Oxidative stress status and morphological injuries in the brain of Wistar rats induced by repeated application of selected acetylcholinesterase reactivators - asoxime, obidoxime, K027, K048, K074, and K075 were evaluated. Each oxime in a dose of 0.1 of LD50/kg im was given 2x/week for 4 weeks. Markers of lipid peroxidation (malondialdehyde, MDA), and protein oxidation (advanced oxidation protein products, AOPP), as well as the activity of antioxidant enzymes (catalase, CAT, superoxide dismutase, SOD, glutathione reductase, GR, and glutathione peroxidase, GPx), were estimated in the brain tissue homogenates on day 35 of the study. Brain alterations were carefully quantified by semiquantitative grading scales - brain damage score (BDS). Oxidative stress parameters, MDA and AOPP were significantly highest in the asoxime-, obidoxime- and K075-treated groups (p < 0.001). The activity of SOD and CAT was significantly elevated in the obidoxime-, K048-, and K075-treated groups (p < 0.001). Besides, GR was markedly decreased in the obidoxime- and K074-treated groups (p < 0.01), while treatment with K048, K074 and K075 induced extremely high elevation in GPx levels (p < 0.001). In the same groups of rats, brain alterations associated with polymorphonuclear cell infiltrate were significantly more severe than those observed in animals receiving only asoxime or K027 (p < 0.001). The presented results confirmed that treatment with different oximes significantly improved the oxidative status and attenuated signs of inflammation in rats' brains. Presented results, together with our previously published data can help to predict likely adverse systemic toxic effects, and target organ systems, which are crucial for establishing risk categories, as well as in dose selection of K-oximes as drug candidates.

Centre for Biomedical Research Faculty of Medicine University of Banja Luka Save Mrkalja 14 78000 Banja Luka Bosnia and Herzegovina

Centre for Biomedical Research Faculty of Medicine University of Banja Luka Save Mrkalja 14 78000 Banja Luka Bosnia and Herzegovina; Department of Human Genetics Faculty of Medicine University of Banja Luka Save Mrkalja 14 78000 Banja Luka Bosnia and Herzegovina

Department for Experimental Toxicology and Pharmacology National Poison Control Centre Military Medical Academy Crnotravska 17 11000 Belgrade Serbia; Medical Faculty of the Military Medical Academy University of Defence Crnotravska 17 11000 Belgrade Serbia; Department of Chemistry Faculty of Science University of Hradec Kralove Rokitanskeho 62 500 03 Hradec Kralove Czech Republic

Department of Chemistry Faculty of Science University of Hradec Kralove Rokitanskeho 62 500 03 Hradec Kralove Czech Republic

Department of Chemistry Faculty of Science University of Hradec Kralove Rokitanskeho 62 500 03 Hradec Kralove Czech Republic; Biomedical Research Center University Hospital Hradec Kralove 50005 Hradec Kralove Czech Republic

Department of Pharmacology Toxicology and Clinical Pharmacology Faculty of Medicine University of Banja Luka Save Mrkalja 14 78000 Banja Luka Bosnia and Herzegovina

Medical Faculty of the Military Medical Academy University of Defence Crnotravska 17 11000 Belgrade Serbia; University of Belgrade Faculty of Chemistry Department of Analytical Chemistry Studenski trg 16 11000 Belgrade Serbia

Special Police Unit Ministry of Interior Trebevićka 12 A 11 030 Belgrade Serbia

University of Belgrade Faculty of Pharmacy Department of Pharmaceutical Chemistry Vojvode Stepe 450 11000 Belgrade Serbia

University of Belgrade Institute for Medical Research National Institute of the Republic of Serbia Department for Cardiovascular Research Dr Subotića 4 11 000 Belgrade Serbia

Veterinary Services Center Military Health Department Crnotravska 17 11000 Belgrade Serbia

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