Role of heparin on TNF-alpha and IL-6 levels in liver regeneration after partial hepatic resection.
OBJECTIVE
The aim of this study was to investigate the effect of heparin on TNF-alpha and interleukin (IL)-6 levels and the complement system in liver regeneration in a murine model.


METHODS
32 Wistar albino female rats weighing between 180 and 250 g were included in the study. The rats were divided into four groups as follows: group 1, treated with partial (50%) hepatectomy and intravenous heparin 1,000 IU/kg in repeated daily doses; group 2, treated with sham operation and intravenous heparin 1,000 IU/kg in repeated daily doses; group 3, treated with partial (50%) hepatectomy, and group 4 (controls), treated with only sham operation. Before the surgical intervention and after a general anesthetic had been administered to all rats, blood was taken from the left ventricle of each rat, and each sample was assessed to determine total complement hemolytic activity (CH(50)/ml). On the 5th postoperative day, blood was taken to assess CH(50) activity and the levels of TNF-alpha and IL-6 via ELISA. Each rat was then killed by decapitation after which gravimetric analysis and immunohistochemical staining for proliferating cell nuclear antigen (PCNA) were performed.


RESULTS
Serum CH(50) activity of group 1 was 4% as compared to 51% in group 3 (p = 0.01). The serum TNF-alpha level of group 1 was 43 pg/ml as compared to 86 pg/ml in group 3 (p = 0.002). The serum IL-6 level of group 1 was 19 pg/ml as compared to 44 pg/ml in group 3 (p = 0.02). The serum IL-6 level of group 2 was 4 pg/ml as compared to 44 pg/ml in group 3 (p = 0.005). According to the results of gravimetric analysis, the mean regeneration rate of group 1 was 4.4% as compared to 22% of group 3 (p = 0.001). The mean PCNA index values of group 2 was the highest of all groups (p = 0.01). However, the mean PCNA index value of group 1 was the lowest of all groups (p = 0.01).


CONCLUSIONS
Because of its anti-inflammatory action via the complement system, heparin produced an unfavorable effect on liver regeneration.
Yuceturk
H
H
Department of Gastroenterology, Baskent University Faculty of Medicine, Ankara, Turkey.
Yagmurdur
M C
MC
Gur
G
G
Demirbilek
M
M
Bilezikci
B
B
Turan
M
M
Karakayali
H
H
Haberal
M
M
D000818:Animals; D000925:Anticoagulants / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D003165:Complement System Proteins / Q000378:metabolism; D005260:Female; D006493:Heparin / Q000494:pharmacology*; D006498:Hepatectomy; D022781:Hepatocytes / Q000166:cytology / Q000502:physiology; D015850:Interleukin-6 / Q000097:blood*; D008115:Liver Regeneration / Q000187:drug effects* / Q000502:physiology; D023421:Models, Animal; D051381:Rats; D017208:Rats, Wistar; D014409:Tumor Necrosis Factor-alpha / Q000097:blood*
D000925:Anticoagulants; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D006493:Heparin; D003165:Complement System Proteins