Chronic cobalt exposure affects antioxidants and ATP production in rat myocardium.
Chronic cobalt exposure is characterized by severe cardiac insufficiency. Since the mechanisms of cobalt toxicity are not yet clear, we analysed the effects of chronic cobalt exposure on antioxidant enzyme activities and myocardial mitochondrial ATP production rate in a rat model. One group of rats was fed a conventional diet and another a cobalt supplemented diet for 24 weeks. The manganese-superoxide dismutase activity was markedly reduced in the cobalt rats (18+/-4.7 U/mg protein) compared to the control rats (100+/-22 U/mg protein; p <0.001). Activity in the respiratory chain enzymes succinate-cytochrome c reductase, NADH-cytochrome c reductase and cytochrome c oxidase was also reduced in the cobalt rats (p<0.01). Glutamate dehydrogenase activity, located in the mitochondrial matrix, was unchanged. The mitochondrial ATP production rate in relation to myocardial mass was lower in the cobalt rats for all substrates tested except palmitoyl-l-carnitine + malate. In conclusion, 24 weeks of chronic cobalt exposure induces a marked decrease in manganese-superoxide dismutase activity, a moderate decrease in mitochondrial ATP production rate and a general reduction in the capacity of the respiratory chain. The impairment in mitochondrial ATP production might be secondary to the decreased manganese-superoxide dismutase activity, causing inactivation of mitochondrial factors susceptible to superoxide radicals.
Clyne
N
N
Department of Nephrology, Karolinska Hospital, Stockholm, Sweden. Naomi.Clyne@medks.ki.se
Hofman-Bang
C
C
Haga
Y
Y
Hatori
N
N
Marklund
S L
SL
Pehrsson
S K
SK
Wibom
R
R
D000255:Adenosine Triphosphate / Q000096:biosynthesis*; D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D001835:Body Weight / Q000187:drug effects; D009202:Cardiomyopathies / Q000139:chemically induced / Q000378:metabolism; D003035:Cobalt / Q000633:toxicity*; D004579:Electron Transport / Q000187:drug effects; D006321:Heart / Q000187:drug effects*; D008297:Male; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism
D000975:Antioxidants; D013481:Superoxides; D003035:Cobalt; D000255:Adenosine Triphosphate; D013482:Superoxide Dismutase