engleski

An insight in tabun toxicity through the measurement of biomarkers of oxidative stress in blood and brain of exposed rats

It is generally known that irreversible inhibition of acetylcholinesterase (AChE) by organophosphorous (OP) agents causes the vast majority of symptoms associated with their acute toxicity. Even if their acute effects exhibiting cholinergic disturbances have been extensively described, questions about their effects on molecular level following both acute and chronic exposure remain largely unanswered. Studies in experimental animals and tissue cultures, as well as in acutely or chronically exposed humans, have implicated a strong linkage between OP pesticide poisoning and the induction of oxidative stress. Since we have no such knowledge on OP nerve agents, the present study was conducted to analyze the biomarkers of oxidative damage to lipids, proteins and DNA in the tissue samples of tabun poisoned rats. Temporal and spatial distribution of the AChE activity in blood and brain of rats exposed to sublethal dose of tabun (75 % of its LD50) was determined by the Ellman assay. We used lipid peroxidation (LPO), activity of superoxide dismutase (SOD) and primary DNA damage determined by comet assay as markers of oxidative stress. The strong inhibitory effect (~90 %) of tabun was observed in the plasma during the first hour of exposition while the highest degree of inhibition (75 %) in the brain as a target organ was observed 1 h after tabun exposure, which is consistent with the culmination of the symptoms of poisoning. Enzyme activity in plasma and brain even 24 h after a single exposure to tabun did not fully recovered. Increased LPO was observed in plasma up to 6 h after tabun exposure, whereas increased level of primary DNA damage, activity of SOD and LPO were noticed in the brain during 24 h exposure to tabun. These results indicate that tabun poisoning caused excessive formation of free radicals which could associate oxidative stress with the neurotoxicity of tabun. Further understanding on how oxidative stress may be mediating toxicity of nerve agents can contribute in designing new and more efficient therapeutic strategies.

Tabun; Oxidative stress; Plasma; Brain

nije evidentirano