ABSTRACT
The liver is damaged by sustained ischaemia during liver transplantation, and the reperfusion after ischaemia results in further functional impairment. Ozone oxidative preconditioning (OzoneOP) protected the liver against ischaemia/reperfusion (I/R) injury through different mechanisms. The aim of this study was to investigate the influence of the inhibition of protein synthesis on the protective actions conferred by OzoneOP in hepatic I/R. Rats were treated with cycloheximide (CHX) in order to promote protein synthesis inhibition after OzoneOP treatment. Plasma transaminases, malondialdehyde and 4-hydroxyalkenals and morphological characteristics were measured as an index of hepatocellular damage; Cu/Zn-superoxide dismutase (SOD), Mn-SOD, catalase, total hydroperoxides and glutathione levels as markers of endogenous antioxidant system. OzoneOP increased Mn-SOD isoform and ameliorated mitochondrial damage. CHX abrogated the protection conferred by OzonoOP and decreased Mn-SOD activity. Cellular redox balance disappeared when CHX was introduced. Protein synthesis is involved in the protective mechanisms mediated by OzoneOP. Ozone treatment preserved mitochondrial functions and cellular redox balance.
Subject(s)
Liver Transplantation , Liver/injuries , Liver/metabolism , Ozone/administration & dosage , Protein Biosynthesis , Alanine Transaminase/blood , Animals , Aspartate Aminotransferases/blood , Catalase/metabolism , Cycloheximide/pharmacology , Glutathione/metabolism , Glutathione Disulfide/metabolism , Ischemic Preconditioning , Liver/drug effects , Liver/ultrastructure , Liver Transplantation/adverse effects , Liver Transplantation/physiology , Male , Microscopy, Electron , Oxidation-Reduction , Protein Synthesis Inhibitors/pharmacology , Rats , Rats, Wistar , Superoxide Dismutase/metabolismABSTRACT
The reactive oxygen species (ROS) can damage the nucleic acids. The oxidative modification of the DNA constitutes the fundamental molecular event in carcinogenesis and that is why the interest in the study of the involvement of ROS in that process. On the other hand, oxidative DNA damage-induced mutagenesis is widely hypothesized to be a frequent event in the normal human cell. The enormous evidence suggests an important role of ROS in the expansion and progression of tumor clones, being considered a relevant class of carcinogens. In addition, the use of immunohistochemical techniques has showed that the various types of cancer examined to date manifest an imbalance in their antioxidant mechanisms to respect the primary cell. In the near future new insights in cancer therapies, based on modulation of cellular redox status, may lead the way to additional tools against carcinogenesis from ROS.
