Pharmacological correction of the negative effects of acetylsalicylic acid on the energy production system.
Experiments of outbred rats with modeled xenobiotic load with acetylsalicylic acid (250 mg/kg for 7 days) revealed inhibition of mitochondrial respiration rate in states of rest and active phosphorylation, inhibition of succinate-dependent oxidation pathway, and a decrease in energization of organelles in the heart. For correction of the observed changes in energy production, succinic acid was preventively administered in a dose of 50 mg/kg for 7 days, which abolished the negative metabolic shifts in myocardial mitochondria. Comparison of pharmacokinetics of acetylsalicylic acid and acetylsalicylic acid against the background of succinate treatment performed on rabbits revealed complete coincidence of the studied parameters, which attests to the possibility of prevention of mitochondrial dysregulations with this Krebs cycle intermediate.
Laboratory of Physiology, Molecular and Clinical Pharmacology, Department of Clinical Pharmacology, Institute of Pharmacology, Siberian Division of the Russian Academy of Medical Sciences, Tomsk, Russia.
O S
OS
Bryushinina
R V
RV
Gurto
V A
VA
Slepichev
G A
GA
Stykon
Yu G
YG
Zyuz'kova
E A
EA
Yanovskaya
V V
VV
Udut
D000818:Animals; D019540:Area Under Curve; D001241:Aspirin / Q000493:pharmacokinetics / Q000494:pharmacology*; D019069:Cell Respiration / Q000187:drug effects*; D004734:Energy Metabolism / Q000187:drug effects* / Q000502:physiology; D006321:Heart / Q000502:physiology*; D008928:Mitochondria / Q000187:drug effects*; D011048:Polarography; D011817:Rabbits; D051381:Rats; D019802:Succinic Acid / Q000494:pharmacology*
D019802:Succinic Acid; D001241:Aspirin