Sulfur dioxide attenuates sepsis-induced cardiac dysfunction via inhibition of NLRP3 inflammasome activation in rats.

OBJECTIVE

Sulfur dioxide (SO) plays an important role in maintaining homeostasis of cardiovascular system. This study was aimed to investigate cardioprotective effects of SO on in the rat and the underlying mechanism.

METHODS AND RESULTS

Sepsis model induced by cecal ligation and puncture (CLP) in rats were used. SO donor (NaHSO/NaSO, 1:3 M/M) was administered intraperitoneally at a dose of 85 mg/kg. Primary neonatal rat cardiac ventricular myocytes (NRCMs) were stimulated with LPS (1 mg/mL) in presence or absence of different concentrations of SO (10, 50 and 100 μmol/L). SO donor could restore the decreased levels of SO in plasma and heart of septic rats. SO exhibited dramatic improvement in cardiac functions. At 24 h after CLP, SO treatments decreased the number of TUNEL-positive cells, Bax/Bcl-2 ratio and activity of caspase-3. Moreover CLP-induced inflammatory response was also relieved by SO. In NRCMs, SO could suppress the LPS-induced myocardial injury, leading to an increase in cell viability, a decrease in LDH and apoptotic rate. Western blot showed that the expression of TLR4, NLRP3, and Caspase-1 were obviously increased in myocardial tissue of CLP group or in NRCMs of LPS group, while SO significantly inhibited the CLP-induced or LPS-induced TLR4, NLRP3, and Caspase-1 expression.

CONCLUSION

SO attenuated sepsis-induced cardiac dysfunction likely in association with the inhibiting inflammation via TLR4/NLRP3 signaling pathway.