title: Beneficial effects of a ketamine/atropine combination in soman-poisoned rats under a neutral thermal environment.
abstract: Exposure to organophosphorus (OP) compounds, such as pesticides and the chemical warfare agents (soman and sarin), respectively represents a major health problem and a threat for civilian and military communities. OP poisoning may induce seizures, status epilepticus and even brain lesions if untreated. We recently proved that a combination of atropine sulfate and ketamine, a glutamatergic antagonist, was effective as an anticonvulsant and neuroprotectant in mice and guinea-pigs exposed to soman. Since OP exposure may also occur in conditions of heat strain due to climate, wearing of protective gears or physical exercise, we previously demonstrated that ketamine/atropine association may be used in a hot environment without detrimental effects. In the present study, we assess soman toxicity and evaluate the effects of the ketamine/atropine combination on soman toxicity in a warm thermoneutral environment. Male Wistar rats, exposed to 31°C (easily reached under protective equipments), were intoxicated by soman and treated with an anesthetic dose of ketamine combined with atropine sulfate. Body core temperature and spontaneous locomotor activity were continuously monitored using telemetry. At the end of the warm exposure, blood chemistry and brain mRNA expression of some specific genes were measured. In soman-intoxicated animals, metabolic and genic modifications were related to convulsions rather than to soman intoxication by itself. In the warm environment, ketamine/atropine combination did not produce any side-effect on the assessed variables. Furthermore, the ketamine/atropine combination exhibited beneficial therapeutic effects on soman-intoxicated rats such as a limitation of convulsion-induced hyperthermia and of the increase in some blood chemistry markers.
authors.affiliation: Département de Toxicologie et risques chimiques, IRBA, BP73, 91223 Brétigny sur Orge cedex, France. Electronic address: laure.barbier@irba.fr.
authors.forename: Laure
authors.initials: L
authors.lastname: Barbier
authors.affiliation: Département neurosciences et contraintes opérationnelles, IRBA, BP73, 91223 Brétigny sur Orge cedex, France; Ecole du Val-de-Grâce, 1 place Alphonse Laveran, 75230 Paris, France. Electronic address: frederic.canini@irba.fr.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Canini
authors.affiliation: Département de Toxicologie et risques chimiques, IRBA, BP73, 91223 Brétigny sur Orge cedex, France. Electronic address: celine.giroud@gmail.com.
authors.forename: Céline
authors.initials: C
authors.lastname: Giroud
authors.affiliation: Département de Toxicologie et risques chimiques, IRBA, BP73, 91223 Brétigny sur Orge cedex, France. Electronic address: claire.delacour@irba.fr.
authors.forename: Claire
authors.initials: C
authors.lastname: Beaup
authors.affiliation: Département de Toxicologie et risques chimiques, IRBA, BP73, 91223 Brétigny sur Orge cedex, France. Electronic address: annie.foquin@irba.fr.
authors.forename: Annie
authors.initials: A
authors.lastname: Foquin
authors.affiliation: Département neurosciences et contraintes opérationnelles, IRBA, BP73, 91223 Brétigny sur Orge cedex, France. Electronic address: renaudmaury@hotmail.com.
authors.forename: Renaud
authors.initials: R
authors.lastname: Maury
authors.affiliation: Laboratoire d'analyses biologiques, IRBA, BP73, 91223 Brétigny sur Orge cedex, France. Electronic address: josianedenis38@gmail.com.
authors.forename: Josiane
authors.initials: J
authors.lastname: Denis
authors.affiliation: Unité de biologie moléculaire, IRBA, BP73, 91223 Brétigny sur Orge cedex, France. Electronic address: andre.peinnequin@irba.fr.
authors.forename: André
authors.initials: A
authors.lastname: Peinnequin
authors.affiliation: Département de Toxicologie et risques chimiques, IRBA, BP73, 91223 Brétigny sur Orge cedex, France; Ecole du Val-de-Grâce, 1 place Alphonse Laveran, 75230 Paris, France. Electronic address: frederic.dorandeu@irba.fr.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Dorandeu
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000627:therapeutic use*; D001285:Atropine / Q000627:therapeutic use*; D001831:Body Temperature / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D001930:Brain Injuries / Q000139:chemically induced / Q000188:drug therapy; D002619:Chemical Warfare Agents / Q000633:toxicity*; D002802:Cholinesterases / Q000097:blood; D003345:Corticosterone / Q000097:blood; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D004827:Epilepsy / Q000139:chemically induced* / Q000188:drug therapy*; D005334:Fever / Q000139:chemically induced / Q000188:drug therapy; D005786:Gene Expression Regulation / Q000187:drug effects; D007649:Ketamine / Q000627:therapeutic use*; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D012269:Ribosomal Proteins / Q000235:genetics / Q000378:metabolism; D012999:Soman / Q000633:toxicity*; D013997:Time Factors
chemical_list: D000927:Anticonvulsants; D002619:Chemical Warfare Agents; D012269:Ribosomal Proteins; C054675:ribosomal protein P0; D007649:Ketamine; D001285:Atropine; D012999:Soman; D002802:Cholinesterases; D003345:Corticosterone
keywords: Atropine sulfate; Ketamine; Rat; Seizures; Soman; Thermoregulation