Oxidative Stress: Cause and Consequence of Diseases

Oxidative stress, termed as an imbalance between production and elimination of reactive oxygen species (ROS) leading to plural oxidative modifications of basic and regulatory processes, can be caused in different ways. Increased steady-state ROS levels can be promoted by drug metabolism, overexpression of ROS-producing enzymes, or ionizing radiation, as well as due to deficiency of antioxidant enzymes. The plethora of ways leading eventually to oxidative stress is depicted in Figure 1. This chapter has several aims. The main aim is to show examples which mirror our knowledge on the role of oxidative stress in origin of diseases as well as its significance in disease complications. It was it that oxidative stress is described over developed pathology and nothing is told, if it was initial, triggering event or it was a consequence of the metabolic shift caused by other factors. Virtually, it would be important to develop a cure for specific diseases. The other aim of this chapter is to spotlight the role of enzyme deficiencies in promotion of oxidative stress during pathological conditions. These deficiencies are often caused by mutations in genes coding antioxidant or related enzymes, i.e. by genetic polymorphism. Mutations are preconditions for many diseases, which cannot be prevented in most cases. Nevertheless, complete understanding of the ways from the gene to disease symptoms is necessary condition for successful therapy. Attention should be paid also to full or partial loss of the enzyme activity via exogenous factors or via other indirect reasons. Many connections can be drawn between certain pathologies and oxidative modification of proteins. Most antioxidant and related enzymes are targets for oxidative modification. Hence, if oxidative stress was primary event, possible oxidative modifications of antioxidant enzymes may exacerbate diseases and define cell destiny. Finally, it is worth mentioning advantages and disadvantages of diverse models which serve for disclosing of mechanisms underlying ROS contribution to diseases. Predominant number of studies is conducted on mice and cell cultures. Significant insights were received with use of lower organisms like budding yeast, nematodes and fruit flies. All model organisms and cell cultures have certain limitations and disadvantages. So far, the largest benefit can be brought out from complex studies, involving many model systems and investigating phenomena from different points of view.