Role of Heparin on TNF-α and IL-6 Levels in Liver Regeneration after Partial Hepatic Resection

Abstract

Objectives: The aim of this study was to investigate the effect of heparin on TNF-α and interleukin (IL)-6 levels and the complement system in liver regeneration in a murine model. Materials and 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 (CH₅₀/ml). On the 5th postoperative day, blood was taken to assess CH₅₀ activity and the levels of TNF-α 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 CH₅₀ activity of group 1 was 4% as compared to 51% in group 3 (p = 0.01). The serum TNF-α 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). Conclusion: Because of its anti-inflammatory action via the complement system, heparin produced an unfavorable effect on liver regeneration.

Branches of the NF-κB signaling pathway regulate proliferation of oval cells in rat liver regeneration

“…The key gene, Tnfrsf12a, was up-regulated at 2-12, 30-36, and 120 h, Ikbkb (inhibitor of kappa light polypeptide gene enhancer in B-cells) was up-regulated at 2, 24-30, and 72 h and the mRNA level of BF419700 (the homologue of transcription factor NF-kB family member RELA) increased at 2, 12-24, and 36-168 h ( Table S1). The results above were consistent with those found by Yuceturk et al (2007). Based on the above results, a possible relationship between the TNF-a branch and oval cell proliferation was proposed as follows; the over-expression of TNF-a and its receptor, TNFRSF12A, activates Ikbkb, leading to the activation of AA998997 (the homologous gene of the transcription factor NF-kB family member RELA).…”

Extent of liver resection modulates the activation of transcription factors and the production of cytokines involved in liver regeneration

“…In particular, the role of proregenerative cytokines (e.g. IL-6 and TNF-a) and the role of transcription factors such as NF-κB are ambiguous [5,[20][21][22] .…”

Vascular Endothelial Growth Factor Improves Liver Regeneration and Survival after 90% Hepatectomy in a Rat Model of Diet-Induced Steatosis

“…Although TNF-α is thought to be an important cytokine for liver regeneration early after hepatectomy [26], excessive TNF-α production between 12 and 24 h after liver resection was considered to be a major determinant of liver failure [12,19,36]. Thus, we would speculate that overproduction of this mediator might be one explanation for the unfavorable effects of EPO in this model leading to impairment of liver regeneration [12,36,37]. However, these discrepant results may also be related to differences in the experimental setting, i.e.…”