Does the Interdependence between Oxidative Stress and Inflammation Explain the Antioxidant Paradox?

Abstract

Oxidative stress has been implicated in many chronic diseases. However, antioxidant trials are so far largely unsuccessful as a preventive or curative measure. Chronic low-grade inflammatory process, on the other hand, plays a central role in the pathogenesis of a number of chronic diseases. Oxidative stress and inflammation are closely related pathophysiological processes, one of which can be easily induced by another. Thus, both processes are simultaneously found in many pathological conditions. Therefore, the failure of antioxidant trials might result from failure to select appropriate agents that specifically target both inflammation and oxidative stress or failure to use both antioxidants and anti-inflammatory agents simultaneously or use of nonselective agents that block some of the oxidative and/or inflammatory pathways but exaggerate the others. To examine whether the interdependence between oxidative stress and inflammation can explain the antioxidant paradox we discussed in the present review the basic aspects of oxidative stress and inflammation and their relationship and dependence.

Figure 1

Major prooxidant-antioxidant reactions relevant in biological system. Superoxide (O₂ ^•−) produced from a number of sources acts as a primary reactive species. O₂ ^•− rapidly reacts with nitric oxide (NO^•) to produce peroxynitrite (ONOO⁻) or is catalyzed by superoxide dismutase (SOD) to produce hydrogen peroxide (H₂O₂). H₂O₂ can be neutralized by catalase or glutathione peroxidase. However, in presence of transition metal ions, like iron (Fe²⁺) and copper (Cu⁺), highly toxic hydroxyl free radicals (OH^•) can be produced from H₂O₂ via the Fenton reaction. Reactive species are shown in red and antioxidant enzymes are shown in green boxes. GSH, reduced glutathione; GS-SG, oxidized glutathione.

Figure 2

Overview of interdependence between oxidative stress and inflammation. When oxidative stress appears as a primary disorder inflammation develops as a secondary disorder and further enhances oxidative stress. On the other hand, inflammation as a primary disorder can induce oxidative stress as a secondary disorder which can further enhance inflammation. NF-κB, nuclear factor-κB; ROS, reactive oxygen species.