Changes of acetylcholinesterase activity after long-term exposure to sarin vapors in rats.

In our study, rats were exposed to sarin vapors for 240 min at four different concentrations (0.30, 0.43, 0.58 and 0.82 microg/L) in a whole-body inhalation chamber. The acetylcholinesterase activity (AChE, EC 3.1.1.7) was measured in the whole blood, frontal cortex (FC), pontomedullar area (PM) and basal ganglia (BG). Convulsions and hypersalivation were observed in only one animal of the group exposed to the highest sarin concentration. The decrease in blood AChE activity was significant in all animals exposed to sarin vapors. The highest inhibition of AChE activity (61%) was determined in animals exposed to sarin vapors at a concentration of 0.82 microg/L. In the PM, AChE activity was decreased in all experimental groups, significantly only in the group exposed to sarin vapors at a concentration of 0.58 microg/L. Our results show that in long-term exposure to low concentrations of sarin, the significant decrease in AChE activity in the blood is followed by significant changes of AChE activity in the PM only. This part of the brain seems to be more sensitive than the FC or BG.

Biochemical effects of low level exposure to soman vapour.

The aim of this study was to demonstrate changes in acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) activities, tyrosine aminotransferase activity (TAT) and plasma corticosterone level, neuroexcitability and behavior following 24 hours and 4 weeks of soman sublethal inhalation exposure at low level. AChE activity in erythrocytes and BuChE activity in plasma was decreased (dependent on the concentration of soman) 24 h and 4 weeks after the exposure. Similar decrease in AChE activity in different brain parts was observed. One of stressogenic parameters (TAT) was changed after 24 h exposure only. 4 weeks after the exposure, these parameters (corticosterone and TAT) were in the range of normal values. Behaviour of experimental animals was changed 24 h after the exposure persisting 4 weeks after the exposure as well as neuroexcitability.

The influence of low-level sarin inhalation exposure on the host resistance and immune reaction of inbred BALB/c mice after their infection with Francisella tularensis LVS.

To study the influence of low-level sarin inhalation exposure on immune functions, inbred BALB/c mice were exposed to two low concentrations of sarin for 60 minutes in the inhalation chamber and then infected with Francisella tularensis LVS on the 7th day following the exposure to sarin. 24 hours after infection, the level of some isotypes of antibodies (IgM, IgA) against tularaemia was significantly decreased regardless of the sarin concentration used while the lymphoproliferation was significantly increased regardless of the mitogen and sarin concentration used. Later, the level of some isotypes of antibodies (IgM, IgA) against tularaemia and the vitality of Francisella tularensis LVS was significantly increased in the case of exposure of mice to clinically symptomatic concentration of sarin (7 days after infection) while the lymphoproliferation was significantly decreased regardless of the concentration of sarin when specific tularaemic antigen Ag4 was used as a mitogen (3 weeks after infection). Thus, the results indicate that not only symptomatic but also asymptomatic dose of sarin is able to alter the host resistance and reaction of immune system, especially at 24 hours and 7 days following infection with Francisella tularensis LVS. Nevertheless, the alteration of immune functions following the inhalation exposure to a symptomatic concentration of sarin seems to be more pronounced.

Relationship between plasmatic levels of sarin and cholinesterase inhibition in rats exposed to sarin vapors.

In our study we monitored plasmatic levels of sarin and changes in cholinesterase activities in rats after exposure to sarin vapors at low concentration. Rats were exposed to sarin in inhalation chamber at concentration 1.25 or 2.5 microg/l for 60 minutes. The acetylcholinesterase activity was measured in erythrocytes and in different brain regions (frontal cortex--FC, pontomedullar area--PM, basal ganglia--BG). Butyrylcholinesterase activity and sarin levels were measured in plasma. Acetylcholinesterase activity in erythrocytes as well as butyrylcholinesterase activity in plasma were significantly decreased in both groups of animals after intoxication with sarin. In brain, the significant decrease in acetylcholinesterase activity was measured in FC and PM for both groups. In group exposed to higher concentration of sarin vapors, the plasmatic level of sarin was nearly 2 x higher than in group exposed to sarin at concentration 1.25 microg/l. The linear dependence between plasmatic levels of sarin and AChE activity was assayed in FC region of brain and in erythrocytes, exponential relationship in PM region of brain and for BuChE activity in plasma.

The influence of single or repeated low-level sarin exposure on immune functions of inbred BALB/c mice.

To study the influence of single or repeated low-level sarin inhalation exposure on immune functions, inbred BALB/c mice were exposed to low clinically asymptomatic concentrations of sarin for 60 min. in the inhalation chamber. The evaluation of immune functions was carried out using phenotyping of CD3 (T-lymphocytes), CD4 (helper T-lymphocytes), CD8 (cytotoxic T-lymphocytes) and CD19 (B-lymphocytes) in the lungs, blood and spleen, lymphoproliferation of spleen cells stimulated in vitro by various mitogens (concanavalin A, lipopolysaccharides), phagocyte activity of peritoneal and alveolar macrophages, production of N-oxides by peritoneal macrophages and the measurement of the natural killer cell activity at one week after sarin exposure. The results were compared to the values obtained from control mice exposed to pure air instead of sarin. The results indicate that an asymptomatic dose of sarin is able to alter the reaction of the immune system at one week after exposure to sarin. While the number of CD3 cells in lung was significantly decreased, a slight increase in CD19 cells was observed especially in the lungs after a single sarin inhalation exposure. Lymphoproliferation was significantly decreased regardless of the mitogen and sarin concentration used and the number of low-level sarin exposures. The ability of peritoneal and alveolar macrophages to phagocyte the microbes was also decreased regardless of the number of low-level sarin exposures. The production of N-oxides by peritoneal macrophages was decreased following a single low-level sarin exposure but increased following repeated low-level sarin inhalation exposure. Nevertheless, the changes in the production of N-oxides that reflects a bactericidal activity of peritoneal macrophages was not significant. The natural killer cell activity was significantly higher in the case of inhalation exposure of mice to low concentration of sarin regardless of the number of exposures. Thus, not only organophosphorous insecticides but also nerve agents such as sarin are able to alter immune functions following a single inhalation exposure even at a dose that does not cause clinically manifested intoxication. Generally, the repeated exposure to low concentrations of sarin does not increase the alteration of immune functions compared to the single low-level sarin exposure with the exception of phagocyte activity of alveolar macrophages and natural killer cell activity.

Low-level sarin-induced alteration of immune system reaction in inbred BALB/c mice.

To study the influence of low-level sarin inhalation exposure on immune functions, inbred BALB/c mice were exposed to low concentrations of sarin for 60 min in the inhalation chamber. Two concentrations of sarin were chosen-asymptomatic concentration (LEVEL 1) and non-convulsive symptomatic concentration (LEVEL 2). The evaluation of immune functions was carried out using phenotyping of CD3 (T-lymphocytes), CD4 (helper T-lymphocytes), CD8 (cytotoxic T-lymphocytes) and CD19 cells (B-lymphocytes) in the lungs, blood and spleen, lymphoproliferation of spleen cells stimulated in vitro by various mitogens (concanavalin A, lipopolysaccharides), phagocyte activity of peritoneal and alveolar macrophages, production of N-oxides by peritoneal macrophages and the measurement of the natural killer cell activity at 1 week following sarin exposure. The results were compared to the values obtained from control mice exposed to pure air instead of sarin. The results indicate that not only symptomatic but also asymptomatic dose of sarin is able to alter the reaction of immune system at 1 week following exposure to sarin. While the number of CD3 cells in the lungs was slightly decreased, an increase in CD19 cells was observed especially in the lungs and blood. The reduced proportion of T-lymphocytes is caused by decay of CD4 positive T-cells. Lymphoproliferation was significantly decreased regardless of the mitogen and sarin concentration used. The production of N-oxides by peritoneal macrophages was stimulated after exposure to LEVEL 2 of sarin whereas their ability to phagocyte the microbes was increased after exposure to LEVEL 1. The natural killer cell activity was significantly higher in the case of inhalation exposure of mice to LEVEL 2 of sarin. Thus, not only organophosphorus insecticides but also nerve agents such as sarin are able to alter immune functions even at a dose that does not cause clinically manifested intoxication following the inhalation exposure. Nevertheless, the alteration of immune functions following the inhalation exposure to a symptomatic concentration of sarin seems to be more pronounced.