Oxidative stress, a trigger of hepatitis C and B virus-induced liver carcinogenesis

Abstract

Virally induced liver cancer usually evolves over long periods of time in the context of a strongly oxidative microenvironment, characterized by chronic liver inflammation and regeneration processes. They ultimately lead to oncogenic mutations in many cellular signaling cascades that drive cell growth and proliferation. Oxidative stress, induced by hepatitis viruses, therefore is one of the factors that drives the neoplastic transformation process in the liver. This review summarizes current knowledge on oxidative stress and oxidative stress responses induced by human hepatitis B and C viruses. It focuses on the molecular mechanisms by which these viruses activate cellular enzymes/systems that generate or scavenge reactive oxygen species (ROS) and control cellular redox homeostasis. The impact of an altered cellular redox homeostasis on the initiation and establishment of chronic viral infection, as well as on the course and outcome of liver fibrosis and hepatocarcinogenesis will be discussed The review neither discusses reactive nitrogen species, although their metabolism is interferes with that of ROS, nor antioxidants as potential therapeutic remedies against viral infections, both subjects meriting an independent review.

Counteraction of HCV-Induced Oxidative Stress Concurs to Establish Chronic Infection in Liver Cell Cultures

“…Oxidative stress, an imbalance between the reactive oxygen species (ROS) production and their clearance by scavenging molecules, has been recognized as a leading factor in inducing hepatocyte death, inflammation, and fibrogenesis, which are responsible for induction and perpetuation of liver damage [5]. Several authors report a rise of ROS levels during HCV infection [6][7][8][9][10][11][12][13], and various viral proteins are known to induce and/or augment the ROS production, including HCV core, E1, E2, nonstructural (NS) 3, NS4B, and NS5A [11,[14][15][16][17]. Moreover, the simultaneous induction of several ROS-producing pathways and enzymes, such as the endoplasmic reticulum (ER) oxidoreductases [15,18] and NADPH (nicotinamide adenine dinucleotide phosphate) oxidases (NOXs) [15,16,19], also contributes to HCV-induced oxidative stress.…”

“…Moreover, the simultaneous induction of several ROS-producing pathways and enzymes, such as the endoplasmic reticulum (ER) oxidoreductases [15,18] and NADPH (nicotinamide adenine dinucleotide phosphate) oxidases (NOXs) [15,16,19], also contributes to HCV-induced oxidative stress. On the contrary, other studies report an increase in the antioxidant defenses, such as superoxide dismutase (SOD), peroxiredoxin (PRDX), glutathione S-transferase (GST) enzyme activity, and GSH levels [14,[20][21][22][23]. Glutathione is an important radical scavenger that directly and indirectly neutralizes a variety of reactive molecules, such as superoxide anions (O 2 ⋅− ), hydroxyl radicals, and hydrogen peroxide (H 2 O 2 ) [24].…”

Differential Proteomic Analysis of Dimethylnitrosamine (DMN)‐Induced Liver Fibrosis

“…Evidence supported that DMN is related to production of reactive oxygen species (ROS) that have been observed to injury liver, followed by the oxidation of lipids, proteins, and DNA . Oxidative stress is implicated in the development of liver fibrosis . The significantly increased MDA content and reduced SOD activity showed more severe oxidative stress and weakened resistance capability in the DMN model group.…”

Mitochondria in the biology, pathogenesis, and treatment of hepatitis virus infections

“…During cellular respiration, byproducts like ROS are produced under stressed conditions . Increased ROS production is associated with liver injury and the pathogenesis of viral hepatitis . Furthermore, ROS production is involved in various cellular signaling pathways, including those mediating immune responses.…”