Chapter category: Ischemia-Reperfusion
Superoxide Dismutase Mimetics and Acute Renal Failure
Chapter authors:
Prabal Kumar Chatterjee and Christoph Thiemermann
Acute renal failure (ARF) affects as many as 5% of all hospitalised patients and has a high rate of mortality. To date, clinical treatment of patients suffering from ARF is still largely supportive and dialysis remains the only viable therapy. Therefore, the development of novel interventions with which to treat ARF remains a topic of great interest. Renal injury caused by ischemia/reperfusion (I/R) is the most common cause of ARF. Evidence has accumulated for the generation of reactive oxygen species (ROS) during renal I/R, particularly the superoxide anion (O2?-) and its two reaction products (hydroxyl radical [OH?] and peroxynitrite [ONOO-]) and their role in the development of I/R injury and subsequent ARF. Under physiological conditions, endogenous antioxidant enzymes such as superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase (CAT) provide adequate defence against low level oxidant stress. However, under pathophysiological conditions such as those which prevail during I/R, oxidant stress caused by an imbalance of oxidant/antioxidant capacity means that these defence mechanisms are overcome, leading to recognisable ROS-mediated injury. Furthermore, renal I/R leads not only to an increase in O2?- production but also to a rapid depletion of antioxidant enzymes such as SOD, GPx and CAT. Numerous studies have investigated the potential benefits of exogenous SOD in the prevention of renal injury, but the data are conflicting. Removal of O2?- (and thus of OH? and ONOO-) by SOD mimetics have been shown to prevent the dysfunction and injury associated with renal I/R and inflammation. This chapter aims to review the current evidence that SOD plays an important role in renal I/R (and consequent ARF) and the latest reports describing the beneficial role of SOD mimetics. The prospects for the use of SOD mimetics as an intervention against renal I/R injury and for the potential therapy of ARF are also discussed.
