Modulation of Tularemia Disease Progress by the Bisquaternary Pyridinium Oxime HI-6

Pohanka, Miroslav; Pavliš, Oto; Pikula, Jiří; Treml, F.; Kuča, Kamil

doi:10.2754/avb201079030443

Cited by 4 publications

(2 citation statements)

References 17 publications

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“…Recently, HI-6 was recognized as an immunomodulatory compound, significantly modifying the progression of infection and disease represented by tularemia (Pohanka et al, 2010). Vrdoljak et al (2009) found that HI-6 relieves to suppress the side effects of topoisomerase 1 inhibitor irinotecan, which is approved for cancer treatment.…”

Section: Discussionmentioning

confidence: 99%

Investigation of oxidative stress in blood, brain, kidney, and liver after oxime antidote HI-6 application in a mouse experimental model

Pohanka

Sobotka

Svobodová

et al. 2011

Drug and Chemical Toxicology

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Oxime reactivator HI-6 (asoxime, in some sources) is a potent antidote suitable for treatment of intoxication by nerve agents. Despite the fact that HI-6 is considered for practical application in emergency situations, the impact of HI-6 on patients' bodies has not been established yet. The present experiment was carried out in order to estimate whether HI-6 would be able to trigger or protect from oxidative stress in a BALB/c mice model. HI-6 was applied in doses ranging from 0.2 to 20% of LD₅₀. Ferric-reducing antioxidant power (FRAP), thiobarbituric acid reactive substances (TBARS), reduced glutathione (GSH), and glutathione reductase (GR) were assayed in the blood, liver, kidney, and brain of treated animals. It was found that HI-6 does not increase GR or TBARS. On the contrary, TBARS levels in the brain and liver were found to be significantly decreased in HI-6-treated animals. Pertinent antioxidant properties of HI-6 were excluded by the FRAP method. Endogenous antioxidants were unchanged, with the exception of the kidney. Low-molecular-weight antioxidants assayed by the FRAP method were significantly decreased in kidneys of animals treated with HI-6. However, GSH partially recovered the loss of the other low-molecular-weight antioxidants and was significantly increased in the kidney of HI-6-exposed mice. HI-6 potential to produce nephropathy is hypothesized. The achieved conclusions were quite surprising and showed a complex impact of HI-6 on the body.

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Section: Discussionmentioning

confidence: 99%

Investigation of oxidative stress in blood, brain, kidney, and liver after oxime antidote HI-6 application in a mouse experimental model

Pohanka

Sobotka

Svobodová

et al. 2011

Drug and Chemical Toxicology

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“…It was proved that these compounds can bind like acetylcholine due to the quarternary ammonium atom and interact with AChE and with AChR [ 86 , 87 ]. Biological effects HI-6 (asoxime; Figure 3 ) are considered to be associated with α7 nAChR; unfortunately the plausible proof is still missing [ 88 , 89 ]. The antagonists of α7 nAChR are summarized in Table 1 .…”

Section: Antagonists Of α7 Nachrmentioning

confidence: 99%

Alpha7 Nicotinic Acetylcholine Receptor Is a Target in Pharmacology and Toxicology

Pohanka

2012

IJMS

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152

106

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Alpha7 nicotinic acetylcholine receptor (α7 nAChR) is an important part of the cholinergic nerve system in the brain. Moreover, it is associated with a cholinergic anti-inflammatory pathway in the termination of the parasympathetic nervous system. Antagonists of α7 nAChR are a wide group represented by conotoxin and bungarotoxin. Even Alzheimer’s disease drug memantine acting as an antagonist in its side pathway belongs in this group. Agonists of α7 nAChR are suitable for treatment of multiple cognitive dysfunctions such as Alzheimer’s disease or schizophrenia. Inflammation or even sepsis can be ameliorated by the agonistic acting compounds. Preparations RG3487, SEN34625/WYE-103914, SEN12333, ABT-107, Clozapine, GTS-21, CNI-1493, and AR-R17779 are representative examples of the novel compounds with affinity toward the α7 nAChR. Pharmacological, toxicological, and medicinal significance of α7 nAChR are discussed throughout this paper.

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Asoxime (HI-6) impact on dogs after one and tenfold therapeutic doses: Assessment of adverse effects, distribution, and oxidative stress

Pohanka

Novotný

Karasová

et al. 2011

Environmental Toxicology and Pharmacology

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Modulation of Tularemia Disease Progress by the Bisquaternary Pyridinium Oxime HI-6

Cited by 4 publications

References 17 publications

Investigation of oxidative stress in blood, brain, kidney, and liver after oxime antidote HI-6 application in a mouse experimental model

Investigation of oxidative stress in blood, brain, kidney, and liver after oxime antidote HI-6 application in a mouse experimental model

Alpha7 Nicotinic Acetylcholine Receptor Is a Target in Pharmacology and Toxicology

Asoxime (HI-6) impact on dogs after one and tenfold therapeutic doses: Assessment of adverse effects, distribution, and oxidative stress

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