Anti-inflammatory and Antioxidant Effects of Captopril Compared to Methylprednisolone in L-Arginine-Induced Acute Pancreatitis

Dig Dis Sci. 2018 Jun;63(6):1497-1505. doi: 10.1007/s10620-018-5036-1. Epub 2018 Mar 29.

Abstract

Background: Acute pancreatitis (AP) is an inflammatory disease mediated by damage in acinar cells and pancreatic inflammation with infiltration of leukocytes. The pancreatic renin-angiotensin system may play an important role in the pathogenesis of AP.

Aim: The present study aimed to investigate the possible protective role of captopril (CAP), an angiotensin-converting enzyme inhibitor, in attenuating L-arginine-induced AP rat model and to elucidate the underlying molecular mechanisms.

Methods: Forty-eight adult male Wister rats were divided into four equal groups: control group (vehicle, orally for 10 days), AP group (3 g/kg L-arginine, single i.p.) on 10th day of the experiment, CAP group (50 mg/kg captopril, orally, once daily), and MP group (30 mg/kg methylprednisolone, orally, once daily). CAP and MP were administered for 10 days prior to L-arginine injection. Rats were sacrificed 24 h after arginine injection. Inflammatory biomarkers; tumor necrosis factor alpha (TNF-α) concentration, myeloperoxidase (MPO) activity, and inducible nitric oxide synthase (iNOS) gene expression were determined in pancreas. Oxidative stress biomarkers; pancreatic nitric oxide (NO) and reduced glutathione (GSH) concentrations were measured. Moreover, serum α-amylase and lipase activities were measured and histopathological studies of the pancreas were done.

Results: CAP group showed a significant reduction in pancreatic TNF-α concentration, MPO activity, NO concentration, and downregulation of iNOS gene expression compared to AP group. CAP group also showed a significant increase in GSH concentration with amelioration of histological changes of AP as well as MP group.

Conclusion: Captopril treatment showed a protective and comparable effect with MP treatment in AP rat model.

Keywords: Acute pancreatitis; Captopril; Myeloperoxidase; TNF-α; iNOS.

Publication types

  • Comparative Study

MeSH terms

  • Acute Disease
  • Angiotensin-Converting Enzyme Inhibitors / pharmacology*
  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Antioxidants / pharmacology*
  • Arginine*
  • Captopril / pharmacology*
  • Cytoprotection
  • Disease Models, Animal
  • Glutathione / metabolism
  • Lipase / blood
  • Male
  • Methylprednisolone / pharmacology*
  • Nitric Oxide / metabolism
  • Nitric Oxide Synthase Type II / metabolism
  • Pancreas / drug effects*
  • Pancreas / metabolism
  • Pancreas / pathology
  • Pancreatitis / chemically induced
  • Pancreatitis / metabolism
  • Pancreatitis / pathology
  • Pancreatitis / prevention & control*
  • Peroxidase / metabolism
  • Rats, Wistar
  • Renin-Angiotensin System / drug effects*
  • Signal Transduction / drug effects
  • Tumor Necrosis Factor-alpha / metabolism
  • alpha-Amylases / blood

Substances

  • Angiotensin-Converting Enzyme Inhibitors
  • Anti-Inflammatory Agents
  • Antioxidants
  • Tumor Necrosis Factor-alpha
  • Nitric Oxide
  • Arginine
  • Captopril
  • Peroxidase
  • Nitric Oxide Synthase Type II
  • Nos2 protein, rat
  • Lipase
  • alpha-Amylases
  • Glutathione
  • Methylprednisolone