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ARS Home » Plains Area » Grand Forks, North Dakota » Grand Forks Human Nutrition Research Center » Healthy Body Weight Research » Research » Publications at this Location » Publication #147694
Title: LETTER TO THE EDITOR: INHALED ZINC MAY INDUCE COPPER DEFICIENCY

Author
item Klevay, Leslie

Submitted to: Toxicological Sciences
Publication Type: Other
Publication Acceptance Date: 4/3/2003
Publication Date: 7/1/2003
Citation: Klevay, L.M. Inhaled zinc may induce copper deficiency [Letter to Editor]. Toxicological Sciences. 2003. 74:228-230.

Interpretive Summary: Kodavanti et al. induced cardiomyopathy in Wistar Kyoto rats by inhalation exposure to environmental combustion particles similar to ambient particulate matter and rich in bioavailable zinc. Myocardial degeneration, inflammation and fibrosis were prominent. No direct, mechanistic data were available. The only mechanism known by which zinc intoxication produces pathology is by the induction of copper deficiency. This antagonism has been known for nearly 60 years; some of the numerous animal species victimized have been reviewed. Copper deficiency, whether induced by a diet low in copper or by excess zinc, induces a wide variety of cardiac pathology including myocardial fibrosis, inflammation and necrosis plus calcification, edema and focal hemorrhage. Arterial pathology includes elastic degeneration, fibrosis, hyalinization and necrosis. This pathology has been found with light and electron microscopy and has been reviewed along with some other trace elements implicated in human heart disease. Perhaps the myocardial infarctions associated with ambient particulate matter mentioned occur in people with impaired copper status. The low amount of copper frequently found in the Western diet may contribute to ischemic heart disease by a variety of mechanisms. Chemical analysis of organs from their animals and evaluation of known cardiovascular correlates of copper deficiency such as elastic degeneration or smooth muscle proliferation in arteries may be helpful in testing the hypothesis that the combustion particles induced copper deficiency in the animals. Plasma copper and ceruloplasmin are not likely to be useful because both increase in the acute phase response to inflammation. References Allen, K.G. and Klevay, L.M. (1978). Cholesterolemia and cardiovascular abnormalities in rats caused by copper deficiency. Atherosclerosis 29, 81-93. Klevay, L.M. (2000a). The illness and death of a female hyena poisoned by zinc ingested as pennies. J. Zoo Wildl. Med. 31, 289-290. Klevay, L.M. (2000b). Trace element and mineral nutrition in disease: Ischemic heart disease. In Clinical Nutrition of the Essential Trace Elements and Minerals: The Guide for Health Professionals (J.D. Bogden and L.M. Klevay, Eds.), pp. 251-271. Humana Press Inc., Totowa, NJ. Klevay, L.M., Pond, W.G., and Medeiros, D.M. (1994). Decreased high density lipoprotein cholesterol and apoprotein A-I in plasma and ultrastructural pathology in cardiac muscle of young pigs fed a diet high in zinc. Nutr. Res. 14, 1227-1239. Kodavanti, U.P., Moyer, C.F., Ledbetter, A.D., Schladweiler, M.C., Costa, D.L., Hauser, R., Christiani, D.C., and Nyska, A. (2003). Inhaled environmental combustion particles cause myocardial injury in the Wistar Kyoto rat. Toxicol. Sci. 71, 237-245. Kopp, S.J., Klevay, L.M., and Feliksik, J.M. (1983). Physiological and metabolic characterization of a cardiomyopathy induced by chronic copper deficiency. Am. J. Physiol. 245, H855-H866.

Technical Abstract: Kodavanti et al. induced cardiomyopathy in Wistar Kyoto rats by inhalation exposure to environmental combustion particles similar to ambient particulate matter and rich in bioavailable zinc. Myocardial degeneration, inflammation and fibrosis were prominent. No direct, mechanistic data were available. The only mechanism known by which zinc intoxication produces pathology is by the induction of copper deficiency. This antagonism has been known for nearly 60 years; some of the numerous animal species victimized have been reviewed. Copper deficiency, whether induced by a diet low in copper or by excess zinc, induces a wide variety of cardiac pathology including myocardial fibrosis, inflammation and necrosis plus calcification, edema and focal hemorrhage. Arterial pathology includes elastic degeneration, fibrosis, hyalinization and necrosis. This pathology has been found with light and electron microscopy and has been reviewed along with some other trace elements implicated in human heart disease. Perhaps the myocardial infarctions associated with ambient particulate matter mentioned occur in people with impaired copper status. The low amount of copper frequently found in the Western diet may contribute to ischemic heart disease by a variety of mechanisms. Chemical analysis of organs from their animals and evaluation of known cardiovascular correlates of copper deficiency such as elastic degeneration or smooth muscle proliferation in arteries may be helpful in testing the hypothesis that the combustion particles induced copper deficiency in the animals. Plasma copper and ceruloplasmin are not likely to be useful because both increase in the acute phase response to inflammation. References Allen, K.G. and Klevay, L.M. (1978). Cholesterolemia and cardiovascular abnormalities in rats caused by copper deficiency. Atherosclerosis 29, 81-93. Klevay, L.M. (2000a). The illness and death of a female hyena poisoned by zinc ingested as pennies. J. Zoo Wildl. Med. 31, 289-290. Klevay, L.M. (2000b). Trace element and mineral nutrition in disease: Ischemic heart disease. In Clinical Nutrition of the Essential Trace Elements and Minerals: The Guide for Health Professionals (J.D. Bogden and L.M. Klevay, Eds.), pp. 251-271. Humana Press Inc., Totowa, NJ. Klevay, L.M., Pond, W.G., and Medeiros, D.M. (1994). Decreased high density lipoprotein cholesterol and apoprotein A-I in plasma and ultrastructural pathology in cardiac muscle of young pigs fed a diet high in zinc. Nutr. Res. 14, 1227-1239. Kodavanti, U.P., Moyer, C.F., Ledbetter, A.D., Schladweiler, M.C., Costa, D.L., Hauser, R., Christiani, D.C., and Nyska, A. (2003). Inhaled environmental combustion particles cause myocardial injury in the Wistar Kyoto rat. Toxicol. Sci. 71, 237-245. Kopp, S.J., Klevay, L.M., and Feliksik, J.M. (1983). Physiological and metabolic characterization of a cardiomyopathy induced by chronic copper deficiency. Am. J. Physiol. 245, H855-H866.