Ulinastatin attenuates lipopolysaccharide‑induced cardiac dysfunction by inhibiting inflammation and regulating autophagy

Abstract

Ulinastatin exerts protective effects against lipopolysaccharide (LPS)-induced cardiac dysfunction. Autophagy has been demonstrated to serve an important role in sepsis-induced cardiomyopathy; however, whether ulinastatin has an anti-autophagic effect in sepsis requires further investigation. The present study aimed to determine the protective effects of ulinastatin on cardiac dysfunction and its role in autophagy during sepsis. C57BL/6J mice were randomly divided into a control, LPS and LPS + ulinastatin group, the survival status of the mice was observed every 6 h and the survival rate at each time point was calculated for 7 days. Furthermore, JC-1 dye and ELISAs were used to analyze the mitochondrial membrane potential (MMP) and serum cardiac troponin I (cTnI) levels, respectively. Western blotting and ELISAs were used to measure the levels of tumor necrosis factor (TNF)-α and interleukin (IL)-6. In addition, the cardiac ultrastructure and the number of autophagosomes formed were visualized using transmission electron microscopy, and the pathological changes in the myocardial tissues were analyzed using hematoxylin & eosin staining. Finally, the expression levels of autophagy-related proteins were analyzed using western blotting and immunofluorescence staining. The current study indicated that ulinastatin significantly improved the survival rate of septic mice. It was suggested that ulinastatin may protect against LPS-induced myocardium injury through its anti-inflammatory activity, as decreased cTnI levels, increased MMP and decreased expression levels of TNF-α and IL-6 were all observed following ulinastatin treatment. Furthermore, the number of autophagosomes formed, and the expression levels of microtubule-associated protein light chain 3 and Beclin 1 were significantly decreased following ulinastatin treatment. It was further observed that ulinastatin suppressed LPS-induced autophagosome formation, as indicated by the accumulation of sequestosome 1/p62, and the elimination of lysosome-associated membrane glycoprotein 1. In conclusion, the results of the present study suggested that ulinastatin treatment may improve survival and exert a protective effect over LPS-induced cardiac dysfunction. Furthermore, this protective effect may be associated with its anti-inflammatory and anti-autophagic activity.

Interdependence of Anti-Inflammatory and Antioxidant Properties of Squalene–Implication for Cardiovascular Health

“…Due to these modulations, the LPS-induced model is excellent for the screening and subsequent evaluation of potential drugs or natural products on the inflammatory pathway [ 79 ]. LPS induction causes endotoxemia, which is related to a significant increase in cardiac dysfunction [ 80 ], triggered via toll-like receptor 4 (TLR-4)-mediated inflammatory responses. The trigger leads to a chronic low-grade pro-inflammatory condition, namely, metabolic endotoxemia (ME), which is usually high in CVD patients [ 81 ] Following administration of SQ at 25 and 50 µM for 18 h, the in vitro study conducted by Cardeno et al (2015), demonstrated attenuation in the inflammatory events caused by the LPS induction ( Table 2 ) [ 57 ].…”

Ulinastatin improves renal microcirculation by protecting expression of VE-cadherin and inhibiting autophagy in a septic rat model

“…Previous studies have shown that ulinastatin inhibits autophagy, and in myocardial IR injury, ulinastatin exhibits a myocardial protective effect against IR injury, but ulinastatin was found to downregulate the LC3-II protein expression [38]. Ulinastatin exerts protective effects against lipopolysaccharide-induced cardiac dysfunction, and may be associated with its anti-in ammatory and anti-autophagic activity [39].…”

Jujuboside A Attenuates Sepsis-Induced Cardiomyopathy By Inhibiting Inflammation and Regulating Autophagy

“…Recent investigations suggest that appropriate autophagy modulation has a potential role to improve cardiac function by regulating mitochondria and attenuating in ammation in SIC; moreover, the role of autophagy during the pathogenesis of sepsis has been under intensive exploration in recent years [62,65,66]. Previous studies have shown that multiple medicine and bioactive molecules exert cardioprotective effects by regulating autophagy in sepsis [70][71][72][73][74][75]. In this study, we explored the potential role of JuA in SIC.…”