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

Miroslav Pohanka, Jakub Sobotka, Hana Svobodova, Rudolf Stetina

Index: Drug Chem. Toxicol. 34(3) , 255-60, (2011)

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Abstract

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.