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.
Highlights
Nerve agents and organophosphorus pesticides are organic compounds obtained from phosphorus and characterized by a high toxicity to mammals
Ferric reducing antioxidant power (FRAP) was used for the assessment of antioxidants content (Tables 1 and 2), lipid peroxidation was represented by thiobarbituric acid reactive substances (TBARS) (Tables 3 and 4) and enzymatic marker by glutathione reductase (GR) (Tables 5 and 6)
Our results indicated that the level of low molecular weight antioxidants decreased in all the organs after administration of obidoxime with the exception of kidneys
Summary
Nerve agents and organophosphorus pesticides are organic compounds obtained from phosphorus and characterized by a high toxicity to mammals. Acute organophosphorus pesticide poisoning causes tens of thousands of deaths each year across the developing world (Buckley et al, 2011). Their main toxic effect is inhibition of enzyme acetylcholinesterase (AChE; EC 3.1.1.7); the phosphorous substances covalently bind to hydroxyl group of serine molecule in catalytic site of AChE. The therapy after organophosphorus poisoning is symptommatic (atropine and/or anticonvulsants) and causative (oxime reactivators). Oximes react with nerve agents and pesticides bind the AChE active site (Pohanka, 2011). Oxidative stress is an imbalance between formation and removal of reactive oxygen species. Oxidative stress in humans results in many diseases - including the neuro-degenerative ones such as Parkinsons disease, Alzheimers disease, and Huntington’s disease (Guglielmotto et al, 2010); cardiovascular disease – myocardial infarction, atherosclerosis, heart failure (Ramond et al, 2011); and others – fragile X syndrome or chronic fatigue syndrome (Kennedy et al, 2005)
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
