**5.4 Reactive oxygen species (ROS) and reactive nitrogen species (RNS)**

During periods of ischemia, ROS and RNS are generated which can promote intracellular damage. Due to electron transport chain alterations, mitochondrial dysfunction ensues leading to reductions in ATP production and with subsequent loss of inner membrane stability resulting in mitochondrial swelling and rupture. With the reintroduction of oxygen during reperfusion, ROS are produced due to reactions of oxygen introduced during reperfusion and possible xanthine oxidase (or mitochondrial sources of ROS). ROS serve to stimulate other cell lines including Kupffer cells to produce proinflammatory cytokines (Diesen & Kuo, 2011). The major ROS are hydroxyl radical (OH•) and hydrogen peroxide.(H2O2). Reactions of ROS such as O<sup>2</sup> -• with NO yield products such as peroxynitrite (ONOO-), a RNS which can be an extremely aggressive oxidant.
