Abstract
Manganese (Mn)-induced Parkinsonism has been well documented; however, little attention has been devoted to Mn-induced cardiovascular dysfunction. This review summarizes literature data from both animal and human studies on Mn’s effect on cardiovascular function. Clinical and epidemiological evidence suggests that the incidence of abnormal electrocardiogram (ECG) is significantly higher in Mn-exposed workers than that in the control subjects. The main types of abnormal ECG include sinus tachycardia, sinus bradycardia, sinus arrhythmia, sinister megacardia, and ST-T changes. The accelerated heart-beat and shortened P-R interval appear to be more prominent in fermale exposed workers than in their male counterparts. Mn-exposed workers display a mean diastolic blood pressure that is significantly lower than that of the control subjects, especially in the young and female exposed workers. Animal studies indicate that Mn is capable of quickly accumulating in heart tissue, resulting in acute or sub-acute cardiovascular disorders, such as a cute cardio-depression and hypotension. These toxic outcomes appear to be associated with Mn-induced mitochondrial damage and interaction with the calcium channel in the cardiovascular system.
Similar content being viewed by others
References
Mena, I. (1980). Managanese. In: Metals in the Environment (Waldrom, H.E., ed.) Academic, London: pp. 199–219.
Bencko, V., and Cikrt M. (1984). Manganese: a review of occupational and environmental toxicology. J. Hyg. Epidemiol. Microbiol. Immunol. 28:139–148.
Li, G.J., Zhang, L., Lu, L., Wu, P., and Zheng, W. (2004). Occupational exposure to welding fume among welders: alterations of manganese, iron, zinc, copper, and lead in body fluids and the oxidative stress status. J. Occup. Environ. Med. 46:241–248.
Davis, J.M., Jarabek, A.M., Mage, D.T., and Graham, J.A. (1999). Inhalation health risk assessment of MMT. Environ. Res. 80:103–104.
World Health Organization (WHO) (1981). Environmental health criteria 17: Manganese. Geneva: pp. 1–110.
Crossgrove, J., and Zheng, W. (2004). Manganese toxicity upon overexposure. NMR Biomed. 17:544–553.
Mergler, D., and Baldwin, M. (1997). Early manifestations of manganese neurotoxicity in humans: an update. Environ. Res. 73:92–100.
Aschner, M., Erikson, K.M., and Dorman, D.C. (2005). Manganese dosimetry: species differences and implications for neurotoxicity. Crit. Rev. Toxicol. 35:1–32.
Kobert R. (1883). Zur pharmakologie des mangans und eisens. Arch. Exp. Pathol. 16:361–392.
Schroeder, H.A., Perry, M.H., Dennis, G.E., and Mahoney, E.L. (1955). Pressor substances in arterial hypertension. V. Chemical and pharmacological characteristics of pherentasine. J. Exp. Med. 102:319–333.
Schroeder, H.A., and Perry, M.H. (1955). Antihypertensive effect of metal binding agents. J. Lab. Clin. Med. 46: 416–422.
Kostial, K., Landeka, M., and Slat, B. (1974). Manganese ions and synaptic transmission in the superior cervical ganglion of the cat. Brit. J. Pharmacol. 51:231–235.
Agata, N., Tanaka, H., and Shigenobu, K. (1992). Effect of Mn2+ on neonatal and adult rat heart: initial depression and late augmentation of contractile force. Eur. J. Pharmacol. 222:223–226.
Zeng, X.H., Chi, Y.M., Dong, G.S., Wan, H.J., Liu, X.L., Zeng, S.J., et al. (1990). An experimental study of the excess manganese on the injured myocardium effect in rat raised with food from the disease area. J. Chinese Endemic Dis. 9:281–284.
Zeng, X.H., Wan, H.J., Ao, L.H., Qi, L., Chi, Y.M., Zeng, S.J., et al. (1991). A study of the relationship between the contents of Se, Mn dietary and myocardial injury. J. Hearbind Med. Univ. 25:255–258.
Sui, J.M., Zhou, B.C., Zeng, X.H., Zeng, S.J., and Yu, W.H. (1990). Effect of managanese on the mobility of mitochondrial membrane in rat myocardium. J. Chinese Endemic Dis. 9:277–280.
Charash, B., Placek, E., Sos, T.A., and Kligfield, P. (1982). Dose-related effects of manganese on the canine electro-cardiogram. J. Electrocardiol. 15:149–152.
Brurok, H., Berg, K., Sneen, L., Grant, D., Karlsson, J.O.G., and Jynge P. (1999). Cardiac metal contents after infusions of manganese: An experimental evaluation in the isolated rat heart. Invest. Radiol. 34:470–476.
Brurok, H., Schjott, J., Berg, K., and Karlsson, J.O.G. (1997). Mangenese and heart: acute cardiodepression and myocardial accumulation of manganese. Acta Physiol. Scand. 159:33–40.
Brurok, H., Schjott, J., Berg, K., Karlsson, J.O.G., and Jyunge, P. (1997). Effects of MnDPDP, DPDP-, and MnCl2 on cardiac energy metabolism and manganese accumulation. An experimental study in the isolated perfused rat heart. Invest. Radiol. 32:205–211.
Li, X.G., and Zhou, X.B. (1987). Effect of manganese on the electric activity in ventricle muscle and sinus cell. J. Chinese Endemic Dis. 6:67–70.
Jynge, P., Brurok, H., Schjott, J., Berg. K., and Karlsson, J.O.G. (1993). Physiologic effects of MnDPDP and MnCl2 in the isolated rat heart. Proceedings of the 12th meeting of the SMRM; New York, NY.
Brurok, H., Schiott, J., Berg, K., Karlsson, J.O.G., and Jynge, P. (1995) Effects of manganese dipyridoxyl diphosphate, dipyridoxyl diphosphate—, and manganese chloride on cardiac function. Invest. Radiol. 30:159–167.
Jynge, P., Asplund, A., Schjott, J. Towart, R., Karlsson, J.O.G., and Refsum, H. (1994). Cardiovascular effects of MnDPDP compared to MnCl2. Proceedings of the 2nd Meeting of the SMR, San Francisco, CA.
Wolf, G.L., and Baum, L. (1983). Cardiovascular toxicity and tissue proton T1 response to manganese injection in the dog and rabbit. Am. J. Radiol. 141:193–197.
Muggenburg, B.A., Benson, J.M., Barr, E.B., Kubatko, J., and Tilley, L.P. (2003). Short-term inhalation of particulate transition metals has little effect on the electrocardiograms of dogs having preexisting cardiac abnormalities. Inhal. Toxicol. 15:357–371.
Dudek, H., and Pytkowski, B. (1991). Effects of in vivo manganese administration on calcium exchange and contractile force of rat ventricular myocardium. Basic Res. Cardiol. 86:515–522.
Tanaka, H., Ishii, T., Fujisaki, R., Miyamoto, Y., Tanaka, Y., Aikawa, T., et al. (2002). Effect of manganese on guineapig ventricle: initial depression and late augmentation of contractile force. Biol. Pharm. Bull. 25:323–326.
Vander Elst, L., Colet, J.M., and Muller, R.N. (1997). Spectroscopic and metabolic effects of MnCl2 and MnDPDP on the isolated and perfused rat heart. Invest. Radiol. 32: 581–588.
Khan, K.N., Andress, J.M., and Smith, P.F. (1997). Toxicity of subacute intravenous manganese chloride administration in beagle dogs. Toxicol. Pathol. 25:344–350.
Yan, M., Liu, D.L., Chua, Y.L., Chen, C., and Lim, Y.L. (2001). Effects of micromolar concentration of manganese, copper, and zinc on α1-adrenoceptor-mediating contraction in rat aorta. Biol. Trace Elem. Res. 82:159–166.
Kalea, A.Z., Harris, P.D., and Klimis-Zacas, D.J. (2005). Dietary manganese suppresses alphal adrenergic receptor-mediated vascular contraction. J. Nutr. Biochem. 16: 44–49.
Brock, A.A., Chapman, S.A., Ulman, E.A., and Wu, G., (1994). Dietary manganese deficiency decrease rat hepatic arginase activity. J. Nutr. 124:340–344.
Ensunsa, J.L., Symons, J.D., Lanoue, L., Schrader, H.R., and Keen, C.L. (2004). Reducing arginase activity via die-tary manganese deficiency enhances endothelium-dependent vasorelaxation of rat aorta. Exp. Biol. Med. 229:1143–1153.
Karlsson, J.O.G., Mortensen, E., Pedersen, H.K., Sager, G., and Refsum, H. (1997). Cardiovascular effects of MnDPDP and MnC12 in dogs with acute ischaemic heart failure. Acta Radiol. 38:750–758.
Jynge, P., Brurok, H., Asplund, A., Towart, R., Refssum, H., and Karlsson, J.O.G. (1997). Cardiovascular safety of MnDPDP and MnCl2. Acta Radiol. 38:740–749.
Jiang, Y.M., Lu, J.P., Tang, Y., Lu, Z.G., and Huang, J.L. (2000). Effects of low level manganese exposure on workers’ cardiovascular functions. Ind. Health Occup. Dis. 26: 28–30.
Jiang, Y.M., Lu, J.P., Lu, Z.G., and Huang, J.L. (1999). Effects of manganese exposure on female workers’ cardiovascular function. Railway Occup. Safety Health Environ. Prot. 26:31–33.
Xie, P.Y., Jiang, Y.M., Li, W.P., Yang, D.P., Yin, X.X., and Chen, L.H. (1999). Studies on changes of electrocardiogram and blood pressure in exposed workers. China Occup. Med. 26:21–23.
Zhang S.Q., Meng, X.M., and Xing, Z.F. (2003). The effect of long-term exposure to manganese smoke and dust on cardiovascular system in workers. J. Practical. Electrocardiol. 12:204–205.
Ji Q, and Zhang B. (2004). Alteration of the electrocardio-gram in workers exposed to low level manganese. Jiangsu Prev. Med. 15:50–51.
Jiang, Y.M., Xie, P.Y., Lu, J.P., Luo, J.R., Kong, X.C., and Chen, J.X. (1999). Investigation on cardiovascular functions in milling workers exposed to manganese dust. Railway Occup. Safety Health Environ. Prot. 6:179–182.
Su, D.M., Li, J.Y., Liu, S.Z., and Guo, G.X. (1998). Investigation on health in manganese ferroalloy workers. Occup. Health Emerg. Rescue 16, 148–149.
Hobbesland, A., Kjuus, H., and Thelle, D.S. (1997). Mortality from cardiovascular disease and sudden death in ferroalloy plants. Scand J. Work Environ. Health 23: 334–341.
Sjogren, B. (1998). A possible connection between funace dust exposure, plasma fibrinogen levels and cardiovascular disease. Scand J. Work Environ. Health 24:236–237.
Misselwitz, B., Muhler, A., and Weinmann, H.J. (1995). A toxicologic risk for using manganese complexes? A literature survey of existing data through several medical specialites. Invest. Radiol. 30:611–620.
Jiang, Y.M., Lu, J.P., Huang, Z.B., Lu, Z.G., Huang, J.L., and Huang H.H. (2002). Effects of manganese exposure on cardiovascular functions of male workers. Ind. Health Occup. Dis. 28:65–67.
Saric, M., and Hrustic, O. (1975). Exposure to airborne manganese and arterial blood pressure. Environ. Res. 10: 314–318.
Barrington, W.W., Angle, C.R., Willcockson, N.K., Padula, M.A., and Korn, T. (1998). Autonomic function in manganese alloy workers. Environ. Res. 78:50–58.
He, S.C., Niu, Q., Wang, S., Chen, Y.L., Li, H.Y., and Wang, J.Y. (2002). Alteration of cardiovascular autonomic nervous system in welding workers. Chin. J. Environ. Occup. Med. 19:371–373.
Magari, S.R., Schwartz, J., Williams, P.L., Hauser, R., Smith, T.J., and Christiani, D.C. (2002). The association of particulate air metal concentrations with heart rate variability. Environ. Health Perspect. 110:875–880.
Lu, J.F. (1989). Applied value on cardiac STI in the examination of the workers exposed to lead, benzene and manganese. Guangxi Occup. Prev. 9:66.
Reaney, S.H., and Smith, D.R. (2005). Manganese oxidation state mediates toxicity in PC12 cells. Toxicol. Appl. Pharmacol. 205:271–281.
Sun G.F. (2003). Manganese. In: Occupational Health and Occupational Medicine, 5th Ed. (Jin, T.Y. and Sun G.F., eds.) People Press, Beijing: pp. 175–176.
Franco Mdo, C., Dantas, A.P., Akamine, E.H., Kawamoto E.M., Fortes, Z.B., Scavone, C., et al. (2002). Enhanced oxidative stress as a potential mechanism underlying the programming of hypertension in utero. J. Cardiovasc. Pharmacol. 40:501–509.
Xuan D.F., Chu, J.H., Li, G.J., Geng, R., and Li, J. (2004). Effects of manganese with different valence on SOD activity in brain, liver and heart of rats. Ind. Health Occup. Dis. 30, 83–86.
Ramos, K.S., Chacon, E., Daniel, and Acosta, J. (1996). Toxic responses of the heart and vascular systems. In: Casarett and Doull’s Toxicology: The Basic Science of Poisons 5th Ed. (Klaassen C.D. ed.) McGraw-Hill, New York: pp. 487–527.
Hamai, D., and Bony, S.C. (2004). Oxidative basis of manganese neurotoxicity. Ann. N.Y. Acad. Sci. 1012:129–141.
Zheng, W., Ren, S., and Graziano, J.H. (1998). Manganese inhibits mitochondrial aconitase: A mechanism of manganese neurotoxicity. Brain Res. 799:334–342.
Zhao, F., Li, G.J., Chu, J.H., Cai, S., Geng, R., Wu, P., et al. (2003). Effects of manganese on the myocardial mitrochondrial function in old rats. Chin. J. Environ. Occup. Med. 20:151–153, 158.
Verity, M.A. (1999). Manganese neurotoxicity: a mechanistic hypothesis. Neurotoxicology 20:489–497.
Malecki, E.A. (2001). Manganese toxicity is associated with mitochondrial dysfunction and DNA fragmentation in rat primary striatal neurons. Brain Res. Bull. 55:225–228.
Brown, S., and Taylor, N.L. (1999). Could Mitochondrial dysfunction play a role in manganese toxicity? Environ. Toxicol. Pharmacol. 7:49–57.
Gavin, C.E., Gunter, K.K., and Gunter, T.E. (1999). Manganese and calcium transport in mitochondria: implications for manganese toxicity. Neurotoxicology 20:445–454.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Jiang, Y., Zheng, W. Cardiovascular toxicities upon managanese exposure. Cardiovasc Toxicol 5, 345–354 (2005). https://doi.org/10.1385/CT:5:4:345
Received:
Revised:
Accepted:
Issue Date:
DOI: https://doi.org/10.1385/CT:5:4:345