Effect of lipo-pro-prostaglandin E1, AS-013 on rat inner ear microcirculatory thrombosis.
We investigated effects of lipo-pro-prostaglandin E1 (lipo-[11alpha, 13E, 15S]-11,15-dihydroxy-9-[1-oxobutoxy]-prosta-8, 13-dien-1-oic acid butyl ester), AS-013 in two models of hearing disturbance and equilibrium dysfunction induced by rat inner ear microcirculatory thrombosis. Inner ear microcirculatory thrombosis was induced by photochemical reaction between systemic injection of Rose Bengal and irradiation of green light to the cochlea and vestibule. Photochemical reaction causes endothelial injury followed by platelet adhesion, aggregation and formation of a platelet- and fibrin-rich thrombus. In the hearing disturbance model, a compound cochlear nerve action potential was recorded by electrocochleography every minute. Photochemical reaction induced inner ear microcirculatory thrombosis, followed by disappearance of the action potential. AS-013 significantly (P<0.05) prolonged time to disappearance of the action potential compared with control group. In the equilibrium dysfunction model, the irradiation to the vestibule was applied for 10 min after Rose Bengal injection. The behavior of rats in the swimming test and nystagmus were observed 24 h after the completion of irradiation. In the swimming test, two of 12 animals treated with AS-013 showed no rotating about their longitudinal axes, which indicates equilibrium dysfunction and the duration of well-balanced swimming prolonged. AS-013 suppressed the appearance of nystagmus. These results suggest that lipo-pro-prostaglandin E1, AS-013 may prevent hearing disturbance and equilibrium dysfunction due to inner ear microcirculatory disorders.
Hokamura
K
K
Department of Pharmacology, Hamamatsu University School of Medicine, Japan.
Umemura
K
K
Nakamura
N
N
Watanabe
M
M
Takashima
T
T
Nakashima
M
M
D000200:Action Potentials / Q000502:physiology; D000818:Animals; D001300:Audiometry, Evoked Response; D003051:Cochlea / Q000473:pathology*; D003056:Cochlear Nerve / Q000187:drug effects* / Q000528:radiation effects; D004195:Disease Models, Animal; D006311:Hearing Disorders / Q000503:physiopathology; D008027:Light / Q000009:adverse effects; D008833:Microcirculation / Q000528:radiation effects*; D017319:Photosensitizing Agents / Q000494:pharmacology; D011460:Prostaglandins F / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D012395:Rose Bengal / Q000378:metabolism; D013927:Thrombosis / Q000139:chemically induced / Q000473:pathology*; D014722:Vestibule, Labyrinth / Q000473:pathology*
D017319:Photosensitizing Agents; D011460:Prostaglandins F; D017382:Reactive Oxygen Species; D012395:Rose Bengal; C110507:Ecraprost