Effect of leflunomide on liver regeneration after partial hepatectomy in rats.
OBJECTIVE
Partial hepatectomy (PH) can be an inevitable surgical therapy in some conditions, such as hepatic malignancies, trauma or partial liver transplantation. Its capacity for regeneration distinguishes the liver from other essential organs. Regeneration is a complex process involving growth factors, cytokines, transcription factors, hormones, and oxidative stress products. In the event of ineffective or total absent liver regeneration, the life threatening picture of acute liver failure may supervene. In the present research, we studied the effect of leflunomide, a novel immunosuppressive and antiinflammatory agent against autoimmune disease, on hepatic regeneration after PH in Wistar Albino rats.


METHODS
Thirty-five Wistar albino rats were divided into five groups: group 1, control; group 2, sham; group 3, drug control (was treated with leflunomide 10 mg/kg/d/i.g.); group 4, PH; group 5, PH + leflunomide. As for PH, approximately 70% of the rat liver was surgically removed under general anesthesia. On postoperative day 3, all rats were humanely killed. Catalase (CAT), superooxide dismutase (SOD) and myeloperoxidase (MPO) activities with malondialdehyde (MDA), nitric oxide and protein carbonyl (PC) levels were determined in remnant liver tissue. Inflammatory process and liver regeneration were evaluated with H&E and KI67, respectively.


RESULTS
The tissue levels of MDA, PC and MPO were lower in group 5 than levels in group 1. PH significantly decreased the enzymatic activity of CAT (p < 0.05) and SOD. This reduction was significantly improved by the treatment with leflunomide. Histopathologically the enhancement of the liver parenchymal regeneration in the group 5 was significantly greater than the group 4.


CONCLUSIONS
The findings imply that oxidative stress products play a preventive role in liver regeneration after PH and leflunomide ameliorates the regeneration probably by the radical scavenging and antioxidant activities.
Department of Pediatric Surgery, Faculty of Medicine, Turgut Ozal Medical Center, Inonu University, Malatya, Turkey. akaraman@inonu.edu.tr
Abdurrahman
A
Karaman
Hale
H
Kirimlioglu
Erkan
E
Tas
Nese
N
Karadag
Cebrail
C
Gülsul
Ersin
E
Fadillioglu
Mehmet
M
Demircan
D000276:Adjuvants, Immunologic; D000818:Animals; D002374:Catalase / Q000378:metabolism; D004195:Disease Models, Animal; D006498:Hepatectomy / Q000379:methods*; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007555:Isoxazoles / Q000494:pharmacology*; D000077339:Leflunomide; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000601:surgery; D008107:Liver Diseases / Q000378:metabolism / Q000601:surgery; D008115:Liver Regeneration / Q000187:drug effects* / Q000502:physiology; D008315:Malondialdehyde / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D009195:Peroxidase / Q000378:metabolism; D050050:Protein Carbonylation / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D016896:Treatment Outcome
D000276:Adjuvants, Immunologic; D007166:Immunosuppressive Agents; D007555:Isoxazoles; D009569:Nitric Oxide; D008315:Malondialdehyde; D002374:Catalase; D009195:Peroxidase; D000077339:Leflunomide