Aspartae a Novel Treatment for Acute Pancreatitis

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Introduction: There is growing evidence that metabolic intermediates and products can modulate inflammatory responses. Acute pancreatitis (AP) affects more than 200,000 people each year in the United States. A hallmark of AP is the frequent rapid progression into a severe inflammatory response which is associated with pancreatic necrosis and multi-organ failure. The ability of non-infectious insults to initiate severe inflammation is a poorly understood feature of AP, and clinical management is currently limited to supportive care Aims: To Test if aspartate has a role in the treatment of acute pancreatitis in wild type mice via modulation of TLR4 pathway and NLRP3 Inflammasome which are the key players of sterile inflammation. Methods: C56BL/6N young adult male mice were administered caerulein sulfate at 100 pg per g body weight in sterile normal saline by intraperitoneal injection for six hourly injections in an injection volume of 10 uL per g body weight. LPS 10mg/kg injection was given with the first dose of cererulein. Concurrent with the first and third dose of caerulein, mice were give intraperitoneal injections of sterile saline, 2.5 mM HEPES, pH 7.40 or 320 mM aspartate, 2.5mM HEPES, pH 7.40 at 30uL per g body weight. Mice were sacrificed one hour after the last injection of caerulein with pancreas and serum then harvested for analysis. Markers of inflammation were quantified by using qPCR, ELISA. Pancreatic tissue was fixed in formalin, paraffin embedded, sectioned, and stained with hemotoxylin and eosin. Necrosis and edema was scored as 0-3 for none, 1-25%, 25-50%, or >50% Results: Aspartate supplementation suppresses inflammation in the LPS caerulein hyperstimulation model of acute pancreatitis. Aspartate supplementation at 9.6 uM per gram body weight by intraperitoneal injection with the first and third dose of six hourly intraperitoneal injections of caerulein sulfate at 100 pg per gram body weight significantly decreased serum amylase and pancreatic pro IL-1beta, NLrp3 and pro caspase 1 induction. On hemotoxylin and eosin stain there is decrease of inflammation, necrosis and edema. Conclusion: Aspartate suppresses TLR4 and NLRP3 mediated pro-inflammatory signaling and acute pancreatitis. Aspartic acid has potential as a therapeutic agent in the treatment of acute pancreatitis.