[Neurotoxicity in sodium azide poisoning].
The effects of sodium azide administration on the central cholinergic functions were investigated utilizing mice to evaluate the neurotoxicity in the acute poisoning. Seven oral doses of the toxicant, ranging in dosage from 12.3 to 59.3 mg/kg, based upon a multiple of 1.3 x 27 mg/kg (an empirical LD50 for mice) or 27 mg/kg divided by 1.3 to calculate the lower three doses, were administered to facilitate the acute signs and to observe behavior. The behavior included locomotor activity, rectal temperature and rotarod performance which are convenient for the evaluation of central cholinergic involvement even if it may be partial, since no behavioral methods to study totally the cholinergic system have been known. Measurements of the activities of acetylcholinesterase (AChE) and choline acetyltransferase (ChAT), enzymes that hydrolyze and synthesize acetylcholine (ACh) and high-affinity choline uptake (HACU), a rate-limiting step in the synthesis of ACh, were determined in the presence of various concentrations of sodium azide in vitro. Adult (12-15 weeks) female ICR strain mice were utilized in this study. Mice were orally given sodium azide in doses from 27 to 59.3 mg/kg and appeared sedated within 5 min. Next we observed hyperpnea and dyspnea, which were followed by seizure and death for mouse groups which received more than 35.1 mg/kg. Oral administration of the sodium azide solution produced an increase in locomotor activity for the 12.3 mg/kg group and a decrease for the higher doses (ranging from 16.0 to 27.0 mg/kg). The sodium azide administration suppressed rectal temperature dose-dependently as well as rotarod performance at high doses (20.8 and 27.0 mg/kg). Such behavioral changes elicited by sodium azide administration suggest an involvement of the central cholinergic system. Sodium azide also caused a measured decrease in the activity of AChE, but an increase in the activities of ChAT and HACU, dose-dependently, in vitro. From the results obtained from the behavioral and the in vitro experiments, we concluded that acute sodium azide poisoning significantly affects the central cholinergic system.
Fujimura
Takasuke
T
Matsuzono Animal Hospital.
Kobayashi
Haruo
H
Suzuki
Tadahiko
T
Sato
Itaru
I
Hara
Shigeo
S
D000109:Acetylcholine / Q000378:metabolism; D000110:Acetylcholinesterase / Q000378:metabolism; D000208:Acute Disease; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001831:Body Temperature / Q000187:drug effects; D002490:Central Nervous System / Q000187:drug effects* / Q000378:metabolism; D002794:Choline; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D002799:Cholinergic Fibers / Q000187:drug effects* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D051379:Mice; D008813:Mice, Inbred ICR; D009043:Motor Activity / Q000187:drug effects; D012007:Rectum / Q000502:physiology; D019810:Sodium Azide / Q000506:poisoning* / Q000633:toxicity
D019810:Sodium Azide; D002795:Choline O-Acetyltransferase; D000110:Acetylcholinesterase; D002794:Choline; D000109:Acetylcholine