title: Trimetazidine prevents cochlear lesions induced by intraperitoneal and perilymphatic administration of kainic acid.
abstract: The protective activity of trimetazidine (TMZ) against cochlear neurotoxicity induced by intraperitoneal and intracochlear administration of kainic acid (KA) has been analyzed. The amplitude of the CAP N1 wave was significantly higher in KA rats pretreated with TMZ, independently of the administration route, than in those only treated with KA. However, CAP N1 amplitude of both TMZ pretreated and non-pretreated animals was always lesser than the N1 wave amplitude observed in the control group. The CAP N1 latency did not show any significant difference between KA and TMZ+KA groups except at high intensities of 8 and 12 kHz. As a complementary control, we have demonstrated that the intraperitoneal administration of TMZ (5 mg/kg) alone did not affect either the electrophysiological activity or the morphology of the auditory nerve. Morphological results fit well with electrophysiology. Some isolated swollen afferent fibers were observed in TMZ+KA cochleae, the swollen dendrites being sparser than in the KA only treated animals. In TMZ+KA animals, the cochlear apical coils were less affected than the basal coils. Our results are in agreement with recent clinical studies and suggest that TMZ could be an active drug on cochlear impairment linked to hypoxic-ischaemic syndromes.
authors.affiliation: Department of Surgery II (ORL), Faculty of Medicine and Center of Cell Culture (CAI-UCM), Complutense University of Madrid, Apartado de Correos 60075, 28080, Madrid, Spain. loyzaga@eucmax.sim.ucm.es
authors.forename: P
authors.initials: P
authors.lastname: Gil-Loyzaga
authors.forename: E
authors.initials: E
authors.lastname: Hernández
authors.forename: F
authors.initials: F
authors.lastname: Carricondo
authors.forename: F
authors.initials: F
authors.lastname: Simón
authors.forename: J
authors.initials: J
authors.lastname: Poch-Broto
mesh_terms: D000818:Animals; D004594:Electrophysiology; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology*; D007272:Injections, Intralymphatic; D007274:Injections, Intraperitoneal; D007608:Kainic Acid / Q000494:pharmacology*; D008297:Male; D008854:Microscopy, Electron; D009410:Nerve Degeneration / Q000139:chemically induced / Q000503:physiopathology*; D009498:Neurotoxins / Q000494:pharmacology; D009925:Organ of Corti / Q000166:cytology / Q000648:ultrastructure; D051381:Rats; D020318:Rats, Long-Evans; D011930:Reaction Time / Q000502:physiology; D014292:Trimetazidine / Q000494:pharmacology*; D014665:Vasodilator Agents / Q000494:pharmacology*; D000159:Vestibulocochlear Nerve / Q000166:cytology / Q000502:physiology* / Q000648:ultrastructure
chemical_list: D018690:Excitatory Amino Acid Agonists; D009498:Neurotoxins; D014665:Vasodilator Agents; D014292:Trimetazidine; D007608:Kainic Acid