Toxic effects of sarin in rats at three months following single or repeated low-level inhalation exposure.
Male albino Wistar rats were once or repeatedly exposed to three various low concentrations of sarin for 60 min. in the inhalation chamber. The clinical status of control as well as sarin-poisoned rats was tested 3 months after exposure to sarin using biochemical, haematological, neurophysiological, behavioural and immunotoxicological methods. While biochemical and haematological parameters, including the activities of cholinesterases in erythrocytes, plasma and various organs (brain, diaphragm), did not differ from the control values regardless of the sarin concentration used, few signs of sarin-induced neurotoxicity and immunotoxicity in sarin-poisoned rats were demonstrated. This was especially true when the single exposure of rats to non-convulsive symptomatic concentration and repeated exposure of rats to clinically asymptomatic concentration of sarin was used. In rats repeatedly poisoned with clinically asymptomatic concentrations of sarin, the alteration of the gait characterized by ataxia, the increase in the stereotyped behaviour, the increase in the excitability of the central nervous system following the administration of the convulsive drug pentamethylenetetrazol were observed. In rats poisoned with non-convulsive symptomatic concentration of sarin, the subtle supression of spontaneous, as well as lipopolysaccharides-stimulated, proliferation of spleen lymphocytes and the bactericidal activity of peritoneal macrophages was primarily observed besides the signs of neurotoxicity. Our findings confirm that both non-convulsive symptomatic and clinically asymptomatic concentrations of sarin can only cause very few, subtle long-term signs of neurotoxicity and immunotoxicity in sarin-poisoned rats when the rats were exposed to asymptomatic sarin concentrations repeatedly.
Kassa
J
J
Purkyne Military Medical Academy, Hradec Králové, Czech Republic. kassa@pmfhk.cz
Pecka
M
M
Tichý
M
M
Bajgar
J
J
Koupilová
M
M
Herink
J
J
Krocová
Z
Z
D000280:Administration, Inhalation; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D015415:Biomarkers; D002493:Central Nervous System Diseases / Q000139:chemically induced / Q000503:physiopathology; D002800:Cholinesterase Inhibitors / Q000008:administration & dosage / Q000633:toxicity*; D019963:Clinical Chemistry Tests; D006403:Hematologic Tests; D007107:Immune System / Q000187:drug effects / Q000503:physiopathology; D019570:Inhalation Exposure; D008213:Lymphocyte Activation / Q000187:drug effects / Q000502:physiology; D008214:Lymphocytes / Q000187:drug effects / Q000276:immunology; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012524:Sarin / Q000008:administration & dosage / Q000633:toxicity*; D012640:Seizures / Q000139:chemically induced / Q000503:physiopathology; D018675:Toxicity Tests
D015415:Biomarkers; D002800:Cholinesterase Inhibitors; D012524:Sarin