Acceleration of Remnant Liver Regeneration After Hepatectomy
Abstract
Objective: Remnant liver tissue is essential for the surgery of primary liver tumors, metastasectomy, or donor hepatectomy. We aimed to determine whether an effective supportive treatment can improve the safety of donors with insufficient remnants and expand the donor pool in countries where LDLT is performed intensively. Therefore, our study investigated the effects of various substance extracts on the regenerative capacity of residual liver tissue following hepatectomy.
Methods: Rats of equal age and approximately equal weight were grouped into 6 groups: Sham, Genabilic acid, Silymarin+curcumin, Ganoderma lucidum, Mixture containing group B vitamins, amino acids, l-carnitine, and sugars, and Phenoxy-2-methyl-2-propionic acid. Subjects' mTOR, insulin, nesfatin, and leptin levels were checked. PCNA was performed for regeneration control, and immunohistochemistry for Ki-67, mTOR, VEGF, FGF, HGF, and Calpain-10 was performed on the liver.
Results: In comparisons between the Sham group and the other groups, there were significant differences for insulin in group 4 (p=0.041) and for nesfatin in group 3 (p<0.001). The other markers were similar. PCNA, Ki-67, mTOR, and Calpain-10 differed significantly across all groups (p < 0.001). It was also significantly different with respect to VEGF, FGF, and HGF compared with the other groups, except for group 4.
Conclusions: It was determined that the silymarin-curcumin was more successful in suppressing hunger hormones. Since liver regeneration with fibrosis is undesirable, although Ganoderma lucidum is thought not to affect FGF levels, it may promote healthier regenerative tissue; however, this has not been demonstrated by immunostaining.
Keywords
Supporting Institution
Project Number
Ethical Statement
References
- Leclercq IA, Vansteenberghe M, Lebrun VB, VanHul NK, Abarca-Quinones J, Sempoux CL, et al. Defective hepatic regeneration after partial hepatectomy in leptin-deficient mice is not rescued by exogenous leptin. Lab Invest. 2006;86(11):1161-71. doi:10.1038/labinvest.3700474.
- Fouraschen SMG, de Ruiter PE, Kwekkeboom J, de Bruin RW, Kazemier K, Metselaar HJ, et al. mTOR signaling in liver regeneration: rapamycin combined with growth factor treatment. World J Transplant. 2013;3(3):36-47. doi:10.5500/wjt.v3.i3.36.
- Lund J, Lassen JB. Elimination and distribution of menbutone (Genabil) in rats. Acta Pharmacol Toxicol. 1969;27(6):429-38. doi:10.1111/j.1600-0773.1969.tb00490.x.
- Yilmaz İ, Hatipoğlu HS, Taşlıdere E, Karaaslan M. Comparing the regenerative effects of silymarin and apricot on liver regeneration after partial hepatectomy in rats. Biomedical Research. 2018;29(7):1465-73. doi:10.4066/biomedicalresearch.29-17-2142.
- Kocaman N, Dabak DÖ. Hepatoprotektif bir ajan: silymarin. Fırat Med J. 2015;20(3):128-32.
- Gillessen A, Schmidt HHJ. Silymarin as supportive treatment in liver diseases: a narrative review. Adv Ther. 2020;37:1279-301. doi:10.1007/s12325-020-01251-y.
- Cetinkunar S, Tokgoz S, Bilgin BC, Erdem H, Aktimur R, Can S, et al. The effect of silymarin on hepatic regeneration after partial hepatectomy: is silymarin effective in hepatic regeneration? Int J Clin Exp Med. 2015;8(2):2578-85. PMCID: PMC4402851.
- Qin L, Qin J, Zhen X, Yang K, Huang L. Curcumin protects against hepatic stellate cells activation and migration by inhibiting the CXCL12/CXCR4 biological axis in liver fibrosis: a study in vitro and in vivo. Biomed Pharmacother. 2018;101:599–607. doi:10.1016/j.biopha.2018.02.091.
Details
Primary Language
English
Subjects
Gastroenterology Surgery, General Surgery, Gastroenterology and Hepatology
Journal Section
Research Article
Authors
Şencan Acar
*
0000-0001-8086-0956
Türkiye
Hüseyin Çakıroğlu
0000-0002-3445-6060
Türkiye
Erdem Çokluk
0000-0002-6205-5109
Türkiye
Özcan Budak
0009-0009-5374-4795
Türkiye
Murat Coşkun
0000-0002-6361-913X
Türkiye
Early Pub Date
June 30, 2026
Publication Date
June 30, 2026
Submission Date
February 10, 2026
Acceptance Date
May 25, 2026
Published in Issue
Year 2026 Volume: 16 Number: 2