Pharmacological Correction of the Negative Effect of Acetylsalicylic Acid on the Energy-Generating System

Olga S. Brushinina, PhD, Roman V. Gurto*, PhD, Galina A. Frelikh, Vladimir V. Udut, ScD

Federal State Budgetary Institution «Research Institute of Pharmacology», Siberian Branch of the RAMS, Tomsk, Russian Federation

*Corresponding author: Roman V. Gurto, PhD, Leading Researcher, Laboratory of Physiology, Molecular and Clinical Pharmacology, Federal State Budgetary Institution «Research Institute of Pharmacology», Siberian Branch of the Russian Academy of Medical Sciences, 3, Lenin ave., 634028, Tomsk, Russian Federation. Tel/Fax: 7-3822-418373 E-Mail:roman.gurto@gmail.com

Abstract: 

The present paper demonstrates the effect of acetylsalicylic acid (ASA) and its combination with succinic acid (SUC) on the energy-producing system of rat heart mitochondria as well as an assessment of SUC preventive application effect on ASA pharmacokinetic parameters. Experiments conducted on outbred male albino rats (200-250 g) on a model of a xenobiotic load induced by seven days of intragastric injections of acetylsalicylic acid at a dose of 250 mg/kg have shown inhibition of the oxygen consumption rates in the heart mitochondria as well as a limitation of the succinate-dependent substrate oxidation pathways and a decrease in the mitochondria ATP/ADP coefficient. Succinic acid (50 mg/kg for 7 days) was injected as a preventive medication to correct the mitochondrial bioenergetics revealed. A comparative research of the pharmacokinetics of acetylsalicylic acid and acetylsalicylic acid against the background of succinic acid performed on the model of rabbits has shown total similarity in the parameters analyzed. This fact demonstrates the possibility of prevention of mitochondrial dysfunction using the intermediate Krebs cycle. SUC as preventive medication promotes the elimination of ASA-induced negative metabolic shifts in the rat heart mitochondria by normalizing the succinate- and NAD-dependent respiration, oxidative phosphorylation, and therefore, it finds good use in the correction of ASA-induced negative side-effects of an energy-generating system.

Keywords: 
acetylsalicylic acid; mitochondria; pharmacokinetics; bioenergetics; succinic acid.
References: 

1. Vertkin AL, Aristarkhova OJu, Adonina EV, et al. Safety and pharmacological efficiency of using various acetylsalicylic acid drugs in patients with IHD.  Rus Med J 2009; 17(8).
2. Karpov Ju A. Acetylsalicylic acid is a key position in primary and secondary prevention of cardiovascular diseases and their complications.  Rus Med J 2008; 16(11).
3. Oganov RJ, Maslennikova JJa. Cardiovascular diseases in the Russian Federation in the second half of XXth century: trends, possible reasons, prospects. Cardiol 2000; 6: 4-8.
4. Bulatnikov AP. The effect of ammonium succinate on the main pharmacological properties of acetylsalicylic acid. PhD thesis.Tomsk, 1999.
5. Gutknecht J. Aspirin, acetaminophen and proton transport through phospholipid bilayers and mitochondrial membranes. Mol Cell Biochem 1992; 114 (1): 3–8.
6. Jolliet P, Widmann J. Reye's syndrome in adult with AIDS. Lancet 1990; 335 (8703):1457.
7. Vengerovsky AI, Khazanov VA., Timofeev MS, Slepichev VA, Ivanov VV. The effect of hepatoprotectors and energy metabolism regulator on the functional state of liver mitochondria in experimental Reye’s syndrome. Bulletin of experimental biology and medicine 2003; Supplement 2: 89-91.
8. Vasiljev KJu. Age pecularities of energy-protector effect of mitochondrial substrates under complex influence of stress and intoxication. PhD thesis. Tomsk, 2005.
9. Smirnova NB, Khazanov VA. Correction of pathologic states in the experiment using energy metabolism regulators. In: Khazanov VA, editor. Energy metabolism regulators. Clin. Pharmac. Aspects, 2004. p 109-113.
10. Kondrashova MN, Ananenko AA. Examination of isolated mitochondria state. In: Manual on studying biological oxidation using polarographic method.  Moscow, 1973. p 106-129.
11. Kondrashova M N. Interaction of processes of pereamination in various functional tissue states. Biochem 1991; 53 (3):388-402.
12. Khazanov VA. Pharmacology and pharmacoeconomics of a new class of drugs-energy metabolism regulators. In: Khazanov VA, editor. Energy metabolism regulators. 2003. p 13-14.
13. Khazanov VA. Past, present and future of bioenergetic pharmacology. In: Khazanov VA, editor. Energy metabolism regulators. Clin. Pharmac. Aspects, 2004. p 3-7.

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Int J Biomed. 2012; 2(1):58-61. © 2012 International Medical Research and Development Corporation. All rights reserved.