Growing knowledge of the role of free radical biology in other diseases and pathologies lend credence to their important role in SNHL. Free radical formation associated with environmental stress from intense noise or sound energy, drugs, aging and trauma play a key role in hearing loss and cell death in the inner ear, as free radicals function as triggers to upregulate necrotic and apoptotic pathways to cell death. Specifically, free radical formation defines a final common cell death pathway inducing pathology from a large variety of etiological factors. Moreover, for the ear and hearing, these factors are potentiated by reduced organ circulation, which is a dramatic feature of noise-induced stress and a significant feature of the aging process.
Free radicals play a key role in pathology from a variety of environmental stress factors. While free radicals are essential for normal cellular biochemistry, in excess free radicals lead to pathology and are important factors in sensorimotor disorders, as well as other neurologic diseases associated with the aging process. Free radicals function as triggers to upregulate necrotic and apoptotic pathways to cell death. They may be either generated as part of the metabolic processes (Ames et al, 1993) of the cell or frequently as side effects of environmental stress factors, such as visible light (Agarwal et al.,1993; Oleinick and Evans, 1998 ) solar and ionizing radiation (Godar and Lucas, 1995; Godar, 1999;  Zhao, et al.; 2007), cigarette smoke (Aoshiba et al. 2001 ) hyper- and hypoxia (Budinger et al., 2002; Wang et al., 2003), drugs (Forge and Schacht, 2000;  Rybak and Ramkumar, 2007 ), or intense noise exposure (Ohinata et al., 2003;  Le Prell et al., 2007 ). Models detailing the pathways to cell death initiated by free radicals have been developed, across a broad range of pathologies in the peripheral and central nervous systems; and importantly the enhanced production of free radicals secondary to cell metabolism and environmental stress agents with aging has been well documented (for review see: Ryter et al., 2007 ).
Given knowledge of the biochemical pathways to cell death, there are a number of sites along any of these pathways that could block cell death; for example, by blocking upregulation of one of the caspases or by inserting Bcl-2 genes into the mitochondrial membrane, or perhaps blocking release of cytochrome c. However, these are each parallel pathways to cell death and if one is blocked others may take its place.
Free radical formation is associated with environmental stress from intense noise, drugs, aging and trauma play a key role in hearing loss and cell death in the inner ear. Moreover, for the ear and hearing, these factors are potentiated by reduced organ circulation (Miller, et al., 2003;  Le Prell et al., 2007 ), which are dramatic features of SNHL. Evidence on the key role of free radicals in cell death in these many fields provided strong theoretical and empirical support for the likelihood of their importance in hearing impairment.
The mitochondria are the source of cellular energy for normal homeostasis and function. In the process of their normal function, mitochondria produce both molecular oxygen and partially reduced forms of oxygen, which become reactive oxygen species (ROS), the pathway to the production of free radicals.
Reactive nitrogen species (RNS) is another pathway to the production of free radicals. Both ROS and RNS act similarly to trigger necrotic or apoptotic cell death pathways (See Figure 1, Mechanism of action for ROS-induced cell death cascade).