Protection against fatal endotoxin shock in mice by antihistamines

Area of Science:

• Pharmacology
• Toxicology
• Immunology

Background:

• Previous studies suggest antihistamines can protect against endotoxin shock.
• The efficacy of this treatment requires further validation through animal experimentation.

Purpose of the Study:

• To evaluate the protective effects of diphenhydramine and hydroxyzine against gram-negative endotoxin shock in a mouse model.
• To determine the optimal timing for hydroxyzine administration to maximize protection.

Main Methods:

• Determined the lethal dose 80 (LD80) of endotoxin in mice (36 mg/kg).
• Administered varying doses of diphenhydramine or hydroxyzine HCI one hour before LD80 endotoxin.
• Assessed survival rates and toxic effects of the antihistamines.
• Investigated the impact of hydroxyzine administration timing (from 6 hours prior to 3 hours after endotoxin).

Main Results:

• High doses (40-50 mg/kg) of both drugs were fatal, causing convulsions.
• Doses below 1 mg/kg showed no protective effect.
• Doses of 2.5 and 5 mg/kg provided some protection.
• 5 mg/kg diphenhydramine pretreatment resulted in 60% survival.
• 1 hour prior pretreatment with hydroxyzine yielded 90-100% survival.
• Simultaneous administration of hydroxyzine with endotoxin resulted in 100% survival.
• Delayed administration (1 and 3 hours post-endotoxin) showed reduced survival rates (70% and 40%, respectively).

Conclusions:

• Diphenhydramine and hydroxyzine demonstrate protective potential against endotoxin shock in mice.
• Hydroxyzine is most effective when administered concurrently with endotoxin.
• Timing of administration is critical for the therapeutic efficacy of hydroxyzine in endotoxin shock.