Silibinin protects against sepsis and septic myocardial injury in an NR1H3-dependent pathway

This study, for the first time, examined the effects and mechanisms of SIL pretreatment, posttreatment and in combination with classical antibiotics in septic myocardial injury. The survival rate, sepsis score, anal temperature, routine blood parameters, blood biochemical parameters, cardiac function indicators, pathological indicators of myocardial tissue injury, NR1H3 signaling pathway, and several sepsis-related signaling pathways were detected 8 h after cecal ligation and puncture (CLP). Our results showed that SIL pretreatment showed a significant protective effect on sepsis and septic myocardial injury, which was explained by the attenuation of inflammation, inhibition of oxidative stress, improvement of mitochondrial function, regulation of endoplasmic reticulum stress (ERS), and activation of the NR1H3 pathway. SIL posttreatment and the combination of SIL and azithromycin (AZI) showed a certain therapeutic effect. RNA-seq detection further clarified the myocardial protective mechanisms of SIL. This study provides a theoretical basis for the application strategy and combination of SIL in septic myocardial injury.PMID:35640818 | DOI:10.1016/j.freeradbiomed.2022.05.018
Source: Free Radical Biology and Medicine - Category: Biology Authors: Source Type: research