Influence of lipopolysaccharide on the development of oxidative-nitrosative stress in the liver of rats under conditions of chronic alcohol intoxication

Abstract

Alcohol abuse is a common phenomenon among the countries of the European continent. One of the first organs suffering from alcohol-induced damage is the liver. Activation of Kupffer cells, as part of the mononuclear phagocyte system, plays a significant role in the development of oxidative-nitrosative damage of the liver. Systemic inflammatory response affects the polarization of macrophages throughout the body and may affect the development of alcohol damage of hepatocytes. The aim of this work is to study the effect of in vivo stimulation by S. typhi bacterial lipopolysaccharide on the development of oxidative-nitrosative stress in rat liver under conditions of chronic alcohol intoxication. Male Wistar rats were randomly divided into 4 groups: I - control; II - rats received 0.4 μg/kg of bacterial lipopolysaccharide of S. typhi; III - rats with induced alcoholic hepatitis, and IV - rats with chronic alcohol intoxication and injected bacterial lipopolysaccharide. The experiment lasted 63 days. We studied pro-oxidants antioxidant enzymes, the concentration of sulfide anion, nitric oxide production and malonic dialdehyde concentration in liver tissues. In vivo administration of bacterial lipopolysaccharide enhances ethanol-induced oxidative liver damage via increased production of superoxide anion despite the adaptive increase in the activity of antioxidant enzymes. Nitric oxide, the production of which increases in the liver during prolonged stimulation of the rat body with bacterial lipopolysaccharide, chronic alcohol intoxication and their combination, mainly metabolizes to peroxynitrite