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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
pharmacology, toxicology and pharmaceutics
Five oximes (K-27, K-48, obidoxime, HI-6 and trimedoxime) in comparison with pralidoxime: Survival in rats exposed to methyl-paraoxon
Journal of Applied Toxicology, Volume 27, No. 5, Year 2007
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Description
There is a clear need for broad-spectrum cholinesterase reactivators (active against a multitude of organophosphorus ester enzyme inhibitors) with a higher efficacy than pralidoxime. The purpose of the study was to quantify in vivo the extent of oxime-conferred protection, using methyl-paraoxon [dimethyl p-nitrophenyl phosphate; (methyl-POX)] as a cholinesterase inhibitor. There were seven groups of six rats in each cycle of the experiment. Group 1 (G1) received 2 μmol methyl-POX (≈ LD50), the other groups (G2-7) received 2 μmol methyl-POX + one of the six reactivators. The animals were monitored for 48 h and the time of mortality was recorded. The procedure was repeated six times. All substances were applied i.p. The experiments were repeated using 3 and 5 μmol methyl-POX. Mortality data were compared and hazards ratios (relative risks) ranked using the Cox proportional hazards model with methyl-POX dose and group (reactivator) as time-independent covariables. The relative risk of death estimated by Cox analysis (95% CI) in oxime-treated animals when compared with untreated animals, adjusted for methyl-POX dose (high/low) was K-27, 0.58 (0.42-0.80); K-48, 0.60 (0.43-0.83); trimedoxime, 0.76 (0.55-1.04); pralidoxime, 0.88 (0.65-1.20); obidoxime, 0.93 (0.68-1.26); HI-6, 0.96 (0.71-1.31). Only K-27 and K-48 provided statistically significant protection in rats exposed to methyl-POX. Despite the lower inhibitory potency (higher IC50) of methyl-POX compared with POX (ratio 4:1), the ability of oxime reactivators to protect from methyl-POX induced mortality was reduced compared with protection from POX (ethyl-analog). Copyright © 2007 John Wiley & Sons, Ltd.
Authors & Co-Authors
Petroianu, Georg
United Arab Emirates, Al Ain
United Arab Emirates University
Nurulain, Syed Muhammad
United Arab Emirates, Al Ain
United Arab Emirates University
Nagelkerke, Nico J.D.
United Arab Emirates, Al Ain
United Arab Emirates University
Shafiullah, Mohamed M.
United Arab Emirates, Al Ain
United Arab Emirates University
Kassa, J.
Czech Republic, Brno
Univerzita Obrany V Brne
Kuca, Kamil
Czech Republic, Brno
Univerzita Obrany V Brne
Statistics
Citations: 50
Authors: 6
Affiliations: 2
Identifiers
Doi:
10.1002/jat.1224
ISSN:
0260437X
e-ISSN:
10991263
Study Approach
Quantitative