The effects of lazaroid U-74389G in a rat sepsis model

Abstract

Lazaroid treatment of E. coli-inoculated septic animals lessens the hemodynamic deterioration seen in sepsis.

Effects of epinephrine on heart rate variability and cytokines in a rat sepsis model

“…Moreover, short term pre-exposure of healthy subjects to EPI before injection of low-dose endotoxin decreased the secretion of the pro-inflammatory cytokine TNF-α and stimulated the production of the anti-inflammatory IL-10 [31]. In our previous study [2], the concentrations of IL-6 and TNF-α were the highest 2 hours after E. coli inoculation in immunocompromised rats and then subsequently www.bjbms.org decreased at 6 hours, while IL-1β levels stayed approximately the same. In the current study, the concentrations of TNF-α, IL-1β, and IL-6 were all higher after LPS intravenous infusion in rats, peaking at 2 hours.…”

“…In our previous study [2], we demonstrated that the concentrations of the inflammatory mediators IL-6 and TNF-α were the highest 2 hours after Escherichia coli (E. coli) inoculation in irradiated immunocompromised rats and subsequently were decreased at 6 hours; on the contrary, IL-1β levels stayed approximately the same at all time points examined. Both major HRV components, LF and HF, were decreased during the early hyperdynamic phase after bacteria inoculation.…”

“…Both major HRV components, LF and HF, were decreased during the early hyperdynamic phase after bacteria inoculation. Similarly, HR parameters decreased two hours after E. coli inoculation, indicating that impaired autonomic nervous control of the cardiovascular system is due to sepsis [2].…”

“…Despite advances in the treatment of sepsis, including its most severe form septic shock, the mortality rate ranges from 30% to as high as 76% [1,2]. In critical care patients, sepsis syndrome and multiple organ dysfunction syndrome (MODS) are the leading cause of death [3].…”

Lazaroid U-74389G inhibits the osteoblastic differentiation of IL-1β-indcued aortic valve interstitial cells through glucocorticoid receptor and inhibition of NF-κB pathway

“…U-74389G has been clinically developed as a potential drug to protect against ischemia/ reperfusion injury of the central nervous and liver, but did not achieve regulatory approval [11,12]. The use of antioxidants in inflammatory diseases has been widely advocated and studies suggested that U-74389G and other 21-aminosteroids are potent inhibitors of the synthesis of several pro-inflammatory cytokines, such as IL-6, IL-8, interferon-g (IFN-g) and tumor necrosis factor-a (TNF-a) [13,14].…”