Experimental and Established Oximes as Pretreatment before Acute Exposure to Azinphos-Methyl
Abstract
:1. Introduction
2. Results
2.1. Mortality Rates
2.2. Cox Survival Analysis
3. Discussion
4. Materials and Methods
4.1. Chemicals
4.2. Experimental Animals
4.2.1. Choice of Dosage for Pretreatment
- Reference group: only azinphos-methyl exposure.
- Pyridostigmine: 1 µmol/rat = 0.26 mg/rat (= 1.0 mg/kg average body weight).
- Pralidoxime: 30 µmol/rat = 5.2 mg/rat (= 20 mg/kg average body weight).
- Obidoxime: 25 µmol/rat = 9.0 mg/rat (=35 mg/kg average body weight).
- K-27: 60 µmol/rat = 26.8 mg/rat (=103 mg/kg average body weight).
- K-48: 25 µmol/rat = 11.5 mg/rat (=44 mg/kg average body weight).
- K-53: 3 µmol/rat = 1.37 mg/rat (=5.3 mg/kg average body weight).
- K-74: 3 µmol/rat = 1.38 mg/rat (=5.3 mg/kg average body weight).
- K-75: 3 µmol/rat = 1.37 mg/rat (=5.3 mg/kg average body weight).
4.2.2. Pretreatment and Azinphos-Methyl Exposure
Molecular Weight | Injected Dose (µmol/rat) | Injected Dose (mg/rat) | Injected Dose (mg/kg Average Body Weight) | IC50 Human (µM] | IC50 Rat (µM) | LD50/LD01 (µmol/rat) | |
---|---|---|---|---|---|---|---|
Azinphos-methyl | 317.3 | 5, 10, 15 | 1.59, 3.18, 4.77 | 6.14, 12.28, 18.42 | 189 * | NA | 3.2/0.4 * |
Pyridostigmine | 172.60 | 30 | 0.26 | 1.0 | 0.33 | NA | 7.2/3.7 |
Pralidoxime | 172.60 | 30 | 5.2 | 20 | 592 | 412 | 180/117 |
Obidoxime | 359.21 | 25 | 9.0 | 35 | 702 | 193 | 132/107 |
K-27 | 446.16 | 60 | 26.8 | 103 | 414 | 1054 | 350/250 |
K-45 | 460.16 | 25 | 11.5 | 44 | 461 | 643 | 140/110 |
K-53 | 458.15 | 3 | 1.37 | 5.3 | 115 | 83 | 21/13 |
K-74 | 460.16 | 3 | 1.38 | 5.3 | 103 | 66 | 28/13 |
K-75 | 458.15 | 3 | 1.37 | 5.3 | 63 | 101 | 51/13 |
4.3. Statistical Analysis
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Acknowledgments
Conflicts of Interest
References
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Substance | Structure |
---|---|
Azinphos-methyl | |
Pyridostigmine | |
Pralidoxime | |
Obidoxime | |
K-27 | |
K-48 | |
K-53 | |
K-74 | |
K-75 |
Groups (G) | 10 min | 30 min | 1 h | 2 h | 3 h | 4 h | 24 h | 48 h |
---|---|---|---|---|---|---|---|---|
G1: Azinphos-methyl only | 71/92/92 | 71/92/96 | 71/92/100 | 71/92/100 | 71/92/100 | 71/92/100 | 75/92/100 | 75/92/100 |
G2: Pyridostigmine pretreatment | 29/50/71 | 42/54/75 | 42/54/79 | 42/58/83 | 42/58/88 | 42/58/88 | 46/58/88 | 46/58/88 |
G3: Pralidoxime pretreatment | 21/33/54 | 21/50/58 | 21/50/67 | 25/50/71 | 25/63/71 | 25/63/71 | 25/63/71 | 25/63/71 |
G4: Obidoxime pretreatment | 4/8/21 | 4/8/21 | 4/8/42 | 4/29/42 | 4/29/54 | 4/29/54 | 17/46/63 | 17/46/67 |
G5: K-27 pretreatment | 21/0/4 | 21/4/13 | 21/4/13 | 21/4/25 | 29/4/29 | 29/42/29 | 50/46/46 | 50/50/46 |
G6: K-48 pretreatment | 0/8/8 | 8/13/13 | 8/13/21 | 8/13/21 | 8/13/38 | 8/13/38 | 25/50/58 | 25/54/58 |
G7: K-53 pretreatment | 13/33/29 | 29/33/42 | 29/33/50 | 29/46/63 | 29/50/63 | 29/50/63 | 38/54/71 | 38/54/71 |
G8: K-74 pretreatment | 0/8/17 | 17/8/25 | 17/8/38 | 17/13/46 | 17/33/50 | 17/50/50 | 33/58/54 | 33/58/54 |
G9: K-75 pretreatment | 4/17/33 | 33/21/50 | 38/21/58 | 38/25/58 | 38/38/58 | 42/42/58 | 50/50/63 | 50/58/67 |
Groups | Relative Risk (RR) | 95% CI | p-Value |
---|---|---|---|
Azinphos-methyl only | 1 | reference | reference |
Pyridostigmine + azinphos | 0.52 ± 0.10 | 0.36–0.68 | ≤0. 01 |
Pralidoxime + azinphos | 0.37 ± 0.03 | 0.33–0.41 | ≤0. 01 a |
Obidoxime+ azinphos | 0.21 ± 0.09 | 0.06–0.36 | ≤0. 01 a, b |
K-27 + azinphos | 0.23 ± 0.02 | 0.20–0.25 | ≤0.01 a, b, c |
K-48 + azinphos | 0.20 ± 0.03 | 15–0.24 | ≤0.01 a, b, c |
K-53 + azinphos | 0.37 ± 0.14 | 0.14–0.59 | ≤0.01 |
K-74 + azinphos | 0.26 ± 0.10 | 0.09–0.42 | ≤0.01 a |
K-75 + azinphos | 0.35 ± 0.03 | 0.30–0.39 | ≤0.01 a |
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Lorke, D.E.; Nurulain, S.M.; Hasan, M.Y.; Kuča, K.; Petroianu, G.A. Experimental and Established Oximes as Pretreatment before Acute Exposure to Azinphos-Methyl. Int. J. Mol. Sci. 2021, 22, 3072. https://doi.org/10.3390/ijms22063072
Lorke DE, Nurulain SM, Hasan MY, Kuča K, Petroianu GA. Experimental and Established Oximes as Pretreatment before Acute Exposure to Azinphos-Methyl. International Journal of Molecular Sciences. 2021; 22(6):3072. https://doi.org/10.3390/ijms22063072
Chicago/Turabian StyleLorke, Dietrich E., Syed M. Nurulain, Mohamed Y. Hasan, Kamil Kuča, and Georg A. Petroianu. 2021. "Experimental and Established Oximes as Pretreatment before Acute Exposure to Azinphos-Methyl" International Journal of Molecular Sciences 22, no. 6: 3072. https://doi.org/10.3390/ijms22063072