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Oral treatment of organophosphate poisoning in mice
Bradford J Bowls1, Jack M Freeman, James A Luna
1Department of Emergency Medicine, Brody Medical School at East Carolina University, Greenville, NC 27858, USA.
Objective:
Organophosphates are used as pesticides, herbicides, and chemical warfare agents. Treatment of organophosphate poisoning is with intravenous atropine and pralidoxime in addition to supportive care. This study determined the efficacy of oral agents in preventing death from organophosphate poisoning.
Methods:
The organophosphate paraoxon (8 mg/kg) was used in a murine model with lethality at four and 24 hours as an end point. For oral treatment, 15 male Balbc mice were given either atropine sulfate (4 mg/kg), or a combination of atropine sulfate (4 mg/kg) with pralidoxime (100 mg/kg), by oral gavage. A control group of 22 mice received water by oral gavage. Chi-square analysis was used to compare results in the different groups.
Results:
Of the control group, six of 22 survived to four hours after paraoxon exposure. Of the exposed animals treated with oral atropine, eight of 15 survived to four hours. Of the exposed animals treated with a combination of atropine and pralidoxime, 13 of 15 survived to four hours. All animals surviving to four hours survived to 24 hours. The increased survival of animals in the atropine group relative to the control group was not significant (p = 0.09). Survival was significant in the group treated with atropine and pralidoxime relative to atropine alone (p = 0.02) and to the control group (p = 0.0002). All treated mice surviving at four hours were alive at 24 hours.
Conclusions:
Both oral atropine and a combination of oral atropine and pralidoxime improved survival, and combination therapy achieved statistical significance. Generalization of this result to other organophosphate pesticides, other doses of paraoxon, and other species cannot be made without further investigations.
Insights
Oral atropine and pralidoxime combination therapy significantly improved survival in a murine model of organophosphate poisoning. This study explored oral agents for preventing death from organophosphate exposure.
Area of Science:
- Toxicology
- Pharmacology
Background:
- Organophosphates are widely used as pesticides and herbicides.
- Organophosphate poisoning requires prompt treatment with intravenous atropine and pralidoxime.
- Efficacy of oral administration of these agents remains to be fully elucidated.
Purpose of the Study:
- To determine the efficacy of oral atropine and pralidoxime in preventing mortality from organophosphate poisoning in a murine model.
Main Methods:
- A murine model was exposed to paraoxon (8 mg/kg).
- Mice received oral atropine sulfate (4 mg/kg) or a combination of atropine (4 mg/kg) and pralidoxime (100 mg/kg) via oral gavage.
- A control group received water; survival at 4 and 24 hours was assessed using chi-square analysis.
Main Results:
- Survival rates at 4 hours were 36% (control), 53% (atropine alone), and 87% (atropine + pralidoxime).
- Combination therapy showed statistically significant improvement in survival compared to atropine alone (p=0.02) and the control group (p=0.0002).
- All mice surviving 4 hours also survived to 24 hours.
Conclusions:
- Oral atropine and combination therapy with oral atropine and pralidoxime enhanced survival in organophosphate-poisoned mice.
- Combination therapy demonstrated statistically significant efficacy.
- Further research is needed to generalize findings to other organophosphates, doses, and species.
