Protective effect of leflunomide against oxidative intestinal injury in a rodent model of sepsis

J Surg Res. 2014 Apr;187(2):610-5. doi: 10.1016/j.jss.2013.11.005. Epub 2013 Nov 26.

Abstract

Background: Sepsis is defined as an uncontrolled inflammatory response in a host. The process may lead to severe sepsis, multisystem organ failure and even death. Leflunomide has important immunomodulatory and anti-inflammatory effects, which may mitigate host response to bacterial translocation. The goal of our study was to measure the effects leflunomide administration had on a variety of biochemical markers upregulated in systemic inflammatory response syndrome, sepsis, and multiple organ failure syndrome.

Materials and methods: Wistar albino type rats were randomly divided into five groups: control, sham, leflunomide, sepsis, and sepsis + leflunomide. Sepsis was achieved by means of the cecal ligation and puncture method. Leflunomide 2 × 10 mg/kg/d was administered before the experiment. At the end of 24 h, the tissue levels of superoxide dismutase, catalase activity, malondialdehyde, nitric oxide, and protein carbonyl were measured.

Results: The level of the bowel superoxide dismutase and catalase levels of the sepsis group is significantly lower than those of the control, sham, and leflunomide groups (P < 0.05). Malondialdehyde, nitric oxide, and protein carbonyl levels are significantly higher in sepsis compared with other groups (P < 0.05).

Conclusions: Leflunomide's prevention of protein and lipid peroxidation was observed in septic bowel tissue. Use of leflunomide could have protective effects against both the onset and the progressive stages of sepsis.

Keywords: Leflunomide; Oxidative stress; Sepsis.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
  • Antioxidants / pharmacology*
  • Biomarkers / metabolism
  • Catalase / metabolism
  • Cecum / injuries
  • Disease Models, Animal
  • Intestinal Mucosa / immunology
  • Intestinal Mucosa / metabolism
  • Intestinal Mucosa / pathology
  • Intestines / immunology
  • Intestines / pathology
  • Isoxazoles / pharmacology*
  • Leflunomide
  • Male
  • Malondialdehyde / metabolism
  • Multiple Organ Failure* / drug therapy
  • Multiple Organ Failure* / immunology
  • Multiple Organ Failure* / metabolism
  • Nitric Oxide / metabolism
  • Oxidative Stress / drug effects*
  • Oxidative Stress / immunology
  • Random Allocation
  • Rats
  • Rats, Wistar
  • Sepsis* / drug therapy
  • Sepsis* / immunology
  • Sepsis* / metabolism
  • Superoxide Dismutase / metabolism

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Antioxidants
  • Biomarkers
  • Isoxazoles
  • Nitric Oxide
  • Malondialdehyde
  • Catalase
  • Superoxide Dismutase
  • Leflunomide