Abstract

Obidoxime and asoxime (HI-6) are considered to be the most important acetylcholinesterase (AChE) reactivators applicable for treatment of poisoning by nerve agents. Unfortunately, toxicology of the oximes is not well known. For this reason, we decided to investigate the pertinent adverse effects on guinea pigs which are close to humans in toxicological point of view. HI-6 and obidoxime were administered intramuscularly in 5% of the median lethal dose. The animals were sacrificed 15, 30, 60, 120, and 240 min after exposure, and the brain, liver, spleen and kidneys were collected. Ferric reducing antioxidant power (FRAP), thiobarbituric acid reactive substances (TBARS), glutathione S-transferase (GST) and glutathione reductase (GR) were measured. Results indicated that obidoxime acted on oxidative stress than HI-6. We found evidence of low molecular weight antioxidants depletion after obidoxime administration. On the other hand, TBARS assay showed significant decrease in brain and little increase in spleen and liver. The effect of HI-6 was more striking than the effect of obidoxime. There was a sign of higher metabolism and production of antioxidants in liver because GR was significantly increased after HI-6 exposure, and it is another sign of ongoing oxidative stress. Owing to the achieved results, obidoxime can be considered as a less toxic drug in counteracting oxidative stress despite its higher toxicity.

Key words: Oxidative stress, obidoxime, HI-6, acetylcholinesterase, butyrylcholinesterase.