title: Distortion product otoacoustic emissions as non-invasive biomarkers and predictors of soman-induced central neurotoxicity: a preliminary study.
abstract: The organophosphorus nerve agent soman is an irreversible cholinesterase (ChE) inhibitor that can produce long-lasting seizures and brain damage in which the neurotransmitters acetylcholine and glutamate are involved. These same neurotransmitters play key-roles in the auditory function. It was then assumed that exploring the hearing function may provide markers of the central events triggered by soman intoxication. In the present study, distortion product otoacoustic emissions (DPOAEs), a non-invasive audiometric method, were used to monitor cochlear functionality in rats administered with a moderate dose of soman (45 microg/kg). DPOAEs were investigated either 4h or 24h post-challenge. In parallel, the effects of soman on whole blood and brain ChE activity and on brain histology were also studied. The first main result is that DPOAE intensities were significantly decreased 4h post-soman and returned to baseline at 24h. The amplitude changes were well related to the severity of symptoms, with the greatest change being recorded in the rats that survived long-lasting convulsions. The second main result is that baseline DPOAEs recorded 8 days before soman appear to predict the severity of symptoms produced by the intoxication. Indeed, the lowest baseline DPOAEs corresponded to the occurrence of long-lasting convulsions and brain damage and to the greatest inhibition in central ChE. These results thus suggest that DPOAEs represent a promising non-invasive tool to assess and predict the central consequences of nerve agent poisoning. Further investigations will be carried out to assess the potential applications and the limits of this non-invasive method.
authors.affiliation: Centre de Recherches du Service de Santé des Armées, Département des Facteurs Humains, BP 87, 38702 La Tronche Cedex, France. agnes.job@laposte.net
authors.forename: Agnès
authors.initials: A
authors.lastname: Job
authors.forename: Valérie
authors.initials: V
authors.lastname: Baille
authors.forename: Frédéric
authors.initials: F
authors.lastname: Dorandeu
authors.forename: Benoît
authors.initials: B
authors.lastname: Pouyatos
authors.forename: Annie
authors.initials: A
authors.lastname: Foquin
authors.forename: Claire
authors.initials: C
authors.lastname: Delacour
authors.forename: Josiane
authors.initials: J
authors.lastname: Denis
authors.forename: Pierre
authors.initials: P
authors.lastname: Carpentier
mesh_terms: D000161:Acoustic Stimulation; D000818:Animals; D001299:Audiometry / Q000379:methods; D001300:Audiometry, Evoked Response / Q000379:methods; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D001923:Brain Chemistry / Q000187:drug effects; D002800:Cholinesterase Inhibitors / Q000008:administration & dosage / Q000097:blood / Q000633:toxicity; D003051:Cochlea / Q000187:drug effects / Q000503:physiopathology; D007279:Injections, Subcutaneous; D008297:Male; D020258:Neurotoxicity Syndromes / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology; D017084:Otoacoustic Emissions, Spontaneous / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D012720:Severity of Illness Index; D012999:Soman / Q000008:administration & dosage / Q000097:blood / Q000633:toxicity*; D016019:Survival Analysis; D013997:Time Factors
chemical_list: D002800:Cholinesterase Inhibitors; D012999:Soman