Cytopathology

Biography

Biography: Ivo JURANEK

Abstract

Free (oxygen) radicals, produced in increased concentration during cellular damage, are generally considered as a cause of such damage. This substantiated theory of free-radical diseases when uncontrolled overproduction of reactive oxygen species (ROS), termed oxidative stress, leads to oxidative alteration of integral cellular components and important macromolecules, like lipids, proteins and nucleic acids, which readily results in cellular damage. Subsequently, cells may undergo death, which if occurring in a massive scale is manifested as tissue damage, which in turn often leads to organ dysfunction. That is why, substances with antioxidative properties were supposed to act as efficient agents towards free-radical diseases. However, a number of large-scale clinical trials have demonstrated that administration of exogenous antioxidants failed to be effective, and often led to serious complications. E.g., CARET study, involving 18,000 smokers and beta-carotene, reported significantly higher lung cancer incidence (by ~30%) as well as mortality rate due to lung cancer (by ~20%) in comparison to placebo group. The present paper covers negative findings from several unsuccessful clinical trials and provides a possible explanation of the phenomenon. Undesirable effects of antioxidants are likely due to their unfavorable action onto the fundamental ROS-mediated physiologic processes, such as oxidative phosphorylation, removal of defective and cancer cells, intra- and inter-cellular signaling. Concluding, use of exogenous antioxidants aiming to treat pathologies involving oxidative damage either in therapeutic or preventive/prophylactic mode has to be thoroughly weighed up. Acknowledgement: The paper was partly supported by the Slovak Agency VEGA (2/0149/12)