Prediction of soman-induced cerebral damage by distortion product otoacoustic emissions.
The organophosphorus nerve agent soman is an irreversible cholinesterase (ChE) inhibitor that can produce long-lasting seizures and seizure-related brain damage (SRBD) in which acetylcholine and glutamate are involved. Since these neurotransmitters play a key-role in the auditory function, it was hypothesized that a hearing test may be an efficient way for detecting the central effects of soman intoxication. In the present study, distortion product otoacoustic emissions (DPOAEs), a non-invasive audiometric method, were used in rats administered with soman (70 μg/kg). Four hours post-soman, DPOAE intensities were significantly decreased. They returned to baseline one day later. The amplitude of the temporary drop of the DPOAEs was well related to the severity of the intoxication. The greatest change was recorded in the rats that survived long-lasting convulsions, i.e. those that showed the highest ChE inhibition in brain and severe encephalopathy. Furthermore, the administration, immediately after soman, of a three-drug therapy composed of atropine sulfate, HI-6 and avizafone abolished the convulsions, the transient drop of DPOAEs at 4h and the occurrence of SRBD at 28 h without modifying brain ChE inhibition. This showed that DPOAE change was not directly related to soman-induced inhibition of cerebral ChE but rather to its neuropathological consequences. The present findings strongly suggest that DPOAEs represent a promising non-invasive tool to predict SRBD occurrence in nerve agent poisoning and to control the efficacy of a neuroprotective treatment.
Carpentier
Pierre
P
Institut de Recherche Biomédicale des Armées, Département de Toxicologie et Risques Chimiques, 24 Avenue des Maquis du Grésivaudan, BP 87, 38702 La Tronche Cédex, France. pierrecarpentier@crssa.net
Pouyatos
Benoit
B
Dorandeu
Frédéric
F
Campo
Pierre
P
Baille
Valérie
V
Foquin
Annie
A
Job
Agnès
A
D000818:Animals; D001930:Brain Injuries / Q000139:chemically induced* / Q000473:pathology* / Q000517:prevention & control; D003051:Cochlea / Q000187:drug effects / Q000502:physiology; D005544:Forecasting; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use; D017084:Otoacoustic Emissions, Spontaneous / Q000187:drug effects* / Q000502:physiology*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D012640:Seizures / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control; D012999:Soman / Q000633:toxicity*
D018696:Neuroprotective Agents; D012999:Soman