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

Authors

  • Heba A. Mahmoud
  • Rowida Raafat Ibrahim
  • Remon S Estfanous
  • Rasha Osama El-Esawy

DOI:

https://doi.org/10.37506/ijfmt.v16i1.17557

Keywords:

Acute Pancreatitis; Niclosamide; autophagy; LC3-II; P62; Nrf-2.

Abstract

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 autophagy
enhancer. The diminution of the various inflammatory factors unrestrained release via autophagy
improvement may be helpful to improve the prognosis of AP. This study spots on investigating the
potential ameliorative effect of niclosamide on autophagic flux and its consequent curative outcome
on L-arginine-induced AP in rats. Thirty male wistar rats were divided into three groups. The first one
is the control one, the second is L-arginine induced AP group, the third group is niclosamide treated
L-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 total
antioxidant capacity levels were evaluated. Besides, the DNA-binding activity of nuclear erythroid
related 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 changes
was done. The obtained data showed that niclosamide improved L-arginine induced AP as evidenced
by significantly reduced serum lipase and amylase levels, which could be related to improvement of
autophagy flux impairment as evidenced by decreased levels of LC3-II and p62 expression in pancreatic
cells, in addition to anti-inflammatory effect as evidenced by decreased NF-kB and proinflammatory
cytokines levels, along with improving the antioxidant capacity of the pancreatic tissue. As manifested
by 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.

Author Biographies

Heba A. Mahmoud

Assistant Professor, Pharmacology Department, Tanta University, Egypt

Rowida Raafat Ibrahim

Assistant Professor, Medical Biochemistry & Molecular Biology, Tanta University, Egypt

Remon S Estfanous

Assistant Professor, Anatomy & Embryology Department Tanta University, Egypt

Rasha Osama El-Esawy

Lecturer, Pharmacology Department, Faculty of Medicine, Tanta University, Egypt

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Published

2021-11-30

How to Cite

Heba A. Mahmoud, Rowida Raafat Ibrahim, Remon S Estfanous, & Rasha Osama El-Esawy. (2021). Niclosamide as a Prospective Therapeutic in L-Arginine Induced Acute Pancreatitis in Rats; Concerning Autophagic p62/ NF-kB signaling pathway. Indian Journal of Forensic Medicine & Toxicology, 16(1), 576–588. https://doi.org/10.37506/ijfmt.v16i1.17557