Pharmacologic studies on ET-26 hydrochloride in a rat model of lipopolysaccharide-induced sepsis.

Abstract

BACKGROUND:

ET-26 hydrochloride (ET-26 HCl) is a promising sedation-hypnotic compound with stable hemodynamic features that elicits virtually no adrenocortical suppression. However, whether it preserves better pharmacologic characteristics in a rat model of sepsis is not known. This study compared the survival rate, levels of corticosterone and pro-inflammatory cytokines, and histologic injury in the lungs and kidneys of rats suffering from sepsis treated with ET-26 HCl, etomidate, or normal saline (NS).

METHODS:

Rats were given lipopolysaccharide (1mg/kg body weight, i.v.) to establish a sepsis model. Thirty minutes after lipopolysaccharide administration, ET-26 HCl, etomidate or NS were given as a bolus injection at equivalent doses. Plasma levels of corticosterone, interleukin-1β, interleukin-6, interleukin-10, and tumor necrosis factor-α were measured 1, 2, 4, 6 and 24h after administration. Histologic injury was observed at the time of death or 24h after drug administration.

RESULTS:

The survival rate for rats in the etomidate, ET-26 HCl and NS groups was 40%, 90% and 90%, respectively. Corticosterone concentrations in the etomidate group were lower than those in the other groups 1h after administration of hypnotic compounds. Concentrations of pro-inflammatory cytokines in the ET-26 HCl group and NS group were not significantly different, but were significantly lower than those in the etomidate group. The injury scores of kidneys and lungs in the etomidate group were higher than those in ET-26 HCl and NS groups.

CONCLUSIONS:

ET-26 HCl showed virtually no suppression of corticosterone synthesis, lower concentrations of pro-inflammatory cytokines, higher survival rate, and less organ injury in rats suffering from sepsis compared with the etomidate group. It may be safer to induce anesthesia using ET-26 HCl, rather than etomidate, in patients suffering from sepsis.

• Authors: Bin Wang, Junli Jiang, Jun Yang, Jun Chen, Zhaoqiong Zhu, Jin Liu, Wensheng Zhang
• Journal: European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences (Eur J Pharm Sci) Vol. 109 Pg. 441-445 (Nov 15 2017) ISSN: 1879-0720 [Electronic] Netherlands
• PMID: 28882766 (Publication Type: Journal Article)
• Copyright: Copyright © 2017 Elsevier B.V. All rights reserved.

Chemical References

• Cytokines
• ET-26 compound
• Hypnotics and Sedatives
• Lipopolysaccharides
• Corticosterone
• Etomidate

Topics

• Animals
• Corticosterone (blood)
• Cytokines (blood)
• Etomidate (analogs & derivatives, pharmacology)
• Female
• Hypnotics and Sedatives (pharmacology)
• Kidney (drug effects, pathology)
• Lipopolysaccharides
• Lung (drug effects, pathology)
• Male
• Rats
• Rats, Sprague-Dawley
• Sepsis (blood, pathology)