The contribution of phospholipase A2 to the cochlear dysfunction induced by transient ischemia.
The objective of the present study was to examine whether mepacrine, a commonly used phospholipase A2 inhibitor, decreases ischemic damage to the cochlea. Transient ischemia of the cochlea was induced in albino guinea pigs for 15, 30 or 60 min by pressing the labyrinthine artery at the porus acusticus internus. The animals were intraperitoneally given mepacrine or physiological saline solution (PSS) 20 min prior to ischemia. Although mepacrine failed to alleviate the post-ischemic threshold shift of compound action potential (CAP) in case of 60 min ischemia, a statistically significant reduction in the CAP threshold shift was observed in the mepacrine-treated animals after 15 and 30 min ischemia. However, there was no statistically significant difference in the post-ischemic threshold shift of cochlear microphonic between the mepacrine-given and the PSS-given animals. Furthermore, mepacrine partially alleviated ischemia-induced swelling of radial afferent dendrites of primary auditory neurons. These results suggest that excessive activation of phospholipase A2 plays an injury-producing role at least by enhancing excitotoxicity in ischemia-reperfusion injury of the cochlea.
Tabuchi
K
K
Department of Otolaryngology, Institute of Clinical Medicine, University of Tsukuba, 1-1-1 Tennodai, 305-8575, Tsukuba, Japan.
Ito
Z
Z
Tsuji
S
S
Wada
T
T
Takahashi
K
K
Hara
A
A
Kusakari
J
J
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D003051:Cochlea / Q000098:blood supply* / Q000503:physiopathology*; D003055:Cochlear Microphonic Potentials / Q000187:drug effects; D003712:Dendrites / Q000648:ultrastructure; D004056:Differential Threshold / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006168:Guinea Pigs; D007511:Ischemia / Q000473:pathology / Q000503:physiopathology*; D009475:Neurons, Afferent / Q000648:ultrastructure; D010741:Phospholipases A / Q000037:antagonists & inhibitors / Q000502:physiology*; D054467:Phospholipases A2; D011796:Quinacrine / Q000494:pharmacology; D012039:Regional Blood Flow
D004791:Enzyme Inhibitors; D010741:Phospholipases A; D054467:Phospholipases A2; D011796:Quinacrine