Mesna Alleviates Cerulein-Induced Acute Pancreatitis by Inhibiting the Inflammatory Response and Oxidative Stress in Experimental Rats

Dig Dis Sci. 2020 Dec;65(12):3583-3591. doi: 10.1007/s10620-020-06072-1. Epub 2020 Feb 22.

Abstract

Background: Acute pancreatitis (AP) is a sudden inflammation of the pancreas that may be life-threatening disease with high mortality rates, particularly in the presence of systemic inflammatory response and multiple organ failure. Oxidative stress has been shown to be involved in the pathophysiology of acute pancreatitis.

Aim: This study is designed to investigate the possible effect of mesna on an experimental model of cerulein-induced acute pancreatitis.

Methods: Animals were divided into five groups: Group 1 served as a control group given the saline; group II (mesna group) received mesna at a dose of (100 mg/kg per dose, i.p.) four times; group III (acute pancreatitis group) received cerulein at a dose of (20 µg/kg/dose, s.c.) four times with 1-h intervals; group VI, cerulein + mesna, was treated with mesna at a dose of (100 mg/kg, i.p.) 15 min before each cerulein injection.

Results: Animals with acute pancreatitis showed elevated serum amylase and lipase levels. Biochemical parameters showed increased pancreatic tumor necrosis factors-α (TNF-α) and interleukin-1β (IL-1β) levels. A disturbance in oxidative stress markers was evident by elevated pancreatic lipid peroxides (TBARS) and decline in pancreatic antioxidants' concentrations including reduced glutathione (GSH); superoxide dismutase (SOD); and glutathione peroxidase (GSH-Px). Histological examination confirmed pancreatic injury. Pre-treatment with mesna was able to abolish the changes in pancreatic enzymes, oxidative stress markers (TBARS, SOD, GSH and GSH-Px), pancreatic inflammatory markers (TNF-α, IL-1β) as well as histological changes.

Conclusions: Mesna mitigates AP by alleviating pancreatic oxidative stress damage and inhibiting inflammation.

Keywords: 2-Mercaptoethane sulfonate sodium (MESNA); Acute pancreatitis; Cerulein; Inflammation; Oxidative injury.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antioxidants / analysis
  • Ceruletide / pharmacology*
  • Cholagogues and Choleretics / pharmacology
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Interleukin-1beta / blood
  • Mesna* / metabolism
  • Mesna* / pharmacology
  • Oxidative Stress / drug effects*
  • Pancreas* / drug effects
  • Pancreas* / enzymology
  • Pancreas* / pathology
  • Pancreatitis* / chemically induced
  • Pancreatitis* / metabolism
  • Pancreatitis* / prevention & control
  • Protective Agents / metabolism
  • Protective Agents / pharmacology
  • Rats
  • Treatment Outcome
  • Tumor Necrosis Factor-alpha / blood

Substances

  • Antioxidants
  • Cholagogues and Choleretics
  • Interleukin-1beta
  • Protective Agents
  • Tumor Necrosis Factor-alpha
  • Ceruletide
  • Mesna