Effects of propofol and etomidate pretreatment on glucocorticoid receptor expression following induction of sepsis in rats

Abstract

ABSTRACT. The aim of this study was to determine the effect of etomidate and propofol pretreatment on the expression of glucocorticoid receptor and the prognosis of sepsis. The sepsis rat was used as a model. During glucocorticoid treatment, etomidate and propofol were applied alone or together at different time points. Survival curves, glucocorticoid receptor expression in the rat adrenal cortex, and inflammation levels were determined. The outcome of sepsis in rats was evaluated based on the combined utilization of propofol and etomidate. The results indicated that the combined utilization of propofol and etomidate pretreatment could significantly improve the effects of glucocorticoids on rat sepsis. Etomidate was shown to enhance the expression of the glucocorticoid receptor, while propofol was shown to inhibit the inflammatory response. Etomidate was best used immediately after modeling, whereas propofol was most suitable for use during the peak inflammatory reaction. These results demonstrated that anesthetics had 4741 Propofol and etomidate effects on GR in rats with sepsis ©FUNPEC-RP www.funpecrp.com.br Genetics and Molecular Research 14 (2): 4740-4748 (2015) the ability to enhance the effect of glucocorticoids in the treatment of sepsis. Etomidate was indicated for use in the early stage of inflammation to enhance expression of the glucocorticoid receptor, while propofol application was indicated at the peak of the inflammatory reaction owing to its strong anti-inflammation effect.

The effects of etomidate on expression of high mobility group box 1 via the nuclear factor kappa B pathway in rat model of sepsis

“…However, studies assessing the effects of etomidate on the expression and release of HMGB1 related to pro-inflammatory cytokines and NF-ĸB pathways under septic conditions are limited in number. The results of this study are similar to those of previous studies that suggest protective effects of etomidate on inflammation [ 32 , 33 ]. Because increased HMGB1 concentration correlates with organ injury and poor prognosis in sepsis [ 6 , 24 ], HMGB1 could be a potential target for sepsis treatment [ 3 , 5 ].…”

“…Therefore, in vitro or in vivo studies using animals have been performed to reveal the effects of etomidate on inflammation or mortality [ 15 , 31 ]. The anti-inflammatory effects of etomidate have been suggested in several previous studies [ 15 , 31 , 32 ], but in vivo studies using CLP-induced septic rats have offered inconsistent results regarding mortality [ 31 , 33 , 34 ]. Zhang et al reported that etomidate inhibited the serum mRNA expression of TNF-α and IL-6 and NF-ĸB activation, but the mortality of etomidate-treated septic rats was increased due to lymphocyte apoptosis rather than adrenal suppression [ 31 , 34 ].…”

“…Zhang et al reported that etomidate inhibited the serum mRNA expression of TNF-α and IL-6 and NF-ĸB activation, but the mortality of etomidate-treated septic rats was increased due to lymphocyte apoptosis rather than adrenal suppression [ 31 , 34 ]. However, Wang et al reported that etomidate treatment resulted in better survival rates by decreasing IL-1 and TNF-α levels and enhancing glucocorticoid receptor expression in septic rats [ 33 ]. An in vitro study supports the results of Wang et al, suggesting that etomidate treatment attenuates TNF-α, IL-6, and cluster of differentiation 14 levels; triggers receptors expressed on myeloid cells-1; and inhibits NF-κB activation in LPS-stimulated macrophages [ 15 ].…”

“…Second, we did not investigate the degree of adrenal insufficiency. Previous studies have suggested that the mortality rate and degree of adrenal injury do not positively correlate in septic rats with etomidate treatment [ 33 , 34 ], and the inhibitory effects of etomidate on steroidogenesis have been revealed in human studies [ 9 ]. Third, we assessed the effects of a single fixed dose of etomidate in sepsis.…”

“…In previous studies, etomidate was administered to mice at doses ranging from 0.3 to 30 mg/kg [ 14 , 37 ]. We chose to administer a dose of 4 mg/kg for etomidate immediately after surgery in this study because a previous study demonstrated that this dose of etomidate results in better survival than lower (0.6 mg/kg) or higher (10 mg/kg) doses of etomidate in septic rats, and etomidate is most effective when used immediately after modeling [ 31 , 33 ]. Finally, we evaluated septic rats over a relatively short period of 24 h. A prospective, noninterventional study of patients with sepsis found that HMGB1 levels gradually, though not statistically significant, decreased in survivors, whereas they increased between days 1 and 3 in nonsurvivors [ 6 ].…”