Reactive oxygen and nitrogen species generation features under conditions of acute hepatotoxicity


  • I. О. Shmarakov Y. Fedkovych Chernivtsi National University
  • V. L. Borschovetska Y. Fedkovych Chernivtsi National University
  • М. М. Marchenko Y. Fedkovych Chernivtsi National University
Keywords: hepatotoxicity, superoxide, nitric oxide, vitamin A

Abstract

Development of the most of pathological conditions occurs by free radical mechanism which is characterized by increased free radical production at the cellular level, especially reactive oxygen and nitrogen species (ROS/RNS). The main producers of reactive oxygen species are, first of all, membrane bound NADH-dependent mitochondrial and NADPH-dependent endoplasmic reticulum electron transport systems, cytosolic oxidoreductase enzymes and multienzyme complexes. The aim of the study was to determine the features of generation of superoxide anion radical (O2·) as the primary reactive oxygen species, and nitric oxide (NO·) under conditions of thioacetamide-induced hepatotoxicity. The features of NAD(P)H-dependent gen-eration of superoxide anion radical (O2·) as the primary reactive oxygen species, and nitric oxide (NO·) in subcellular (mitochondrial, microsomal and post-microsomal) fractions of C57BL/6J mouse liver cells isolated by the method of differential centrifugation were determined under conditions of thioacetamide-induced hepatotoxicity and supplementation with pharma-cological doses of vitamin A. It was found that the development of acute hepatotoxicity induced by single intraperitoneal ad-ministration of 500 mg/kg of thioacetamide was accompanied by increased intensity of superoxide anion radical and nitric oxide production in microsomal and cytosolic fractions of liver cells, but not in mitochondrial fraction. Consumption of the pharmacological doses of vitamin A (3000 IU) has no hepatoprotective effect, however, it enhances the production of reactive oxygen and nitrogen species in the liver during acute hepatotoxicity. 

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Published
2014-02-21
Section
Articles