Time evolution of noise induced oxidation in outer hair cells: Role of NAD(P)H and plasma membrane fluidity

Background\r\n\r\nNoise exposure impairs outer hair cells (OHCs). The common basis for OHC dysfunction and loss by acoustic over-stimulation is represented by reactive oxygen species (ROS) overload that may affect the membrane structural organization through generation of lipid peroxidation.\r\nMethods\r\n\r\nHere we investigated in OHC different functional zones the mechanisms linking metabolic functional state (NAD(P)H intracellular distribution) to the generation of lipid peroxides and to the physical state of membranes by two photon fluorescence microscopy.\r\nResults\r\n\r\nIn OHCs of control animals, a more oxidized NAD(P)H redox state is associated to a less fluid plasma membrane structure. Acoustic trauma induces a topologically differentiated NAD(P)H oxidation in OHC rows, which is damped between 1 and 6 h. Peroxidation occurs after ~ 4 h from noise insult, while ROS are produced in the first 0.2 h and damage cells for a period of time after noise exposure has ended (~ 7.5 h) when a decrease of fluidity of OHC plasma membrane occurs. OHCs belonging to inner rows, characterized by a lower metabolic activity with respect to other rows, show less severe metabolic impairment.\r\nConclusion and significance\r\n\r\nOur data indicate that plasma membrane fluidity is related to NAD(P)H redox state and lipid peroxidation which may represent key targets for therapeutic rescuing plan from noise insults.