The effect of cobalt on mitochondrial ATP-production in the rat myocardium and skeletal muscle.
Cobalt has been shown to accumulate in the myocardium of uraemic patients and has been suggested as a myocardial toxin inhibiting mitochondrial respiration. In order to study the cellular effects of cobalt exposure three groups of rats (n = 12 per group) were fed a diet containing 12% protein without supplementation or with 20 mg and 40 mg CoSO4 7 H2O/kg body weight/day respectively. After 8 weeks the hearts and soleus muscles were removed. Cobalt in tissues and in four cell fractions were analysed with neutron-activation analysis (ng/g wet weight and ng/mg protein respectively). Mitochondrial respiration was analysed as ATP-production rate using pyruvate + malate and palmitoyl-carnitine + malate as substrate. The ATP-production from pyruvate + malate was unchanged in both heart and skeletal muscle in the exposed animals. With palmitate as substrate, the heart muscle showed a slightly lower ATP-production rate (p less than 0.05) after the 20 mg cobalt dose, but the rate was unchanged in the group with higher cobalt intake. No changes in ATP-production rate from palmitate was observed in soleus muscle. The microsomal (100,000 g) fraction in the myocardial cells contained significantly higher cobalt concentrations compared to the mitochondrial fraction in both the unexposed (1.4 ng/mg protein vs 0.19, p less than 0.05) and exposed rats (53.4 ng/mg protein vs 13.2, p less than 0.005). In conclusion, cobalt showed a large accumulation in myocardial cells, without significant effects on mitochondrial ATP-formation rate from oxidation of pyruvate or palmitate and with the highest cobalt content contained in the microsomal (100,000 g) fraction.
Clyne
N
N
Department of Medicine, Karolinska Hospital, Stockholm, Sweden.
Wibom
R
R
Havu
N
N
Hultman
E
E
Lins
L E
LE
Pehrsson
S K
SK
Persson
B
B
Rydström
J
J
D000255:Adenosine Triphosphate / Q000096:biosynthesis*; D000818:Animals; D003035:Cobalt / Q000378:metabolism / Q000494:pharmacology*; D007700:Kinetics; D008293:Malates / Q000378:metabolism; D008297:Male; D008861:Microsomes / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D008929:Mitochondria, Heart / Q000187:drug effects / Q000378:metabolism*; D009132:Muscles / Q000648:ultrastructure*; D010172:Palmitoylcarnitine / Q000378:metabolism; D011773:Pyruvates / Q000378:metabolism; D019289:Pyruvic Acid; D051381:Rats; D011919:Rats, Inbred Strains
D008293:Malates; D011773:Pyruvates; D010172:Palmitoylcarnitine; D003035:Cobalt; C030298:malic acid; D019289:Pyruvic Acid; D000255:Adenosine Triphosphate