Redox control of liver function in health and disease.
Reactive oxygen species (ROS), a heterogeneous population of biologically active intermediates, are generated as by-products of the aerobic metabolism and exhibit a dual role in biology. When produced in controlled conditions and in limited quantities, ROS may function as signaling intermediates, contributing to critical cellular functions such as proliferation, differentiation, and cell survival. However, ROS overgeneration and, particularly, the formation of specific reactive species, inflicts cell death and tissue damage by targeting vital cellular components such as DNA, lipids, and proteins, thus arising as key players in disease pathogenesis. Given the predominant role of hepatocytes in biotransformation and metabolism of xenobiotics, ROS production constitutes an important burden in liver physiology and pathophysiology and hence in the progression of liver diseases. Despite the recognized role of ROS in disease pathogenesis, the efficacy of antioxidants as therapeutics has been limited. A better understanding of the mechanisms, nature, and location of ROS generation, as well as the optimization of cellular defense strategies, may pave the way for a brighter future for antioxidants and ROS scavengers in the therapy of liver diseases.
Liver Unit, Hospital Clinic, IDIBAPS-CIBEK, CIBEREHD, and Department of Cell Death and Proliferation, IIBB-CSIC, Barcelona, Spain.
Montserrat
M
Marí
Anna
A
Colell
Albert
A
Morales
Claudia
C
von Montfort
Carmen
C
Garcia-Ruiz
José C
JC
Fernández-Checa
D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use; D016166:Free Radical Scavengers / Q000627:therapeutic use; D006262:Health; D006801:Humans; D008099:Liver / Q000378:metabolism*; D008107:Liver Diseases / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D010084:Oxidation-Reduction; D017382:Reactive Oxygen Species / Q000378:metabolism
D000975:Antioxidants; D016166:Free Radical Scavengers; D017382:Reactive Oxygen Species