128(9), 3716–3726. https://doi.org/10.1172/JCI120849CrossRefPubMedPubMedCentral

33.

Gray, D. A., & Woulfe, J. (2005). Lipofuscin and aging: A matter of toxic waste. Science of Aging Knowledge Environment. https://doi.org/10.1126/sageke.2005.5.re1CrossRefPubMed

34.

Takemura, G., Kanamori, H., Okada, H., Tsujimoto, A., Miyazaki, N., Takada, C., Hotta, Y., Takatsu, Y., Fujiwara, T., & Fujiwara, H. (2017). Ultrastructural aspects of vacuolar degeneration of cardiomyocytes in human endomyocardial biopsies. Cardiovascular Pathology, 30, 64–71. https://doi.org/10.1016/j.carpath.2017.06.012CrossRefPubMed

35.

Fellet, A. L., Boveris, A. E., Arranz, C. T., & Balaszczuk, A. M. (2008). Cardiac mitochondrial nitric oxide: A regulator of heart rate? American Journal of Hypertension, 21(4), 377–381. https://doi.org/10.1038/ajh.2007.90CrossRefPubMed

36.

Marzabadi, M. R., & Jones, C. B. (1992). Heary metals and lipofuscinogenesis. A study on myocardial cells cultured under varying oxidative stress. Mechanisms of Ageing and Development, 66(2), 159–171. https://doi.org/10.1016/0047-6374(92)90133-XCrossRefPubMed

37.

Ivy, G. O., & Gurd, J. W. (1988). A proteinase inhibitor model of lipofuscin formation. In: Zs-Nagy I (ed) Lipofuscin-1987: state of the art. (pp. 83–108). Elsevier.

38.

Terman, A., Dalen, H., Eaton, J. W., Neuzil, J., & Brunk, U. T. (2004). Aging of cardiac myocytes in culture: Oxidative stress, lipofuscin accumulation, and mitochondrial turnover. Annals of the New York Academy of Sciences, 1019(1), 70–77. https://doi.org/10.1196/annals.1297.015CrossRefPubMed

39.

Dos Santos, A. A., Hort, M. A., Culbreth, M., López-Granero, C., Farina, M., Rocha, J. B., & Aschner, M. (2016). Methylmercury and brain development: A review of recent literature. Journal of Trace Elements in Medicine and Biology, 38, 99–107. https://doi.org/10.1016/j.jtemb.2016.03.001CrossRefPubMedCentral

40.

Ou, Y. C., White, C. C., Krejsa, C. M., Ponce, R. A., Kavanagh, T. J., & Faustman, E. M. (1999). The role of intracellular glutathione in methylmercury-induced toxicity in embryonic neuronal cells. Neurotoxicology, 20(5), 793–804.PubMed

41.

Franco, J. L., Posser, T., Dunkley, P. R., Dickson, P. W., Mattos, J. J., Martins, R., Bainy, A. C., Marques, M. R., Dafre, A. L., & Farina, M. (2009). Methylmercury neurotoxicity is associated with inhibition of the antioxidant enzyme glutathione peroxidase. Free Radical Biology and Medicine, 47(4), 449–457. https://doi.org/10.1016/j.freeradbiomed.2009.05.013CrossRefPubMed

42.

Thompson, S. A., White, C. C., Krejsa, C. M., Eaton, D. L., & Kavanagh, T. J. (2000). Modulation of glutathione and glutamate-L-cysteine ligase by methylmercury during mouse development. Toxicological Sciences, 57(1), 141–146. https://doi.org/10.1093/toxsci/57.1.141CrossRefPubMed

43.

Stringari, J., Nunes, A. K., Franco, J. L., Bohrer, D., Garcia, S. C., Dafre, A. L., Milatovic, D., Souza, D. O., Rocha, J. B., Aschner, M., & Farina, M. (2008). Prenatal methylmercury exposure hampers glutathione antioxidant system ontogenesis and causes long-lasting oxidative stress in the mouse brain. Toxicology and Applied Pharmacology, 227(1), 147–154. https://doi.org/10.1016/j.taap.2007.10.010CrossRefPubMed

44.

Forte, M., Conti, V., Damato, A., Ambrosio, M., Puca, A. A., Sciarretta, S., Frati, G., Vecchione, C., & Carrizzo, A. (2016). Targeting nitric oxide with natural derived compounds as a therapeutic strategy in vascular diseases. Oxidative Medicine and Cellular Longevity. https://doi.org/10.1155/2016/7364138CrossRefPubMedPubMedCentral

45.

Shah, A. M. (1996). Paracrine modulation of heart cell function by endothelial cells. Cardiovascular Research, 31(6), 847–867. https://doi.org/10.1016/S0008-6363(96)00025-9CrossRefPubMed

46.

Sedmera, D., Hu, N., Weiss, K. M., Keller, B. B., Denslow, S., & Thompson, R. P. (2002). Cellular changes in experimental left heart hypoplasia. The Anatomical Record: An Official Publication of the American Association of Anatomists, 267(2), 137–145. https://doi.org/10.1002/ar.10098CrossRef

47.

Axelrod, J. D. (2020). Planar cell polarity signaling in the development of left–right asymmetry. Current Opinion in Cell Biology, 62, 61–69. https://doi.org/10.1016/j.ceb.2019.09.002CrossRefPubMed

48.

Zhang, M., Zhang, Y., Xu, E., Mohibi, S., de Anda, D. M., Jiang, Y., Zhang, J., & Chen, X. (2018). Rbm24, a target of p53, is necessary for proper expression of p53 and heart development. Cell Death & Differentiation, 25(6), 1118–1130. https://doi.org/10.1038/s41418-017-0029-8CrossRef

49.

Zhang, D., Li, Y., Heims-Waldron, D., Bezzerides, V., Guatimosim, S., Guo, Y., Gu, F., Zhou, P., Lin, Z., Ma, Q., Liu, J., Wang, D.-Z., & Pu, W. T. (2018). Mitochondrial cardiomyopathy caused by elevated reactive oxygen species and impaired cardiomyocyte proliferation. Circulation Research, 122(1), 74–87. https://doi.org/10.1161/CIRCRESAHA.117.311349CrossRefPubMed

50.

Picca, A., Mankowski, R. T., Burman, J. L., Donisi, L., Kim, J. S., Marzetti, E., & Leeuwenburgh, C. (2018). Mitochondrial quality control mechanisms as molecular targets in cardiac ageing. Nature Reviews Cardiology, 15(9), 543–554. https://doi.org/10.1016/S0008-6363(96)00025-9CrossRefPubMedPubMedCentral

Titel: Methylmercury Toxicity During Heart Development: A Combined Analysis of Morphological and Functional Parameters
verfasst von: Nathália Ronconi-Krüger
Jacqueline Pinheiro
Carmen Simioni
Evelise Maria Nazari
Publikationsdatum: 09.11.2022
Verlag: Springer US
Erschienen in: Cardiovascular Toxicology / Ausgabe 12/2022
Print ISSN: 1530-7905
Elektronische ISSN: 1559-0259
DOI: https://doi.org/10.1007/s12012-022-09772-4

Springer Medizin

Abstract

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten