Combined Pre- and Posttreatment of Paraoxon Exposure
Abstract
1. Introduction
2. Results
2.1. Mortalities
2.2. Survival Analysis
3. Discussion
4. Materials and Methods
4.1. Chemicals
4.2. Experimental Animals
4.2.1. Choice of Dosage for Pretreatment
- 2 (pre- and posttreatment) reference groups: only paraoxon exposure.
- Pyridostigmine: 1 µmol/rat = 0.26 mg/rat (= 1 mg/kg average body weight).
- Physostigmine: 0.25 µmol/rat = 0.07 mg/rat (= 0.28 mg/kg average body weight).
- Ranitidine hydrochloride: 12 µmol/rat = 4.21 mg/rat (= 17.0 mg/kg average body weight).
- Tacrine: 4 µmol/rat = 1 mg/rat (= 4.0 mg/kg average body weight).
- K-27: 60 µmol/rat = 26.77 mg/rat (= 108.0 mg/kg average body weight).
4.2.2. Pretreatment, Paraoxon, and Oxime Exposure
4.3. Statistical Analysis
5. Conclusions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Sample Availability: Samples of the compounds K-27 are available from the authors. |
Groups (G) | 30 min | 1 h | 2 h | 3 h | 4 h | 24 h | 48 h |
---|---|---|---|---|---|---|---|
Paraoxon only (pretreatment group) | 63/88/96 | 63/88/96 | 63/88/96 | 67/88/96 | 67/88/96 | 67/88/96 | 67/88/96 |
Paraoxon only (pre- and posttreatment group) | 75/88/92 | 79/88/92 | 79/88/92 | 79/92/92 | 83/92/92 | 83/92/96 | 83/92/96 |
Pyridostigmine pretreatment | 13/88/83 | 21/88/83 | 25/88/88 | 25/88/88 | 25/88/88 | 29/88/88 | 29/88/88 |
Pyridostigmine pretreatment + K-27 posttreatment | 13/100/96 | 13/100/100 | 13/100/100 | 21/100/100 | 21/100/100 | 29/100/100 | 29/100/100 |
Physostigmine pretreatment | 4/29/46 | 4/29/46 | 13/33/46 | 13/33/46 | 13/33/46 | 13/33/46 | 13/33/50 |
Physostigmine pretreatment + K-27 posttreatment | 8/42/54 | 8/42/54 | 8/42/54 | 8/42/54 | 8/42/54 | 8/42/54 | 8/42/54 |
Ranitidine pretreatment | 0/79/92 | 0/83/92 | 4/92/ 92 | 4/92/92 | 8/92/92 | 13/92/92 | 13/92/92 |
Ranitidine pretreatment + K-27 posttreatment | 25/58/83 | 29/67/83 | 33/67/83 | 38/75/83 | 42/83/83 | 46/83/83 | 46/96/83 |
Tacrine pretreatment | 0/54/92 | 0/58/92 | 13/71/92 | 13/79/92 | 13/79/92 | 13/79/92 | 13/79/92 |
Tacrine pretreatment + K-27 posttreatment | 0/63/83 | 0/63/83 | 0/67/83 | 0/71/88 | 0/71/92 | 0/75/92 | 0/79/92 |
K-27 pretreatment | 13/8/13 | 25/17/21 | 25/21/25 | 25/21/29 | 33/29/33 | 46/42/38 | 46/42/42 |
K-27 pretreatment + K-27 posttreatment | 0/25/33 | 17/25/46 | 21/25/46 | 21/29/46 | 21/42/46 | 25/54/50 | 25/58/50 |
Groups | Relative Risk (RR) | 95% CI | p-Value |
---|---|---|---|
Paraoxon-ethyl only | 1 | 1 --- 1 | --- |
Pyridostigmine + paraoxon-ethyl | 0.76 ± 0.13 | 0.54–0.97 | ≤0.05 a |
Pyridostigmine + paraoxon-ethyl+K-27 | 0.91 ± 0.14 | 0.69–1.13 | ≤0.05 |
Physostigmine + paraoxon-ethyl | 0.30 ± 0.15 | 0.06–0.53 | ≤0.05 a,b |
Physostigmine + paraoxon-ethyl+K-27 | 0.32 ± 0.13 | 0.11–0.54 | ≤0.05 a |
Ranitidine + paraoxon-ethyl | 0.72 ± 0.16 | 0.46–0.98 | ≤0.05 a |
Ranitidine + paraoxon-ethyl+K-27 | 0.77 ± 0.10 | 0.61–0.93 | ≤0.05 a |
Tacrine + paraoxon-ethyl | 0.67 ± 0.21 | 0.33–1.00 | ≤0.05 a |
Tacrine + paraoxon-ethyl+K-27 | 0.59 ± 0.12 | 0.41–0.78 | ≤0.05 a |
K-27+ paraoxon-ethyl | 0.34 ± 0.09 | 0.20–0.48 | ≤0.05 a,b |
K-27+ paraoxon-ethyl+K-27 | 0.37 ± 0.08 | 0.24–0.49 | ≤0.05 a |
Molecular Weight | IC50 * [µM] | LD50/LD01 * (µmol/rat) | Injected Dose (≈ ¼ of LD01) (µmol/rat) | Injected Dose (mg/rat) | Injected Dose (mg/kg Average Body Weight ) | |
---|---|---|---|---|---|---|
Pyridostigmine | 261.12 | 0.330 | 7.2/3.7 | 1 | 0.26 | 1 |
Physostigmine (Eserine) | 275.35 | 0.012 | 3.0/0.9 | 0.25 | 0.07 | 0.28 |
Ranitidine | 350.86 | 2.5 | 59/46 | 12 | 4.21 | 17.0 |
Tacrine | 250 | 0.200 | 21.5/16 | 4 | 1 | 4.0 |
K-27 | 446.16 | 414 | 350/250 | 60 | 26.77 | 108.0 |
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Lorke, D.E.; Nurulain, S.M.; Hasan, M.Y.; Kuča, K.; Petroianu, G.A. Combined Pre- and Posttreatment of Paraoxon Exposure. Molecules 2020, 25, 1521. https://doi.org/10.3390/molecules25071521
Lorke DE, Nurulain SM, Hasan MY, Kuča K, Petroianu GA. Combined Pre- and Posttreatment of Paraoxon Exposure. Molecules. 2020; 25(7):1521. https://doi.org/10.3390/molecules25071521
Chicago/Turabian StyleLorke, Dietrich E, Syed M Nurulain, Mohamed Y Hasan, Kamil Kuča, and Georg A Petroianu. 2020. "Combined Pre- and Posttreatment of Paraoxon Exposure" Molecules 25, no. 7: 1521. https://doi.org/10.3390/molecules25071521
APA StyleLorke, D. E., Nurulain, S. M., Hasan, M. Y., Kuča, K., & Petroianu, G. A. (2020). Combined Pre- and Posttreatment of Paraoxon Exposure. Molecules, 25(7), 1521. https://doi.org/10.3390/molecules25071521