Hydrogen-Rich Saline Inhibits NLRP3 Inflammasome Activation and Attenuates Experimental Acute Pancreatitis in Mice

Abstract

Increasing evidence has demonstrated that reactive oxygen species (ROS) induces oxidative stress and plays a crucial role in the pathogenesis of acute pancreatitis (AP). Hydrogen-rich saline (HRS), a well-known ROS scavenger, has been shown to possess therapeutic benefit on AP in many animal experiments. Recent findings have indicated that the NOD-like receptor family, pyrin domain-containing 3 (NLRP3) inflammasome, an intracellular multiprotein complex required for the maturation of interleukin- (IL-) 1β, may probably be a potential target of HRS in the treatment of AP. Therefore, in this study, we evaluated the activation of NLRP3 inflammasome and meanwhile assessed the degree of oxidative stress and inflammatory cascades, as well as the histological alterations in mice suffering from cerulein-induced AP after the treatment of HRS. The results showed that the activation of NLRP3 inflammasome in AP mice was substantially inhibited following the administration of HRS, which was paralleled with the decreased NF-κB activity and cytokines production, attenuated oxidative stress and the amelioration of pancreatic tissue damage. In conclusion, our study has, for the first time, revealed that inhibition of the activation of NLRP3 inflammasome probably contributed to the therapeutic potential of HRS in AP.

Intravenous hMSCs Ameliorate Acute Pancreatitis in Mice via Secretion of Tumor Necrosis Factor-α Stimulated Gene/Protein 6

“…As an important component of the innate immune system, the NLRP3 inflammasome could be activated by endogenous molecules known as damage-associated molecular patterns (DAMPs), such as DNA, adenosine triphosphate (ATP), high mobility group box 1 (HMGB1), and nucleotide binding oligomerization domain 2 (NOD2) which are all associated with inflammation during the development of pancreatitis. Furthermore, components of the inflammasome, specifically ASC, caspase-1, and NLRP3, are required for the development of inflammation in acute pancreatitis85758. Taken together with our results, these findings suggest that TSG-6 can act as an antagonist of the NLRP3 inflammasome, resulting in attenuation of cellular inflammatory processes and consequent relief of pancreatic injury during SAP.…”

Sulforaphane Protects Pancreatic Acinar Cell Injury by Modulating Nrf2‐Mediated Oxidative Stress and NLRP3 Inflammatory Pathway

“…Reduction of oxidative stress by the antioxidant hydrogen suppressed activation of NLRP3 inflammasome and maturation of IL-1 β that have deepened current understanding of antioxidants in managing AP [12]. Our data revealed that NLRP3 inflammasome activation is associated with cerulein-induced inflammation in acini and suppressed by SFN.…”

“…Also, oxidative stress contributes to not only the amplification of pancreatic damage but also the progression of local inflammation to systemic inflammatory responses [6]. Therefore, supplementation with exogenous antioxidants represents a beneficial therapeutic strategy or a useful adjunctive option in the treatment of AP [11, 12]. …”

“…In addition, SFN has been reported to inhibit multiple inflammasomes in immune cells [18]. Recent findings indicate that the nucleotide-binding domain leucine-rich repeat containing family, pyrin domain-containing 3 (NLRP3) inflammasome, provides the link between acinar cell death and inflammation during the development of AP; and activation of NLRP3 inflammasome is involved in the development of AP [19], which is inhibited by antioxidants like hydrogen-rich saline [12]. …”

Hydrogen-Rich Saline Attenuated Subarachnoid Hemorrhage-Induced Early Brain Injury in Rats by Suppressing Inflammatory Response: Possible Involvement of NF-κB Pathway and NLRP3 Inflammasome

“…There have been several studies focusing on the neuroprotective effects of HS in other nerve injury models, such as focal ischemia and reperfusion [53], Parkinson's disease [54], brain &p<0.05 vs. SAH group; &&p<0.01 vs. SAH group; @ p<0.05 vs. SAH+vehicle group; @@ p<0.01 vs. SAH+vehicle group stem infarct [55], intracerebral hemorrhage [56], neonatal hypoxia-ischemia [57], traumatic brain injury [58], spinal cord injury [59], et al, and numerous articles demonstrated that HSinduced beneficial effect is partially involved of NF-κB pathway [60][61][62]53]. As a well-established representative of inflammation, NF-κB has been reported to be activated after SAH [63][64][65].…”