Niclosamide as a Prospective Therapeutic in L-Arginine Induced Acute Pancreatitis in Rats; Concerning Autophagic p62/ NF-kB signaling pathway

Autophagic flux impairment is recently reported as a cardinal factor in acute pancreatitis (AP)pathogenesis. Niclosamide, an anthelmintic drug, has been lately proved to be a potent autophagyenhancer. The diminution of the various inflammatory factors unrestrained release via autophagyimprovement may be helpful to improve the prognosis of AP. This study spots on investigating thepotential ameliorative effect of niclosamide on autophagic flux and its consequent curative outcomeon L-arginine-induced AP in rats. Thirty male wistar rats were divided into three groups. The first oneis the control one, the second is L-arginine induced AP group, the third group is niclosamide treatedL-arginine induced AP. Serum lipase, amylase, pancreatic tissue homogenate IL6, IL1β, TNFα, NF-kB,oxidative stress biomarkers; glutathione peroxidase activity, Hydroxy-2’-Deoxy-Guanosine and totalantioxidant capacity levels were evaluated. Besides, the DNA-binding activity of nuclear erythroidrelated factor 2 (Nrf-2) was assessed using a pancreatic tissue nuclear extract. Both LC3-II subunit &P62 mRNA were quantified using PCR technique. Morphometric analysis of histopathological changeswas done. The obtained data showed that niclosamide improved L-arginine induced AP as evidencedby significantly reduced serum lipase and amylase levels, which could be related to improvement ofautophagy flux impairment as evidenced by decreased levels of LC3-II and p62 expression in pancreaticcells, in addition to anti-inflammatory effect as evidenced by decreased NF-kB and proinflammatorycytokines levels, along with improving the antioxidant capacity of the pancreatic tissue. As manifestedby elevation of Nrf-2- DNA binding activity and normalization of oxidative stress biomarkers levels.These results could pave the way for niclosamide as a potential therapeutic role in acute pancreatitis.