Toxic Injury to Muscle Tissue of Rats Following Acute Oximes Exposure

Jacević, Vesna; Nepovimová, Eugenie; Kuča, Kamil

doi:10.1038/s41598-018-37837-4

Cited by 19 publications

(17 citation statements)

References 72 publications

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“…As found in the literature, it was confirmed that all reactivators tested at high dosages caused damage to both visceral tissues and the overall health of the individual. The data obtained may be an important support for dose choices regarding different reactivators structures for newly developed drugs [71,72].…”

Section: Ache Reactivation Processesmentioning

confidence: 84%

Trends in the Recent Patent Literature on Cholinesterase Reactivators (2016–2019)

et al. 2020

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Acetylcholinesterase (AChE) is the key enzyme responsible for deactivating the ACh neurotransmitter. Irreversible or prolonged inhibition of AChE, therefore, elevates synaptic ACh leading to serious central and peripheral adverse effects which fall under the cholinergic syndrome spectra. To combat the toxic effects of some AChEI, such as organophosphorus (OP) nerve agents, many compounds with reactivator effects have been developed. Within the most outstanding reactivators, the substances denominated oximes stand out, showing good performance for reactivating AChE and restoring the normal synaptic acetylcholine (ACh) levels. This review was developed with the purpose of covering the new advances in AChE reactivation. Over the past years, researchers worldwide have made efforts to identify and develop novel active molecules. These researches have been moving farther into the search for novel agents that possess better effectiveness of reactivation and broad-spectrum reactivation against diverse OP agents. In addition, the discovery of ways to restore AChE in the aged form is also of great importance. This review will allow us to evaluate the major advances made in the discovery of new acetylcholinesterase reactivators by reviewing all patents published between 2016 and 2019. This is an important step in continuing this remarkable research so that new studies can begin.

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Section: Ache Reactivation Processesmentioning

confidence: 84%

Trends in the Recent Patent Literature on Cholinesterase Reactivators (2016–2019)

et al. 2020

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“…Our previous study has confirmed that exposure to low, injury-free oxime concentration, which was unable to cause muscle cells’ damage. Further increase in their doses leads to different muscular tissue damages due to their potent cytotoxic and pro-inflammatory effect 25 . Several investigators confirmed this statement in vitro 18,19 , but not so far in vivo 18,19 .…”

Section: Discussionmentioning

confidence: 99%

“…Since all the toxicological data were provided in the earlier studies 25,26 , in this third study, we focused our attention on an investigation of morphological lesions of visceral tissue’s produced by increasing doses of selected AChE reactivators. For this purpose, standard oximes (i.e.…”

Section: Introductionmentioning

confidence: 99%

Acute Toxic Injuries of Rat’s Visceral Tissues Induced by Different Oximes

Jacević

Nepovimová

Kuča

2019

Sci Rep

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Certain AChE reactivators, asoxime, obidoxime, K027, K048, and K075, when taken in overdoses and sometimes even when introduced within therapeutic ranges, may injure the different organs. As a continuation of previously published data, in this study, Wistar rats have sacrificed 24 hrs and 7 days after single im application of 0.1LD50, 0.5LD50 and 1.0LD50 of each reactivator, and examinated tissue samples were obtained for pathohistological and semiquantitative analysis. A severity of tissue alteration, expressed as different tissue damage scores were evaluated. Morphological structure of examinated tissues treated with of 0.1LD50 of all reactivators was comparable with the control group of rats. Moderate injuries were seen in visceral tissues treated with 0.5LD50 of asoxime, obidoxime and K027. Acute damages were enlarged after treatment with 0.5LD50 and 1.0LD50 of all reactivators during the next 7 days. The most prominent changes were seen in rats treated with 1.0LD50 of K048 and K075 (P < 0.001 vs. control and asoxime-treated group). All reactivators given by a single, high, unitary dose regimen, have an adverse effect not only on the main visceral tissue, but on the whole rat as well, but the exact mechanism of cellular injury remains to be confirmed in further investigation.

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“…Each 2-μm thick paraffin section was stained with hematoxylin and eosin (H&E), and exanimated at a magnification of 200× using a light microscope (BKS-45, Olympus, Japan), according to our previously published methodology [ 9 , 17 , 18 , 19 , 20 , 71 , 72 , 73 , 74 , 75 , 76 , 77 ].…”

Section: Methodsmentioning

confidence: 99%

Antidotal Potency of the Novel, Structurally Different Adsorbents in Rats Acutely Intoxicated with the T-2 Toxin

Jacević

Dumanović

Lazarević

et al. 2020

Toxins

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In this paper, the potential antidote efficacy of commercially available formulations of various feed additives such as Minazel-Plus®, Mycosorb®, and Mycofix® was considered by recording their incidence on general health, body weight, and food and water intake, as well as through histopathology and semiquantitative analysis of gastric alterations in Wistar rats treated with the T-2 toxin in a single-dose regimen of 1.67 mg/kg p.o. (1 LD50) for 4 weeks. As an organic adsorbent, Mycosorb® successfully antagonized acute lethal incidence of the T-2 toxin (protective index (PI) = 2.25; p < 0.05 vs. T-2 toxin), and had adverse effects on body weight gain as well as food and water intake during the research (p < 0.001). However, the protective efficacy of the other two food additives was significantly lower (p < 0.05). Treatment with Mycosorb® significantly reduced the severity of gastric damage, which was not the case when the other two adsorbents were used. Our results suggest that Mycosorb® is a much better adsorbent for preventing the adverse impact of the T-2 toxin as well as its toxic metabolites compared with Minazel-plus® or Mycofix-plus®, and it almost completely suppresses its acute toxic effects and cytotoxic potential on the gastric epithelial, glandular, and vascular endothelial cells.

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Toxic Injury to Muscle Tissue of Rats Following Acute Oximes Exposure

Cited by 19 publications

References 72 publications

Trends in the Recent Patent Literature on Cholinesterase Reactivators (2016–2019)

Trends in the Recent Patent Literature on Cholinesterase Reactivators (2016–2019)

Acute Toxic Injuries of Rat’s Visceral Tissues Induced by Different Oximes

Antidotal Potency of the Novel, Structurally Different Adsorbents in Rats Acutely Intoxicated with the T-2 Toxin

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