title: New K-Oximes (K-27 and K-48) in Comparison with Obidoxime (LuH-6), HI-6, Trimedoxime (TMB-4), and Pralidoxime (2-PAM): Survival in Rats Exposed IP to the Organophosphate Paraoxon.
abstract: ABSTRACT Oximes are cholinesterase reactivators used in organophosphorus compound poisoning. The purpose of the study was to compare the protective effect of the K-oximes (K-27 and K-48) in male rats with that of obidoxime (LuH-6), trimedoxime (TMB-4), and HI-6, using paraoxon (POX) as a cholinesterase inhibitor. Pralidoxime (2-PAM) was also retested. Seven groups of six rats each were used. Group 1 (G(1)) received 1 mumol/rat POX ( approximately LD(75)), the other groups (G(2-7)) received 1 mumol/rat POX + one of the six reactivators. The animals were monitored for 48 h and time of mortality was recorded. The procedure was repeated seven times. Subsequently, experiments as described were repeated using 10 and 15 mumol/rat POX. Mortality data were compared and hazards ratios (relative risks) ranked with the Cox proportional hazards model using the POX dose and group (reactivator) as time-independent covariables. K-27 followed by K-48 were the most potent reactivators. K-27 was statistically significantly superior to all other reactivators except K-48. The relative risk of death estimated by Cox analysis in K-27- and K-48-treated animals when compared with untreated animals, adjusted for the POX dose, was 0.22 (95% confidence interval [CI], 0.15 to 0.31) and 0.26 (95% CI, 0.18 to 0.37), respectively. We concluded that in the animal model used K-27 and K-48 are superior to older oximes in their ability to protect from paraoxon effects. They should be tested further using methyl- and propyl-organophosphates as toxic agents.
authors.affiliation: United Arab Emirates University, Al Ain-United Arab Emirates.
authors.forename: G A
authors.initials: GA
authors.lastname: Petroianu
authors.forename: M Y
authors.initials: MY
authors.lastname: Hasan
authors.forename: S M
authors.initials: SM
authors.lastname: Nurulain
authors.forename: N
authors.initials: N
authors.lastname: Nagelkerke
authors.forename: J
authors.initials: J
authors.lastname: Kassa
authors.forename: K
authors.initials: K
authors.lastname: Kuca