Possible antidotes in severe intoxication with fenitrothion in rats

Area of Science:

• Toxicology
• Pharmacology

Background:

• Fenitrothion is an organophosphate insecticide posing acute poisoning risks.
• Effective antidotal therapies are crucial for managing fenitrothion toxicity.

Purpose of the Study:

• To investigate the efficacy of nine different drugs as antidotes against acute fenitrothion poisoning in a rat model.
• To evaluate the impact of these drugs on survival ratio, survival time, and toxic signs.

Main Methods:

• Acute fenitrothion poisoning was induced in rats at approximate LD50 (500 mg/kg) and 100% lethal dose (800 mg/kg) levels.
• The effects of nine drugs, including oximes (2-PAM, TPMM), diphenhydramine, parasympatholytics (atropine, scopolamine, biperiden), reduced glutathione, and central depressants (diazepam, phenobarbital), were assessed.
• Antidotal effects were measured by relief from toxic signs, increased survival ratio, and prolonged survival time.

Main Results:

• Oximes (2-PAM, TPMM), diphenhydramine, and parasympatholytics significantly improved survival in rats poisoned with approximate LD50 fenitrothion.
• Parasympatholytics effectively reduced signs like salivation, miosis, and motor ataxia.
• Reduced glutathione and central depressants exacerbated poisoning.
• In severe poisoning (800 mg/kg), parasympatholytics increased survival to 20-40%.
• Combined and repeated administration of atropine and 2-PAM achieved a 90% survival rate and alleviated toxic signs.

Conclusions:

• Certain drugs, particularly parasympatholytics and oximes, demonstrate significant antidotal effects against fenitrothion poisoning.
• Combined therapy with atropine and 2-PAM is the most effective treatment for severe fenitrothion poisoning in rats.
• Further research into optimal antidotal strategies for organophosphate poisoning is warranted.