USDA, P.O. Box 9034, University Station Grand Forks, ND 58202 Lklevay{at}gfhnrc.ars.usda.gov
To the Editor:
Kodavanti et al.(2003) 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 (Klevay, 2000a).
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, as well as calcification, edema, and focal hemorrhage. Arterial pathology includes elastic degeneration, fibrosis, hyalinization, and necrosis. This pathology has been found with light (Allen and Klevay, 1978) and electron microscopy (Klevay et al., 1994
; Kopp et al., 1983
) and has been reviewed along with some other trace elements implicated in human heart disease (Klevay, 2000b
).
Perhaps the myocardial infarctions associated with ambient particulate matter mentioned (Kodavanti et al., 2003) occur in people with marginal intakes of copper whose nutritional status is impaired further by airborne zinc. The low amount of copper frequently found in the Western diet may contribute to ischemic heart disease by a variety of mechanisms (Klevay, 2000b
).
Perhaps the authors (Kodavanti et al., 2003) will test the hypothesis that combustion particles induce copper deficiency in animals by measuring copper in organs and by examining arteries for known cardiovascular correlates of copper deficiency such as elastic degeneration or smooth muscle proliferation or by repeating the experiment with added dietary copper to determine whether or not the effects can be decreased or prevented. This latter method has been used (Lamb et al., 2002
) to mitigate adverse effects of classic atherogenic diets. Plasma copper and ceruloplasmin are not likely to be useful because both increase in the acute phase response to inflammation.
Two apparently dissimilar determinants of myocardial infarctionair pollution and dietmay involve decreased copper utilization.
REFERENCES
Allen, K. G., and Klevay, L. M. (1978). Cholesterolemia and cardiovascular abnormalities in rats caused by copper deficiency. Atherosclerosis 29, 8193.[ISI][Medline]
Klevay, L. M. (2000a). The illness and death of a female hyena poisoned by zinc ingested as pennies. J. Zoo Wildl. Med. 31, 289290.[ISI][Medline]
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. 251271. Humana Press, 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, 12271239.[ISI]
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, 237245.
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, H855H866.[ISI][Medline]
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