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


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.
Department of Anesthesiology and Reanimation, Faculty of Medicine, Bezmialem Vakif University, Istanbul, Turkey. Electronic address: erdoganozturk@gmail.com.
Erdogan
E
Ozturk
Sehit Kamil Devlet Hastanesi, Gaziatep, Turkey.
Murat
M
Surucu
Department of Pediatric Surgery, Faculty of Medicine, Inonu University, Malatya, Turkey.
Abdurrahman
A
Karaman
Department of Pathology, Faculty of Medicine, Inonu University, Malatya, Turkey.
Emine
E
Samdancı
Department of Physiology, Hacettepe University, Ankara, Turkey.
Ersin
E
Fadillioglu
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology*; D015415:Biomarkers / Q000378:metabolism; D002374:Catalase / Q000378:metabolism; D002432:Cecum / Q000293:injuries; D004195:Disease Models, Animal; D007413:Intestinal Mucosa / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D007422:Intestines / Q000276:immunology / Q000473:pathology; D007555:Isoxazoles / Q000494:pharmacology*; D000077339:Leflunomide; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D009102:Multiple Organ Failure / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects* / Q000276:immunology; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D018805:Sepsis / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000975:Antioxidants; D015415:Biomarkers; D007555:Isoxazoles; D009569:Nitric Oxide; D008315:Malondialdehyde; D002374:Catalase; D013482:Superoxide Dismutase; D000077339:Leflunomide
Leflunomide; Oxidative stress; Sepsis