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PP-028 Investigation of the new metabolic cardiotonic drug sufan
  1. I Nizhenkovskaya
  1. A. A. Bogomolets National Medical University of Ministry of Health of Ukraine ww, Pharmaceutical, Kiev, Ukraine

Abstract

Background Adverse drug reactions are a major problem of modern pharmacotherapy. Many drugs’ side effects narrow their field of use; require special medical care and careful checks when they are used. One of such drugs is an antitumor antibiotic adriamycin, which causes the development of cardiomyopathy that manifests itself first of all by causing heart failure in patients. The adriamycin-induced intoxication is also accompanied by severe disturbances of many heart muscle cell enzyme systems. The administration of cardiac glycosides in the event of adriamycin-induced intoxication does not reduce its severity, but rather increases the structural abnormalities in the myocardium.

Purpose To explore the possibilities of correcting energy metabolism and oxidative homeostasis disorders in the myocardium of rats, which were given sufan during adriamycin-induced intoxication.

Materials and methods The investigations were conducted on 120 Wistar male rats, weighing 150–200 g. These animals were divided into 4 groups: 1st – the control group; 2nd – animals that were injected only with sufan (35 mg/kg); 3rd group – animals that were injected only with anthracycline antibiotic; 4th group – animals that were injected with adriamycin in combination with sufan. Adriamycin was administered intramuscularly once a week (5 mg/kg) for 5 weeks; sufan was administered daily intramuscularly (IM) for 5 weeks. The rats’ myocardial tissue, brain and spleen were studied. 10% homogenates were prepared in 0.05 M Tris buffer (pH 7.4). All manipulations were carried out at a temperature + 4°C. In myocardial tissue the content of nicotinamide coenzymes (nicotinamide adenine dinucleotide oxidised form (NAD+) and the reduced form (NADH), nicotinamide adenine dinucleotide phosphate oxidised form (NADP+) and the reduced form (NADPH) was determined with the use of fluorometry; the activity of NAD-hydrolase by the enzymatic method; the content of creatine phosphate (CP) in the myocardial homogenate was determined as a difference between total and free creatine via spectrophotometry; the activity of the creatine phosphokinase (CPK) was assessed using the photo-colorimetric method; the adenine system components were determined with the help of spectrophotometry.

Results We determined that the IM administration of sufan in intact rats at a dose of 35 mg/kg daily for 5 weeks led to a 10.5% reduction in the reduced form of the nicotinamide coenzymes in the myocardium, which in turn increased the ratio of oxidised: reduced forms (+14.3%). This fact indicates a decrease in the degree of coenzyme reduction that can be regarded as a positive effect on the functioning of various chains of cell metabolism. In the same experimental conditions sufan showed little effect on the number of adenine system components and on the content of inorganic phosphate; it increased slightly the level of CP and glycogen in the myocardium. Anthracycline intoxication was induced experimentally in rats (by the IM administration of adriamycin at a dose of 5 mg/kg a week for 5 weeks). This intoxication was characterised by a deterioration in the energy metabolism in myocardial tissues (a decrease in oxidised forms and the total amount of nicotinamide coenzymes, CP, glycogen, ratio of oxidised: reduced forms, the amount of ATP and ADP and at the same time an increase in NAD-hydrolase activity and the ADP/ATP ratio and the amount of inorganic phosphate). It was also characterised by LPO [lipid peroxidation] activation in myocardial, brain and spleen tissues.

Conclusions The IM use of sufan at a dose of 35 mg/kg during adriamycin-induced intoxication reduced the severity of energy metabolism and oxidative homeostasis disorders in myocardium, brain and spleen.

No conflict of interest.

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