Red blood cell oxidative stress and its ramifications’

All aerobic organisms use oxygen for their respiration and reduce it to water by stepwise adding electrons. Thus it is inevitable that these steps produce various oxygen radicals or reactive oxygen species (ROS) like superoxide, peroxide and hydroxyl radicals that can act as oxidants invivo. Accordingly, all living cells using oxygen have evolved to deal with these oxidants. If and when, these oxidants are in excess and not removed from the system, oxidative stress occurs.  In mammals, since red blood cells (RBCs) in particular, are the only cells carry oxygen to deliver to tissues, these cells are exposed to highest concentration of oxygen. In fact, RBCs have an extensive antioxidant system to eliminate the formation of ROS as soon as they are formed. Even then, an increase in RBC oxidative stress has been reported in many pathological conditions associated with various diseases and aging. Work from our laboratory has shown that under hypoxic conditions (such as when RBCs travel through micro-capillaries), the most predominant protein, hemoglobin in RBCs undergoes autoxidation producing superoxide and hydrogen peroxide and eventually breaks down itself to produce fluorescent heme degradation products that increase in different pathological conditions. Report from our laboratory has also shown a possible mechanism how some of these ROS escape the antioxidant system of RBC to produce the heme degradation products and may also get released to the neighboring cells. Our work also shows that increase in these heme degradation products (a marker of RBC oxidative stress) may contribute to the reduced functionality of RBCs making them less deformable, which may lead to poor oxygen delivery to tissues.