scholarly journals A Comparison of the Potency of Newly Developed Oximes (K347, K628) and Currently Available Oximes (Obidoxime, HI-6) to Counteract Acute Neurotoxic Effects of Tabun in Rats

2010 ◽  
Vol 53 (2) ◽  
pp. 85-91
Author(s):  
Jiří Kassa ◽  
Jana Žďárová Karasová ◽  
Sandra Tesařová ◽  
Kamil Musílek ◽  
Kamil Kuča
Keyword(s):  
Motor Activity ◽  
Automatic Measurement ◽  
Signs And Symptoms ◽  
Sublethal Dose ◽  
Neuroprotective Effects ◽  
Hi 6 ◽  
Neurotoxic Effects ◽  
Acute Neurotoxicity ◽  
Neuroprotective Efficacy ◽  
Functional Observational Battery

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.

scholarly journals Neuroprotective Effects of Antidotes in Soman-Poisoned Rats

1999 ◽  
Vol 42 (4) ◽  
pp. 127-131 ◽  
Author(s):  
Jiří Kassa ◽  
Marie Koupilová
Keyword(s):  
Motor Activity ◽  
Automatic Measurement ◽  
Nerve Agents ◽  
The Other ◽  
Sublethal Dose ◽  
Neuroprotective Effects ◽  
Hi 6 ◽  
Other Hand ◽  
Functional Observational Battery

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.

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
Keyword(s):  
Motor Activity ◽  
Lethal Dose ◽  
Automatic Measurement ◽  
Albino Rats ◽  
Lethal Effects ◽  
Experimental Animals ◽  
Hi 6 ◽  
Neurotoxic Effects ◽  
Neuroprotective Efficacy ◽  
Functional Observational Battery

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.

scholarly journals A Comparison of the Neuroprotective Efficacy of Newly Developed Oximes (K156, K203) and Currently Available Oximes (Obidoxime, HI-6) in Cyclosarin-poisoned Rats

2008 ◽  
Vol 51 (4) ◽  
pp. 215-221 ◽  
Author(s):  
Jiří Kassa ◽  
Jana Žďárová Karasová ◽  
Sandra Tesařová ◽  
Kamil Kuča ◽  
Kamil Musílek
Keyword(s):  
Signs And Symptoms ◽  
Neuroprotective Effects ◽  
Hi 6 ◽  
Neuroprotective Efficacy ◽  
Functional Observational Battery

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.

scholarly journals A Comparison of the Neuroprotective and Reactivating Efficacy of a Novel Bispyridinium Oxime K870 with Commonly Used Pralidoxime and the Oxime HI-6 in Tabun-Poisoned Rats

2021 ◽  
Vol 64 (3) ◽  
pp. 145-152
Author(s):  
Jiří Kassa ◽  
Jana Hatlapatková ◽  
Jana Žďárová Karasová ◽  
Vendula Hepnarová ◽  
Filip Caisberger ◽  
...  
Keyword(s):  
Brain Damage ◽  
Acetylcholinesterase Activity ◽  
Sublethal Dose ◽  
Neuroprotective Effects ◽  
Hi 6 ◽  
Histopathological Evaluation ◽  
Acute Neurotoxicity ◽  
Neuroprotective Efficacy ◽  
The Brain

Aim: The comparison of neuroprotective and central reactivating effects of the oxime K870 in combination with atropine with the efficacy of standard antidotal treatment in tabun-poisoned rats. Methods: The neuroprotective effects of antidotal treatment were determined in rats poisoned with tabun at a sublethal dose using a functional observational battery 2 h and 24 h after tabun administration, the tabun-induced brain damage was investigated by the histopathological evaluation and central reactivating effects of oximes was evaluated by the determination of acetylcholinesterase activity in the brain using a standard spectrophotometric method. Results: The central reactivating efficacy of a newly developed oxime K870 roughly corresponds to the central reactivating efficacy of pralidoxime while the ability of the oxime HI-6 to reactivate tabun-inhibited acetylcholinesterase in the brain was negligible. The ability of the oxime K870 to decrease tabun-induced acute neurotoxicity was slightly higher than that of pralidoxime and similar to the oxime HI-6. These results roughly correspond to the histopathological evaluation of tabun-induced brain damage. Conclusion: The newly synthesized oxime K870 is not a suitable replacement for commonly used oximes in the antidotal treatment of acute tabun poisonings because its neuroprotective efficacy is only slightly higher or similar compared to studied currently used oximes.

scholarly journals The Evaluation of the Potency of Newly Developed Oximes (K727, K733) and Trimedoxime to Counteract Acute Neurotoxic Effects of Tabun in Rats

2015 ◽  
Vol 58 (4) ◽  
pp. 135-143
Author(s):  
Jiří Kassa ◽  
Jana Hatlapatková ◽  
Jana Žďárová Karasová
Keyword(s):  
Wistar Rats ◽  
Lethal Dose ◽  
Signs And Symptoms ◽  
Neuroprotective Effects ◽  
Autonomic Nervous ◽  
Sensory Motor ◽  
Neurotoxic Effects ◽  
Acute Neurotoxicity ◽  
Functional Observational Battery

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.

scholarly journals Colistin Induced Neurotoxicity in a Patient with End Stage Kidney Disease and Recovery with Conventional Hemodialysis

2015 ◽  
Vol 8 (1) ◽  
pp. 53-55 ◽  
Author(s):  
Radhika Chemmangattu Radhakrishnan ◽  
Shibu Jacob ◽  
Harish Ratnakarrao Pathak ◽  
Veerasami Tamilarasi
Keyword(s):  
Bacterial Infections ◽  
Blood Stream Infection ◽  
Signs And Symptoms ◽  
Blood Stream ◽  
Multidrug Resistant ◽  
End Stage Kidney Disease ◽  
Neurotoxic Effects ◽  
Stage Renal Disease ◽  
End Stage ◽  
Conventional Hemodialysis

Colistin is widely used in the treatment of multidrug resistant bacterial infections. Nephrotoxicity and neurotoxicity are risks associated with colistin use. We report the case of a 50 year old lady with end stage renal disease, treated with colistin for catheter related blood stream infection and developed muscle weakness and parasthesia. Concomitant use of meropenem may have precipitated neurotoxicity of colistin. Conventional hemodialysis was effective in reversing her signs and symptoms. Clinicians should be aware of the risk of neurotoxicity while using colistin, especially after a loading dose in patients with renal impairment. According to our knowledge, this is the first report of conventional hemodialysis reversing the neurotoxic effects of colistin.

scholarly journals Toxicity associated with ingestion of a polyacrylic acid hydrogel dog pad

2018 ◽  
Vol 30 (5) ◽  
pp. 708-714 ◽  
Author(s):  
David C. Dorman ◽  
Melanie L. Foster ◽  
Brooke Olesnevich ◽  
Brad Bolon ◽  
Aude Castel ◽  
...  
Keyword(s):  
Motor Activity ◽  
Polyacrylic Acid ◽  
Muscle Tone ◽  
Clinical Signs ◽  
High Dose ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Before And After ◽  
Acute Neurotoxicity ◽  
Disposable Diapers

Superabsorbent sodium polyacrylate polymeric hydrogels that retain large amounts of liquids are used in disposable diapers, sanitary napkins, and other applications. These polymers are generally considered “nontoxic” with acute oral median lethal doses (LD50) >5 g/kg. Despite this favorable toxicity profile, we identified a novel toxic syndrome in dogs and rats following the ingestion of a commercial dog pad composed primarily of a polyacrylic acid hydrogel. Inappropriate mentation, cerebellar ataxia, vomiting, and intention tremors were observed within 24 h after the ingestion of up to 15.7 g/kg of the hydrogel by an adult, castrated male Australian Shepherd mix. These observations prompted an experimental study in rats to further characterize the toxicity of the hydrogel. Adult, female Sprague Dawley rats ( n = 9) were assessed before and after hydrogel ingestion (2.6–19.2 g/kg over 4 h) using a functional observation battery and spontaneous motor activity. Clinical signs consistent with neurotoxicity emerged in rats as early as 2 h after the end of hydrogel exposure, including decreased activity in an open field, hunched posture, gait changes, reduced reaction to handling, decreased muscle tone, and abnormal surface righting. Hydrogel-exposed rats also had reduced motor activity when compared with pre-exposure baseline data. Rats that ingested the hydrogel did not develop nervous system lesions. These findings support the conclusion that some pet pad hydrogel products can induce acute neurotoxicity in animals under high-dose exposure conditions.

scholarly journals A Topical Formulation of Melatoninergic Compounds Exerts Strong Hypotensive and Neuroprotective Effects in a Rat Model of Hypertensive Glaucoma

2020 ◽  
Vol 21 (23) ◽  
pp. 9267
Author(s):  
Massimo Dal Monte ◽  
Maurizio Cammalleri ◽  
Rosario Amato ◽  
Salvatore Pezzino ◽  
Roberta Corsaro ◽  
...  
Keyword(s):  
Rat Model ◽  
Ganglion Cells ◽  
Hypotensive Activity ◽  
Retinal Ganglion ◽  
Topical Formulation ◽  
Adrenergic Agonist ◽  
Neuroprotective Effects ◽  
Neuroprotective Efficacy ◽  
Iop Elevation ◽  
Ocular Health

Melatonin is of great importance for regulating several eye processes, including pressure homeostasis. Melatonin in combination with agomelatine has been recently reported to reduce intraocular pressure (IOP) with higher efficacy than each compound alone. Here, we used the methylcellulose (MCE) rat model of hypertensive glaucoma, an optic neuropathy characterized by the apoptotic death of retinal ganglion cells (RGCs), to evaluate the hypotensive and neuroprotective efficacy of an eye drop nanomicellar formulation containing melatonin/agomelatine. Eye tissue distribution of melatonin/agomelatine in healthy rats was evaluated by HPLC/MS/MS. In the MCE model, we assessed by tonometry the hypotensive efficacy of melatonin/agomelatine. Neuroprotection was revealed by electroretinography; by levels of inflammatory and apoptotic markers; and by RGC density. The effects of melatonin/agomelatine were compared with those of timolol (a beta blocker with prevalent hypotensive activity) or brimonidine (an alpha 2 adrenergic agonist with potential neuroprotective efficacy), two drugs commonly used to treat glaucoma. Both melatonin and agomelatine penetrate the posterior segment of the eye. In the MCE model, IOP elevation was drastically reduced by melatonin/agomelatine with higher efficacy than that of timolol or brimonidine. Concomitantly, gliosis-related inflammation and the Bax-associated apoptosis were partially prevented, thus leading to RGC survival and recovered retinal dysfunction. We suggest that topical melatoninergic compounds might be beneficial for ocular health.

An Estrogen Replacement Therapy Containing Nine Synthetic Plant-Based Conjugated Estrogens Promotes Neuronal Survival

2003 ◽  
Vol 228 (7) ◽  
pp. 823-835 ◽  
Author(s):  
Lixia Zhao ◽  
Shuhua Chen ◽  
Roberta D. Brinton
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Replacement Therapy ◽  
Estrogen Replacement Therapy ◽  
Neuronal Survival ◽  
Estrogen Replacement ◽  
Neuroprotective Effects ◽  
Conjugated Estrogens ◽  
Neuroprotective Efficacy

Epidemiological data from retrospective and case–control studies have indicated that estrogen replacement therapy can decrease the risk of developing Alzheimer’s disease. In addition, estrogen replacement therapy has been found to promote neuronal survival both in vivo and in vitro. We have shown that conjugated equine estrogens (CEE), containing 238 different molecules composed of estrogens, progestins, and androgens, exerted neurotrophic and neuroprotective effects in cultured neurons. In the current study, we sought to determine whether a steroidal formulation of nine synthetic conjugated estrogens (SCE) chemically derived from soybean and yam extracts is as effective as the complex multisteroidal formulation of CEE. Analyses of the neuroprotective efficacy indicate that SCE exhibited significant neuroprotection against beta amyloid, hydrogen peroxide, and glutamate-induced toxicity in cultured hippocampal neurons. Indices of neuroprotection included an increase in neuronal survival, a decrease in neurotoxin-induced lactate dehydrogenase release, and a reduction in neurotoxin-induced apoptotic cell death. Furthermore, SCE was found to attenuate excitotoxic glutamate-induced [Ca2+]i rise. Quantitative analyses indicate that the neuroprotective efficacy of SCE was comparable to that of the multisteroidal CEE formulation. Data derived from these investigations predict that SCE could exert neuroprotective effects comparable to CEE in vivo and therefore could reduce the risk of Alzheimer’s disease in postmenopausal women.

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