The purpose of this study was to assess the protective effects of allopurinol, a blocker of free oxygen radical (FOR) formation, and superoxide dismutase-polyethylene glycol (SOD-PEG), a scavenger of FORs, on Ischemic and reperfusion-induced cochlear damage. Fifteen Wistar Kyoto rats (WKY) were randomly assigned to three groups: (1) a control group (5 animals) that was exposed to 15 minutes of cochlear ischemia by clamping the anterior inferior cerebellar artery (AICA), followed by 15 minutes of reperfusion as documented by laser Doppler flowmetry; (2) a drug-treated group (5 animals) that received allopurinol before ischemia/reperfusion; and (3) a drug-treated group (5 animals) that received SOD-PEG before ischemia/reperfusion. In the control group, the tone burst-evoked compound action potential (CAP) recorded from the round window (RW) of the cochlea was abolished, and the cochlear microphonic (CM) was reduced after ischemia. In contrast, both allopurinol and SOD-PEG–treated animals showed post-reperfusion sensitivity in CAP and CM measures. We interpret these results to indicate that damage to the cochlea from ischemia and subsequent reperfusion can be attenuated by pretreatment with allopurinol or SOD-PEG. This provides indirect evidence that FORs may be partially responsible for cochlear damage resulting from ischemic conditions.
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References
1.
McCordJM. Mechanisms of disease: Oxygen-derived free radicals in postischemic tissue. N Engl J Med1985; 312: 159–63.
2.
KelleyWNWyngardenJB. Effects of allopurinol on purine synthesis in cultured human cells. J Clin Invest1970; 49: 602–9.
3.
GrangerDNRutiliGMcCordJM. Superoxide radicals in feline intestinal ischemia. Gastroenterology1981; 81: 22–9.
4.
CunninghamSKKeavenzTV. Effect of A xanthine oxidase inhibitor on adenine nucleotide degradation in hemorrhagic shock. Eur Surg Res1978; 10: 305–13.
5.
AdachiHMotomatsuKYaraI. Effect of allopurinol on patients undergoing open heart surgery. Jpn Circ J1979; 43: 395–401.
6.
TaylorMDPalmerGCCallahanAS. Protective action by meth-ylprednisolene, allopurinol, and indomethacin against stroke-induced damage to adenylate cyclase in gerbil cerebral cortex. Stroke1983; 15: 329–35.
7.
DemopulosHBFlanmESPietronigroDDSeligmanML. The free radical pathology and the microcirculators in the major central nervous system disorders. Acta Physiol Scand (Suppl) 1980; 492: 91–119.
8.
ItohTKawakamiMYamauchiYShimizuSNakamuralM. Effect of allopurinol on ischemia and reperfusion-induced cerebral injury in spontaneously hypertensive rats. Stroke1986; 17: 1284–7.
9.
RoyRSMcCordJM. Superoxide and ischemia: Conversion of xanthine dehydrogenase to xanthine oxidase. Oxygen radicals and their scavenger systems. Vol. 2. In: GreenwaldMCohenRA, eds. Cellular and medical aspects. Amsterdam: Elsevier, 1983; 145–53.
10.
RaichleMEDeVivoDCHanawayJ. Disorders of cerebral circulation. In: EliassonSGPrenskyALHardinWB, eds. Neurological pathophysiology. New York: Oxford Press, 1978; 278–304.
11.
McCordJMFridovichI. The reduction of cytochrome C by milk xanthine oxidase. J Biol Chem1968; 243: 5753–60.
12.
WingKG. Studies of basic cochlear physiology and the energy-metabolism of the cochlear response in the cat. Acta Otolaryngol (Stockh)1959; 148: 1–97.
13.
FernandezCAlzateR. Modification of cochlear responses by oxygen deprivation. Arch Otolaryngol1959; 69: 82–94.
14.
KubayashiTIseIMarcosDCThalmannR. Effect of iodo-acetic acid upon cochlear potentials. Acta Otolaryngol (Stockh)1987; 435: 46–54.
15.
WoolfNKAllenRFHarrisJP. Development of mammalian endocochlear potential: Normal ontogeny and effects of anoxia. Am J Physiol1986; 250: 493–8.
16.
KimuraRPerlmanHB. Extensive venous obstruction of the labyrinth. Ann Otol Rhinol Laryngol1956; 65: 332–50.
17.
PerlmanHBKimuraR. Experimental obstruction of venous drainage and arterial supply of the inner ear. Ann Otol Rhinol Laryngol1957; 66: 537–46.
18.
PerlmanHBFernandezC. Experiments on temporary obstruction of the internal auditory artery. Laryngoscope1959; 69: 591–613.
19.
OkumuraH. Perilymph as a medium of oxygen supply for the organ of Corti. Arch Klin Exp Ohr, Nas, Kehlkopfheilk1970; 195: 257–65.
20.
HonrubiaVJohnstoneBMButlerRA. Maintenance of cochlear potentials during asphyxia. Acta Otolaryngol1965; 60: 105.
21.
BrownMCNuttallALMastaRLLawrenceM. Cochlear inner ear cells: Effects of transient asphyxia and intracellular potentials. Hear Res1983; 9: 131–44.
22.
NuttallALLawrenceM. Intracellular potential changes of Corti's organ with anoxia. Arch Otolaryngol1979; 105: 574–8.
23.
NuttallAL. Dynamic aspects of guinea pig inner hair cell receptor potentials with transient asphyxia. Hear Res1984; 16: 1–16.
24.
KonishiTButlerRFernandezC. Effect of anoxia on cochlear potentials. J Acoust Soc Am1961; 33: 349–56.
25.
AxelssonAVertesDMillerJ. Immediate noise effects on cochlear vasculature in the guinea pig. Acta Otolaryngol1981; 91: 237–46.
26.
AxelssonAVertesD. Histologic findings in cochlear vessels after noise. In: HamernikRPHendersonDSalviR, eds. New perspectives on noise-induced hearing loss. New York: Raven Press, 1982; 49–68.
27.
HawkinsJEJohnssonLGPrestonRE. 1. Cochlear microvas-culature in normal and damaged ears. Laryngoscope1972; 82: 1091–103.
28.
JohnssonLHawkinsJE. Symposium on basic ear research. II. Strial atrophy in clinical and experimental deafness. Laryngoscope1972; 82: 1105–25.
29.
RandolfHBHauptHScheibeF. Cochlear blood flow following temporary occlusion of the cerebellar arteries. Eur Arch Otorhinolaryngol1990; 247: 226–8.
BrownMCNuttallALMastaRI. Intracellular recordings from cochlear inner hair cells: Effects of stimulation of the crossed olivocochlear efferents. Science1983; 222: 69–72.
32.
BrownMCSmithDINuttallAL. Anesthesia and surgical trainees: Their influence on the guinea pig compound action potential. Hear Res1983; 10: 345–58.
33.
DolanDFNuttallAL. Masked cochlear whole-nerve response intensity functions altered by electrical stimulation of the crossed olivocochlear bundle. J Acoust Soc Am1988; 83: 1081–6.
34.
IansekRPackhamDAspeyBSHarrisonM. An assessment of the possible protective effect of allopurinol in acute stroke. J Neurol Neurosurg Psychiatry1986; 49: 5895–587.
35.
TaylorMDMellertTKPermentierJLEddyLJ. Pharmacological protection of reoxygenation damage to in vitro brain slice tissue. Brain Res1985; 347: 268–73.
36.
Del MaestroRFBjorkJArforsKE. Increase in microvascular permeability induced by enzymatically generated free radicals. II. Role of superoxide anion radical, hydrogen peroxide, and hydroxyl radical. Microvasc Res1981; 22: 255–70.
37.
HallEDPazaraKEBraughlerJM. 21-amino steroid lipid peroxidation inhibitor U74006F protects against cerebral ischemia in gerbils. Stroke1988; 19: 997–1002.
38.
SilviaRCPlerceyMCHoffmanWEChaseRLBraughlerJMTangAH. U74006F, an inhibitor of lipid peroxidation protects against lesion development following experimental stroke in the cat: Histological and metabolic analysis. Soc Neurosci Abs1987; 13: 1495.
39.
AndersonEKBraughlerJMHallEDWatersTRMcCallJMMeansED. The 21-aminosteroid, U74006F enhances neurological recovery in a model of spinal cord compression injury. Soc Neurosci Abs1987; 13: 1499.
40.
KimDYakshTRomeroSSundtT. Production of uric acid in cerebrospinal fluid after subarachnoid hemorrhage in dogs: Investigation of the possible role of xanthine oxidase in chronic vasospasm. Neurosurgery1987; 21: 39–44.
41.
ReibelDKRovettoMJ. Myocardial ATP synthesis and mechanical function following oxygen deficiency. Am J Physiol1968; 214: 1374–7.
42.
ImaiSRileyALBerneRM. Effect of ischemia and adenine nucleotides in cardiac and skeletal muscles. Circ Res1964; 15: 443–9.
43.
NataleJESchuttRJHallEDBraughlerJMD'AlecyLG. Effect of the aminosteroid U74006F after cardiopulmonary arrest in dogs. Stroke1988; 19: 1371–8.
44.
JonesCECrowellJWSmithE. Significance of increased blood uric acid following extensive hemorrhage. Am J Physiol1968; 214: 1374–7.
45.
CunninghamSKKearneyTV. Effect of xanthine oxidase inhibition on adenine nucleotide degradation in haemorrhagic shock. Eur Surg Res1978; 10: 305–13.
46.
CrowellJWJonesCESmithEE. Effect of allopurinol on hemorrhagic shock. Am J Physiol1969; 216: 944–8.
47.
HiblerN. Novacin als Therpeutikum in Hals-Nasen-Ohren-Gebiet. Monatsschr Ohrenkeild1948; 82: 441.
48.
KellerhalsBHippertFPfaltzCR. Treatment of acute acoustic trauma with low molecular weight dextran. Pract Otorhinolaryngol1971; 33: 260.
49.
FischU. Management of sudden deafness. Otolaryngol Head Neck Surg1983; 91: 3.
50.
HawkinsJE. The role of vasoconstriction in noise-induced hearing loss. Ann Otol Rhinol Laryngol1971; 80: 903–13.
51.
ThornePRNuttallAL. Laser Doppler measurements of cochlear blood flow during loud sound exposure in the guinea pig. Hear Res1987; 27: 1–10.
52.
PiersonMGMollerAR. Prophylaxis of kanamycin-induced ototoxicity by a radioprotectant. Hear Res1981; 4: 79–87.
53.
BockGRYatesGKMillerJJMoorjaniP. Effects of n-acetylcysteine on kanamycin ototoxicity in the guinea pig. Hear Res1983; 9: 255–62.
54.
BergmannK. Experiments on the medicamental treatment of the noise-induced cochlear damage: The effect on the RMP of the cochlea (guinea pig) after noise. Arch Otorhinolaryngol1976; 212: 171–7.
55.
SeidmanMDQuirkWS. A description of an anterior inferior cerebellar arterial network supplying the rat cochlea. Submitted to AJO.
56.
BetzAL. Identification of hypoxanthine transport and xanthine oxidase activity in brain capillaries. J Neurochem1985; 44: 574–9.
57.
BetzLMartzDRandallJ. Free radicals, ischemia, xanthine oxidase, and the brain capillary. In: OwmanCHWidnerH, eds. Pathophysiology of the blood-brain barrier. New York: Elsevier Science Publishing, Biomed Division, 1990; 333–41.
58.
CanlonBSchachtJ. Acoustic stimulation alters deoxyglucose uptake in the mouse cochlea and inferior colliculus. Hear Res1983; 10: 217–26.
59.
QuirkWShapiroBNuttallAMillerJ. Noise-induced changes in red blood cell velocity in lateral wall vessels of the rat cochlea. Hear Res1991; 52: 217–24.
