The NO/ONOO- cycle as the etiological mechanism of tinnitus.

Peripheral tinnitus is a good candidate for inclusion under the NO/ONOO cycle etiological mechanism, fitting each of the five principles of this mechanism. Cases of tinnitus are initiated by at least 11 short-term stressors increasing nitric oxide or other cycle mechanisms. Such cycle elements as N-methyl-D-aspartate activity; oxidative stress; nitric oxide; peroxynitrite; vanilloid activity; NF-kappaB activity; and intracellular calcium levels are all reported to be elevated in tinnitus. Tinnitus is comorbid with some putative NO/ONOO- cycle diseases. Most important, multiple agents that down-regulate NO/ONOO- cycle biochemistry are reported to be helpful in the treatment of tinnitus and related diseases. Previous studies suggested that NO/ONOO cycle diseases may be best treated with complex combinations of agents predicted to lower NO/ONOO- cycle biochemistry, and such combinations may be helpful in tinnitus treatment. Other inner-ear-related defects, such as acute or progressive hearing loss, vertigo, and dizziness, may also be NO/ONOO cycle diseases.