Beneficial effects of trimetazidine on mitochondrial function and superoxide production in the cardiac muscle of monocrotaline-treated rats.
The administration of a single dose of monocrotaline (105 mg/kg) after 21 days produced in rats a reduction of cardiac mitochondrial function at the level of complexes I, II and IV of the respiratory chain, associated with the formation of heart hypertrophy, prevalently of the right ventricle. Moreover, in these rats, the submitochondrial particles produced more O2- and in the cardiac tissue there was an elevation of malondialdehyde content. The repeated administration of trimetazidine (5 mg/kg/24 hr) improved the cardiac mitochondrial function, particularly in state 3 of respiration. In addition, the treatment with trimetazidine reduced, in the heart muscle, both the production of mitochondrial O2- and the content of tissue malondialdehyde. Trimetazidine added alone did not significantly change either the cardiac mitochondrial activity, or the mitochondrial O2- production in comparison to control rats. Also, the content of tissue malondialdehyde was not modified by the repeated administration of trimetazidine. In all the experimental conditions examined, the content of cardiac water-soluble fluorescence substrates did not significantly change in comparison to control rats.
Guarnieri
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Department of Biochemistry, University of Bologna, Italy.
Muscari
C
C
D000818:Animals; D006332:Cardiomegaly / Q000139:chemically induced*; D004579:Electron Transport / Q000187:drug effects; D008054:Lipid Peroxides / Q000378:metabolism; D008297:Male; D008929:Mitochondria, Heart / Q000187:drug effects*; D016686:Monocrotaline; D010085:Oxidative Phosphorylation / Q000187:drug effects; D010101:Oxygen Consumption / Q000187:drug effects; D010879:Piperazines / Q000494:pharmacology*; D011763:Pyrrolizidine Alkaloids / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013481:Superoxides / Q000096:biosynthesis*; D014292:Trimetazidine / Q000494:pharmacology*
D008054:Lipid Peroxides; D010879:Piperazines; D011763:Pyrrolizidine Alkaloids; D013481:Superoxides; D016686:Monocrotaline; D014292:Trimetazidine