Abstract
The exogenous lipoic acid (LA) is successfully used as a drug in the treatment of many diseases. It is assumed that after administration, LA is transported to the intracellular compartments and reduced to dihydrolipoic acid (DHLA) which is catalyzed by NAD(P)H-dependent enzymes. The purpose of this study was to investigate whether LA can attenuate cardiovascular disturbances induced by ethanol (EtOH) and disulfiram (DSF) administration separately or jointly in rats. For this purpose, we measured systolic and diastolic blood pressure, recorded electrocardiogram (ECG), and estimated mortality of rats. We also studied the activity of aldehyde dehydrogenase (ALDH) in the rat liver. It was shown for the first time that LA partially attenuated the cardiac arrhythmia (extrasystoles and atrioventricular blocks) induced by EtOH and reduced the EtOH-induced mortality of animals, which suggests that LA may have a potential for use in cardiac disturbance in conditions of acute EtOH intoxication. The administration of EtOH, LA, and DSF separately or jointly affected the ALDH activity in the rat liver since a significant decrease in the activity of the enzyme was observed in all treatment groups. The results indicating that LA is an inhibitor of ALDH activity are very surprising.
Highlights
According to the World Health Organization (WHO) in 2016, the alcohol abuse resulted in 3 million deaths (5.3% of all deaths) worldwide and 132.6 million disabilityadjusted life years (DALYs), i.e., 5.1% of all DALYs in that year [1]
EtOH can be oxidized to acetaldehyde by three routes: (1) in the presence of NAD in the reversible reaction catalyzed by alcohol dehydrogenase (ADH; E.C 1.1.1.1), (2) in the presence of NADPH and molecular oxygen (O2) in the reaction catalyzed by microsomal ethanol oxidizing system (MEOS), and (3) in the presence of hydrogen peroxide (H2O2) in the reaction catalyzed by catalase
Prancheva et al described a case of a 53-yearold man in whom DSF-EtOH reaction (DER) manifested as severe hypotension accompanied by ischemic stroke [13]
Summary
According to the World Health Organization (WHO) in 2016, the alcohol abuse resulted in 3 million deaths (5.3% of all deaths) worldwide and 132.6 million disabilityadjusted life years (DALYs), i.e., 5.1% of all DALYs in that year [1]. DALYs are the sum of years of life lost due to premature mortality as well as years of life lost due to time lived in less than full health. According to the authors of that report, the cardiovascular diseases (CVDs) are the leading cause of mortality globally, causing 17.9 million deaths (31.6% of all deaths) and 413.2 million DALYs (15.9% of all DALYs). Metabolism of ethanol (EtOH) in the human body occurs mainly in the liver. EtOH can be oxidized to acetaldehyde by three routes: (1) in the presence of NAD in the reversible reaction catalyzed by alcohol dehydrogenase (ADH; E.C 1.1.1.1), (2) in the presence of NADPH and molecular oxygen (O2) in the reaction catalyzed by microsomal ethanol oxidizing system (MEOS), and (3) in the presence of hydrogen peroxide (H2O2) in the reaction catalyzed by catalase
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