The Protective Effect Of Regulator Of Calcium Homeostasis On Noise-induced Hearing Loss In Guinea Pig

Ionized calcium (Ca²⁺), a second messenger, plays a very important role incellular function. The sustained increase in intracellular (Ca²⁺ overload) is toxic tocells, which leads to cells impairmed, apoptosis or death. Mechanicaloverstimulation and k⁺-induced depolarization, which are in vitro models foracoustic trauma and noise, can increase intracellular Ca²⁺ concentration of haircells (HCs). An abrupt elevation of Ca²⁺ concentration in endolyInph (EL) wasinduced by acoustic overstimulation, too. So, we speculated that noise-inducedhearing loss (NIHL) is related to calcium homeostasis of HCs. The regulators ofcalcium homeostasis, including calciurn channel blocker and indirect stimulator ofCa²⁺ pump, were involved in intracellular Ca²⁺ regulation. The aim of presentstudy was to investigate the possible protective effect of regulators of calciumhomeostasis on NINL through the effect of regulators reducing intracellular Ca²⁺concentration. In order to determine the role of nifedipine in the cochlea, cochlearpotentials were examined in the guinea pig. We measured the concentration ofnifedipine in perilymph (PL) by the high performance liquid chromatograph(HPLC) to explain the cause on the result. The study was divided into follow threepalls.Part one: Nifedipine, an L-tyPe calcium chaxmel blocker was tested usingcochlea potentials (compound action potential (CAP) and cochlea microPhnics(CM)) in gUinea pigs to investigate whether L-tyPe calciurn channel is involved incochlear function. Perilyrnphs of guinea pig were perfused with artificialperilymph solutions containing 0-3pM (0, 0.l5, 0.5, 3pM) nifedipine at a rate of2.5plimin for 2 hours. The effects of nifedipine on noise-induced hearing losswere examined through whole cochlear perfusion with noise exposure (whitenoise l00 dB SPL) in guinea pig. Perilpph of gUinea pig was perfused withartificial perilymph so1utions containing 0-3pM at a rate of 2.5pVmin fOr 2 hourswith noise exposure. The compound action potential (CAP) was evoked by click,and the cochlea microphnics (CM) evoked by tone burst (4 kHz, rise and fall 2 ms,and plateau 20 ms). The CAP and CM were recorded from the round window(RM). Whole cochlear perfusion with nifedipine resulted in an elevated CAPthreshold and a reduction in CM. These changes were dose-related and reversible.Noise exposure resulted in an elevated CAP threshold and a reduction in CM. TheCM inPut/outPut function showed: the nonlinear prOPoties of CM VO hetionchanged into a linearinzing for all grouPs after noise exPosure. There was notsigniticant different in CAP threshold and CM amPlitude betWeen noise+0.l5pMnifedipine group and noise+artificial perilyInPh grouP. There was significantdifferent in CAP threshold and CM amplitude betWeen noise+0.5pM or 3pMnifedipine group and noise+artificial perilymph grOuP. TherefOre, we madeconclusion that nifedipine resulted in a reversible, dose-related suppression ofcochlear function. Nifedipine might have panly protective effect on NIHL exceptthe low concentration (0. l5pM) nifedipine grouP. These findings indirectly provedthat the L-troe Calcium channel exists in the HCs.Part tWo: The effect of nifedipine, an L-tyPe channel blocker, on NIHL wastested in guinea pig. Animals were injected in abdominal cavity with nifedipine(20mg/kg/day) or placebo for 7days and exposed to l20 dB SPL noise for 4 hours.Auditory brainstem response (ABR) was examined befOre and after injection aswell as befOre and after noise exposure. PerilyInph concentraions of nifedipinewere tested by HPLC. There was not significant different in permanent thresholdshift betWeen nifedipine group and control group. PerilyTnph levels of nifedipinewere, ranged from 0. l45yM to 0.359pM, under 0.5pM. The results suggest that theprotective effect of nifedipine on NIHL, at a low peri1yTnph level, not be presented.Part three: The effect of phorbol-l2-myristate-l3-acetate (PMA), a...