Effects of Reactive Oxygen Species on Tubular Transport along the Nephron

Reactive oxygen species (ROS) are oxygen-containing molecules naturally occurring in both inorganic and biological chemical systems. Due to their high reactivity and potentially damaging effects to biomolecules, cells express a battery of enzymes to rapidly metabolize them to innocuous intermediaries. Initially, ROS were considered by biologists as dangerous byproducts of respiration capable of causing oxidative stress, a condition in which overproduction of ROS leads to a reduction in protective molecules and enzymes and consequent damage to lipids, proteins, and DNA. In fact, ROS are used by immune systems to kill virus and bacteria, causing inflammation and local tissue damage. Today, we know that the functions of ROS are not so limited, and that they also act as signaling molecules mediating processes as diverse as gene expression, mechanosensation, and epithelial transport. In the kidney, ROS such as nitric oxide (NO), superoxide (O₂^-), and their derivative molecules hydrogen peroxide (H₂O₂) and peroxynitrite (ONO₂^-) regulate solute and water reabsorption, which is vital to maintain electrolyte homeostasis and extracellular fluid volume. This article reviews the effects of NO, O₂^-, ONO₂^-, and H₂O₂ on water and electrolyte reabsorption in proximal tubules, thick ascending limbs, and collecting ducts, and the effects of NO and O₂^- in the macula densa on tubuloglomerular feedback.