scholarly journals A Comparison of the Neuroprotective Efficacy of Pharmacological Pretreatment and Antidotal Treatment in Soman-Poisoned Rats

2003 ◽  
Vol 46 (3) ◽  
pp. 101-107 ◽  
Author(s):  
Jiří Kassa ◽  
Gabriela Krejčová ◽  
Ivan Samnaliev

1. To study the influence of pharmacological pretreatment (PANPAL or pyridostigmine combined with biperiden) and antidotal treatment (the oxime HI-6 plus atropine) on soman-induced neurotoxicity, male albino rats were poisoned with a lethal dose of soman (54 (g/kg i.m.; 100% of LD50 value) and observed at 24 hours and 7 days following soman challenge. The neurotoxicity of soman was evaluated using a Functional observational battery and an automatic measurement of motor activity. 2. Pharmacological pretreatment as well as antidotal treatment were able to eliminate some of soman-induced neurotoxic effects observed at 24 hours following soman poisoning. The combination of pharmacological pretreatment (PANPAL or pyridostigmine combined with biperiden) and antidotal treatment was found to be more effective in the elimination of soman-induced neurotoxicity in rats at 24 hours following soman challenge in comparison with the administration of pharmacological pretreatment or antidotal treatment alone. To compare both pharmacological pretreatments, the combination of pyridostigmine with biperiden seems to be more efficacious to eliminate soman-induced signs of neurotoxicity than PANPAL. 3. At 7 days following soman poisoning, the combination of pharmacological pretreatment involving pyridostigmine and biperiden with antidotal treatment was only able to completely eliminate somaninduced neurotoxic signs. 4. Thus, our findings confirm that the combination of pharmacological pretreatment and antidotal treatment is able not only to protect the experimental animals from the lethal effects of soman but also to eliminate most soman-induced signs of neurotoxicity in poisoned rats. The pharmacological pretreatment containing pyridostigmine and biperiden appears to be more efficacious to eliminate soman-induced neurotoxic sings than PANPAL.

2010 ◽  
Vol 53 (2) ◽  
pp. 85-91
Author(s):  
Jiří Kassa ◽  
Jana Žďárová Karasová ◽  
Sandra Tesařová ◽  
Kamil Musílek ◽  
Kamil Kuča

The ability of newly developed oximes (K347, K628) to reduce tabun-induced acute neurotoxic signs and symptoms was compared with currently available oximes (obidoxime, HI-6) using a functional observational battery. The neuroprotective effects of the oximes studied (K347, K628, obidoxime, HI-6) combined with atropine on rats poisoned with tabun at a sublethal dose (220 μg/kg i.m.; 80 % of LD50 value) were evaluated. Tabun-induced neurotoxicity was monitored by a functional observational battery and automatic measurement of motor activity at 24 hours following tabun challenge. The results indicate that all tested oximes combined with atropine enable tabun-poisoned rats to survive 24 hours following tabun challenge. Both newly developed oximes (K347, K628) combined with atropine are able to decrease tabun-induced neurotoxicity in the case of sublethal poisonings but they do not eliminate all tabun-induced acute neurotoxic signs and symptoms. Their ability to decrease the tabun-induced acute neurotoxicity is higher than that of the oxime HI-6 and it is slightly slower than the neuroprotective efficacy of obidoxime. As the neuroprotective potency of both newly developed oximes (K347, K628) is not as high as the potency of obidoxime, they are not a suitable replacement for obidoxime for the treatment of acute tabun poisonings.


1999 ◽  
Vol 42 (4) ◽  
pp. 127-131 ◽  
Author(s):  
Jiří Kassa ◽  
Marie Koupilová

1. The neuroprotective effects of antidotes (atropine, obidoxime/atropine mixture, HI-6/atropine mixture) on rats poisoned with soman at a sublethal dose (48 μg/kg i.m.; 60% of LD50 value) were studied. The neurotoxicity was monitored using a functional observational battery (FOB) and an automatic measurement of motor activity. The neurotoxicity of soman was monitored at 24h and 7d following soman poisoning. 2. The results indicate that atropine alone and the oxime HI-6 in combination with atropine seem to be effective antidotal treatment for the elimination of soman-induced neurotoxicity in the case of sublethal poisonings. 3. On the other hand, the combination of obidoxime with atropine appears to be practically ineffective in diminishing neurotoxic soman-induced symptoms. 4. Dealing with neuroprotective effects of antidotes, the oxime HI-6 in combination with atropine seems to be more suitable antidotal mixture than obidoxime in combination with atropine even in the case of sublethal poisoning with nerve agents.


2008 ◽  
Vol 51 (4) ◽  
pp. 215-221 ◽  
Author(s):  
Jiří Kassa ◽  
Jana Žďárová Karasová ◽  
Sandra Tesařová ◽  
Kamil Kuča ◽  
Kamil Musílek

The neuroprotective effects of newly developed oximes (K156, K203) and currently available oximes (obidoxime, HI-6) in combination with atropine in rats poisoned with cyclosarin were studied. The cyclosarin-induced neurotoxicity was monitored using a functional observational battery 24 hours after cyclosarin challenge. The results indicate that a newly developed oxime K156 is able to counteract slightly cyclosarin-induced neurotoxicity while another newly developed oxime K203 is completely ineffective in reducing cyclosarin-induced neurotoxic signs and symptoms. The neuroprotective efficacy of K156 is comparable with commonly used obidoxime and oxime HI-6. Thus, none of the newly developed oximes achieves better neuroprotective efficacy than both commonly used oximes. They are therefore not suitable replacements for antidotal treatment of acute poisonings with cyclosarin.


2002 ◽  
Vol 45 (2) ◽  
pp. 75-78 ◽  
Author(s):  
Jiří Kassa

1. The influence of oximes (pralidoxime, obidoxime, HI-6) and anticholinergic drugs (atropine, benactyzine, biperiden, scopolamine) on the effectiveness of antidotal treatment to eliminate tabun-induced lethal effects was studied in mice. 2. Obidoxime seems to be the most efficacious oxime for the elimination of tabun-induced lethal effects in mice, although the difference in the efficacy of obidoxime and HI-6 is not significant when they are combined with atropine. 3. Obidoxime and HI-6 when combined with centrally acting anticholinergic drugs (benactyzine, biperiden and scopolamine) seem to be more efficacious in the elimination of toxic effects of the lethal dose of tabun than their combination with atropine. 4. The findings support the hypothesis that the choice of acetylcholinesterase reactivators as well as the anticholinergic drug selection are important for the effectiveness of antidotal mixture in the case of antidotal treatment of tabun-induced acute poisoning.


2004 ◽  
Vol 47 (1) ◽  
pp. 13-18 ◽  
Author(s):  
Gabriela Krejčová ◽  
Jiří Kassa

1. To study the influence of antidotes on tabun-induced neurotoxicity, the rats were injected intramuscularly with organophosphate tabun (LD50). The efficacy of choice antidotal treatment consisting of acetylcholinesterase reactivator obidoxime and one of four anticholinergic drugs (atropine, benactyzine, biperiden, scopolamine) was compared. 2. Testing of tabun-induced neurotoxicity progress was carried out using the method Functional observational battery. The experimental animals as well as controls were observed at 24 hours and 7 days following tabun or saline administration. 3. The results were compared to the condition of animals without anticholinergic drug (oxime alone) and control rats that received physiological solution instead of tabun and treatment. Antidotal treatment involving centrally acting anticholinergic drugs (benactyzine, biperiden, scopolamine) showed significantly higher neuroprotective efficacy compared to antidotal treatment containing atropine.


2015 ◽  
Vol 58 (4) ◽  
pp. 135-143
Author(s):  
Jiří Kassa ◽  
Jana Hatlapatková ◽  
Jana Žďárová Karasová

Aim: The ability of two newly developed oximes (K727, K733) to reduce tabun-induced acute neurotoxic signs and symptoms was evaluated and compared with currently available trimedoxime in rats. Methods: The neuroprotective effects of the oximes studied combined with atropine on Wistar rats poisoned with tabun at a lethal dose (380 µg/kg i.m.; 90% of LD50 value) were evaluated. Tabun-induced neurotoxicity was monitored by the functional observational battery consisting of 38 measurements of sensory, motor and autonomic nervous functions at 2 hours following tabun challenge. Results: All tested oximes combined with atropine enable tabun-poisoned rats to survive till the end of experiment. Both newly developed oximes (K727, K733) combined with atropine were able to decrease tabun-induced neurotoxicity in the case of lethal poisoning although they did not eliminate all tabun-induced acute neurotoxic signs and symptoms. Conclusion: The ability of both novel bispyridinium oximes to decrease tabun-induced acute neurotoxicity was slightly lower than that of trimedoxime. Therefore, the newly developed oximes are not suitable for the replacement of commonly used oximes such as trimedoxime in the treatment of acute tabun poisonings.


1983 ◽  
Vol 61 (6) ◽  
pp. 649-652 ◽  
Author(s):  
G. Labrecquf ◽  
P. M. Bélanger ◽  
F. M. Doré

Temporal variations in the anti-inflammatory action and in the ulcerogenic and lethal effects of phenylbutazone were studied in rats. The results indicate that small doses of the drug produced a larger reduction of paw edema in the morning than in the evening. At 0900, doses of 10, 30, and 100 mg/kg of phenylbutazone reduced the carrageenan-induced paw edema by 23, 44, and 66%, respectively. At 2000, the same doses of the drug decreased the paw edema by 9, 22, and 62%, respectively. No circadian variation was observed in the ulcerogenic effect of phenylbutazone. The mean lethal dose (LD50) of the drug was larger in the morning than in the evening and the values obtained were 710 ± 24 (SE) mg/kg at 0900 in comparison to 525 ± 38 (SE) mg/kg at 2000.


1942 ◽  
Vol 6a (1) ◽  
pp. 63-73 ◽  
Author(s):  
H. L. A. Tarr ◽  
N. M. Carter

Incorporation of sodium nitrite in the diet of cats and white rats on the basis of an average sized man consuming 1 lb. (454 g.) of fish containing 0.2 per cent (908 mg.) of this salt daily for six days each week does not appear to affect their growth rate nor the development (weight) of their thyroid, heart, lungs, spleen, liver, kidneys or adrenals. The fecundity of white rats as judged by their ability to breed and raise normal litters is apparently not affected thereby. The lethal dose of sodium nitrite by oral route is about 1.1 to 2.0 g./kg. for healthy male rats, 0.46 to 1.2 g./kg. for healthy female rats and 0.073 g./kg. for cats (one animal). The lethal dose by subcutaneous route is about 0.19 to 0.20 g./kg. for healthy male rats and 0.057 to 0.13 g./kg. for healthy female rats.


PEDIATRICS ◽  
1974 ◽  
Vol 54 (6) ◽  
pp. 689-695
Author(s):  
Robert M. Shuman ◽  
Richard W. Leech ◽  
Ellsworth C. Alvord

To assess the susceptibility of human beings to the neurotoxic effects of hexachlorophene demonstrated in experimental animals, a blind clinicopathologic analysis was made of 248 children coming to autopsy over a 7.5-year period in the two Seattle institutions to which practically all premature or sick children are referred. Repeated whole-body bathing of premature newborn infants in 3% hexachlorophene-bearing soap (undiluted pHisoHex) is associated with a vacuolar encephalopathy of the brainstem reticular formation. The prevalence of the vacuolar encephalopathy appears to be related to the number of exposures to hexachlorophene, to the concentration of hexachiorophene, to the birth weight (gestational age), to the length of survival and to the thoroughness of rinsing. From these observations we conclude that hexachlorophene should not be used on neonates under 1,400 gm birth weight and should be used only sparingly in full-term neonates with thorough rinsing.


2014 ◽  
Vol 31 (02) ◽  
pp. 123-127 ◽  
Author(s):  
S. Gupta ◽  
S. Kalra ◽  
V. Bharihoke ◽  
D. Dhurandhar

AbstractIn the present world people have become conscious of the fact that sugar is one of the commonest culprits for gain in weight and blood sugar in diabetes. One of the artificial sweetener, sucralose is widely used by diabetics is still under strict scrutiny because of the contradictory feedbacks obtained from various studies, often discouraging its use. Therefore, there arises a need to check whether the use of sucralose is safe or not. The present study was designed to determine to evaluate and compare the histological changes of sucralose on the islets of pancreas in albino rats. Methods: The adult Wistar albino rats were given sucralose orally by gavage in the dose of 3gms/kg body weight/day dissolved in distilled water and only distilled water for 30 days to experimental and control groups respectively. The animals were weighed prior to and after the experiment. The animals were sacrificed on day 31. The pancreas was dissected and observed grossly. Tissue was processed; paraffin blocks were prepared and 8 micron thick sections were cut. Sections were stained with Haemotoxylin and Eosin and Gomori's stains. Results: Pancreatic toxicity was observed in the form of vaculation of islets, lymphocytic infilterate, degeneration of islets and acini of Pancreas. The commonly used non-lethal dose of sucralose induced damage to Pancreas is startling. Conclusion: The results obtained have wide implications for nutrient sensing and nutrition in the treatment of obesity and diabetes.


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