Effect of six oximes on acutely anticholinesterase inhibitor-induced oxidative stress in rat plasma and brain
Language English Country Germany Media print-electronic
Document type Journal Article
Grant support
Project No. III46009
Ministry of Education, Science and Technological Development of the Republic of Serbia
OI 175035
Ministry of Education, Science and Technological Development of the Republic of Serbia
No. 2110
Specific Research Project of Faculty of Science, University of Hradec Kralove
2016
Specific Research Project of Faculty of Science, University of Hradec Kralove
8F17004
Ministry of Education, Youth and Sports
PubMed
29098328
DOI
10.1007/s00204-017-2101-z
PII: 10.1007/s00204-017-2101-z
Knihovny.cz E-resources
- Keywords
- Antioxidats, Dichlorvos, Efficacy, Oxime K027, Oxime K203, Pro-oxidants,
- MeSH
- Aryldialkylphosphatase blood MeSH
- Biomarkers blood MeSH
- Cholinesterase Inhibitors pharmacology MeSH
- Dichlorvos toxicity MeSH
- Rats MeSH
- Malondialdehyde blood MeSH
- Brain drug effects MeSH
- Obidoxime Chloride pharmacology MeSH
- Organophosphate Poisoning drug therapy MeSH
- Oxidative Stress drug effects MeSH
- Oximes pharmacology MeSH
- Pralidoxime Compounds MeSH
- Pyridinium Compounds pharmacology MeSH
- Superoxide Dismutase blood MeSH
- Trimedoxime pharmacology MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Male MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- Aryldialkylphosphatase MeSH
- asoxime chloride MeSH Browser
- Biomarkers MeSH
- Cholinesterase Inhibitors MeSH
- Dichlorvos MeSH
- Malondialdehyde MeSH
- Obidoxime Chloride MeSH
- Oximes MeSH
- Pon1 protein, rat MeSH Browser
- pralidoxime MeSH Browser
- Pralidoxime Compounds MeSH
- Pyridinium Compounds MeSH
- Superoxide Dismutase MeSH
- Trimedoxime MeSH
Beside the key inhibition of acetylcholinesterase (AChE), involvement of oxidative stress in organophosphate (OP)-induced toxicity has been supported by experimental and human studies. On the other hand, according to our best knowledge, possible antioxidant properties of oximes, the only causal antidotes to OP-inhibited AChE, have been examined only by a few studies. Thus, we have determined the effect of four conventional (obidoxime, trimedoxime, pralidoxime, asoxime) and two promising experimental oximes (K027, K203) on dichlorvos (DDVP)-induced oxidative changes in vivo. Wistar rats (5/group) were treated with oxime (5% LD50 i.m) immediately after DDVP challenge (75% LD50 s.c). Oxidative stress biomarkers were determined in plasma and brain 60 min after the treatment: prooxidative-superoxide anion (O2·-) and total oxidative status (TOS); antioxidative-superoxide dismutase (SOD), total thiol (SH) groups, total antioxidant status (TAS) and paraoxonase (PON1); tissue oxidative stress burden-prooxidative-antioxidative balance (PAB) and oxidative stress index (OSI); oxidative tissue damage-malondialdehyde (MDA) and advanced oxidation protein products (AOPP). All oximes were able to attenuate DDVP-induced oxidative stress in rat plasma and brain. Changes of determined parameters in brain were not as prominent as it was seen in plasma. Based on OSI, better abilities of oxime K027, K203 and obidoxime to maintain DDVP-induced oxidative stress in rat brain were shown as compared to trimedoxime, pralidoxime and asoxime. Oximes can influence the complex in vivo redox processes that might contribute to their overall therapeutic efficacy. Further research is needed to understand the underlying molecular mechanisms involved in this phenomenon.
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