Abstract

Free radical reactions play an important role in biological functions of living systems. The balance between oxidants and antioxidants is necessary for the normal homeostasis of cells and organisms. Experimental works demonstrate the role of oxidative stress that is caused by influenza virus as well as the toxic effects of some antiviral drugs. Therefore, antiviral drugs should be characterized by its pro- and antioxidant activity, because it can affect its therapeutic efficiency. The aim of the study was to quantify the antioxidant capacity and propose the mechanism of the antioxidant effect of the antiviral drug Umifenovir (Arbidol®). The kinetic chemiluminescence with the 2,2’-azobis (2-amidinopropane) dihydrochloride + luminol system was used to quantify the antioxidant capacity of Umifenovir relative to the standard compound Trolox. With computer simulation, the reaction scheme and rate constants were proposed. The antioxidant capacity of 0.9 μM Umifenovir (maximum concentration of Umifenovir in blood after oral administration of 200 mg) was as high as 1.65 ± 0.18 μM of Trolox. Thus, the total antioxidant capacity of Umifenovir is comparable to the antioxidant capacity of Trolox. Unlike Trolox, Umifenovir reacts with free radicals in two stages. For Trolox, the free radical scavenging rate constant was k = 2000 nM−1 min.−1, for Umifenovir k1 = 300 nM−1min.−1, k2 = 4 nM−1min.−1. Slower kinetics of Umifenovir provides the prolonged antioxidant effect when compared to Trolox. This phenomenon can make a serious contribution to the compensation of oxidative stress that is caused by a viral disease and the therapeutic effect of the drug.

Highlights

  • Free radical reactions play an important role in the biological functions of living systems.The balance between prooxidants and antioxidants is necessary for the normal homeostasis of cells and organisms

  • The Antioxidant Capacity of Umifenovir Assessed by Modified TRAP Method

  • The steady-state production of free radicals was provided by the decomposition of 2,20 -azobis

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Summary

Introduction

Free radical reactions play an important role in the biological functions of living systems. The balance between prooxidants and antioxidants is necessary for the normal homeostasis of cells and organisms. Oxidative stress plays an important role in many pathological processes, including viral infections, such as influenza [1]. Excessive reactive oxygen species (ROS) cause oxidative damage of lipid membranes and mitochondrial respiratory chain. Mitochondria act as a platform for antiviral innate immunity. Mitochondrial antiviral signaling involves the activation of the retinoic acid-inducible gene I-like receptors, which requires oxidative phosphorylation activity. The cells with respiratory defects exhibited severely impaired virus-induced induction of interferons and proinflammatory cytokines. Mice with respiratory chain defects were highly susceptible to viral infection and exhibited significant lung inflammation [2]. Oxidative and nitrosative stress may contribute to reduced

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