Effect of six oximes on acutely anticholinesterase inhibitor-induced oxidative stress in rat plasma and brain
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2018
Authors
Antonijević, Evica
Kotur-Stevuljević, Jelena

Musilek, Kamil

Kosvancova, Andrea
Kuca, Kamil

Đukić-Ćosić, Danijela

Spasojević-Kalimanovska, Vesna

Antonijević, Biljana

Article (Published version)

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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 (O-2 (center dot-)) and total oxidative status (TOS); antioxidative-superoxide dismutase (SOD), total thiol (SH) groups, total antioxidant status (TAS) and paraoxonase (PON1); tissue oxida...tive 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.
Keywords:
Pro-oxidants / Antioxidats / Oxime K027 / Oxime K203 / Dichlorvos / EfficacySource:
Archives of Toxicology, 2018, 92, 2, 745-757Publisher:
- Springer Heidelberg, Heidelberg
Funding / projects:
DOI: 10.1007/s00204-017-2101-z
ISSN: 0340-5761
PubMed: 29098328
WoS: 000425526000016
Scopus: 2-s2.0-85032950416
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PharmacyTY - JOUR AU - Antonijević, Evica AU - Kotur-Stevuljević, Jelena AU - Musilek, Kamil AU - Kosvancova, Andrea AU - Kuca, Kamil AU - Đukić-Ćosić, Danijela AU - Spasojević-Kalimanovska, Vesna AU - Antonijević, Biljana PY - 2018 UR - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3170 AB - 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 (O-2 (center dot-)) 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. PB - Springer Heidelberg, Heidelberg T2 - Archives of Toxicology T1 - Effect of six oximes on acutely anticholinesterase inhibitor-induced oxidative stress in rat plasma and brain VL - 92 IS - 2 SP - 745 EP - 757 DO - 10.1007/s00204-017-2101-z ER -
@article{ author = "Antonijević, Evica and Kotur-Stevuljević, Jelena and Musilek, Kamil and Kosvancova, Andrea and Kuca, Kamil and Đukić-Ćosić, Danijela and Spasojević-Kalimanovska, Vesna and Antonijević, Biljana", year = "2018", abstract = "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 (O-2 (center dot-)) 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.", publisher = "Springer Heidelberg, Heidelberg", journal = "Archives of Toxicology", title = "Effect of six oximes on acutely anticholinesterase inhibitor-induced oxidative stress in rat plasma and brain", volume = "92", number = "2", pages = "745-757", doi = "10.1007/s00204-017-2101-z" }
Antonijević, E., Kotur-Stevuljević, J., Musilek, K., Kosvancova, A., Kuca, K., Đukić-Ćosić, D., Spasojević-Kalimanovska, V.,& Antonijević, B.. (2018). Effect of six oximes on acutely anticholinesterase inhibitor-induced oxidative stress in rat plasma and brain. in Archives of Toxicology Springer Heidelberg, Heidelberg., 92(2), 745-757. https://doi.org/10.1007/s00204-017-2101-z
Antonijević E, Kotur-Stevuljević J, Musilek K, Kosvancova A, Kuca K, Đukić-Ćosić D, Spasojević-Kalimanovska V, Antonijević B. Effect of six oximes on acutely anticholinesterase inhibitor-induced oxidative stress in rat plasma and brain. in Archives of Toxicology. 2018;92(2):745-757. doi:10.1007/s00204-017-2101-z .
Antonijević, Evica, Kotur-Stevuljević, Jelena, Musilek, Kamil, Kosvancova, Andrea, Kuca, Kamil, Đukić-Ćosić, Danijela, Spasojević-Kalimanovska, Vesna, Antonijević, Biljana, "Effect of six oximes on acutely anticholinesterase inhibitor-induced oxidative stress in rat plasma and brain" in Archives of Toxicology, 92, no. 2 (2018):745-757, https://doi.org/10.1007/s00204-017-2101-z . .