Influence of Telomere Length in Hepatocytes on Liver Regeneration after Partial Hepatectomy in Rats

2018 ◽  
Vol 59 (1-2) ◽  
pp. 83-90 ◽  
Author(s):  
Anne Andert ◽  
Hamid P. Alizai ◽  
Tom Florian Ulmer ◽  
Christoph Heidenhain ◽  
Patrick Ziegler ◽  
...  
Keyword(s):  
Liver Regeneration ◽  
Telomere Length ◽  
Partial Hepatectomy ◽  
Rat Hepatocytes ◽  
Liver Weight ◽  
Nuclear Antigen ◽  
Hepatic Regeneration ◽  
Older Individuals ◽  
Significant Difference ◽  
Old Rats

Background: The aim of this study was to investigate telomere length in hepatocytes as a biomarker for liver regeneration after partial hepatectomy (PH) in rats. Materials and Methods: Sixty male Wistar rats underwent a 70% PH. One-month-old rats were assigned to group Y (n = 30) and 4-month-old rats were assigned to group O (n = 30). The rats were euthanized, and their livers were then harvested at postoperative day (POD) 1, 2, 3, 4, or 7. Telomere lengths and established parameters for liver regeneration (residual liver weight and levels of proliferating cell nuclear antigen [PCNA], Ki67, and interleukin [IL]-6) were measured. Results: We observed a significant increase in residual liver weight in group Y compared to that in group O (p = 0.001). The levels of Ki67 (p = 0.016), PCNA (p < 0.0001), and IL-6 (p < 0.001) were significantly higher in group Y. Furthermore, the rats in group Y had significantly earlier peak values of Ki67 and PCNA. Telomeres were significantly longer at the time of PH in group Y (p = 0.001). We showed a correlation between telomere length at the day of PH and liver regeneration. Animals with longer telomeres at the time of PH had better liver regeneration (p = 0.015). In group Y, animals with increased liver regeneration (median cut-off: > 122%) did not show any significant difference in telomere length (p = 0.587) compared to rats with regular regeneration (< 122%). However, in the older animals, rats with increased regeneration had significantly longer telomeres (p = 0.019) than rats with regular regeneration. Conclusion: Telomere length in rat hepatocytes depends on age, and animals with long telomeres had earlier and better regeneration of healthy liver tissue than rats with short telomeres. Our data confirms that telomere length in rat hepatocytes could be used as a possible predictive marker for liver regeneration, and could help to identify older individuals with a high capacity for hepatic regeneration.

scholarly journals Effect of the aqueous extract of Sida cordifolia on liver regeneration after partial hepatectomy

2006 ◽  
Vol 21 (suppl 1) ◽  
pp. 37-39 ◽  
Author(s):  
Renata Lemos Silva ◽  
Gustavo Barreto de Melo ◽  
Valdinaldo Aragão de Melo ◽  
Ângelo Roberto Antoniolli ◽  
Paulo Roberto Teixeira Michellone ◽  
...  
Keyword(s):  
Oral Administration ◽  
Liver Regeneration ◽  
Partial Hepatectomy ◽  
Aqueous Extract ◽  
Proliferating Cell Nuclear Antigen ◽  
Nuclear Antigen ◽  
Hepatic Regeneration ◽  
Control Group ◽  
Sida Cordifolia ◽  
Proliferating Cell

PURPOSE: The use of medicinal plants for the treatment of human diseases has increased worldwide. Many of them are used by oral administration and, after absorption, may affect many organs. Therefore, this study aimed at assessing the effects of the aqueous extract of Sida cordifolia leaves, popularly known in Brazil as "malva-branca", on liver regeneration. METHODS: Twenty rats were divided into four groups: control, Sida100, Sida200 and Sida400 groups. All animals were submitted to oral administration of distilled water, 100, 200 and 400 mg/kg of the aqueous extract of Sida cordifolia, respectively. Immediately after this, they underwent 67% partial hepatectomy. Twenty four hours later, their livers were removed. Hepatic regeneration was assessed by immunohistochemical staining for proliferating cell nuclear antigen (PCNA) using the PC-10 monoclonal antibody. RESULTS: Sida100 and Sida200 groups disclosed higher liver regeneration indices than control group (p<0.001 and p<0.05, respectively). CONCLUSION: The aqueous extract of Sida cordifolia stimulates liver regeneration after 67% partial hepatectomy in rats.

scholarly journals Resina Draconis Reduces Acute Liver Injury and Promotes Liver Regeneration after 2/3 Partial Hepatectomy in Mice

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Zhi-yong He ◽  
Kai-han Lou ◽  
Jia-hui Zhao ◽  
Ming Zhang ◽  
Lan-chun Zhang ◽  
...  
Keyword(s):  
Liver Injury ◽  
Liver Regeneration ◽  
Partial Hepatectomy ◽  
Acute Liver Injury ◽  
Liver Weight ◽  
Nuclear Antigen ◽  
Protective Effects ◽  
Weight Restoration ◽  
Resina Draconis ◽  
Proliferating Cell

Aim. To investigate the protective effects and possible mechanisms of action of resina draconis (RD) on acute liver injury and liver regeneration after 2/3 partial hepatectomy (PH) in mice. Methods. 2/3 PH was used to induce acute liver injury. Mice were divided into three groups: sham, vehicle + 2/3 PH, and RD + 2/3 PH. Resina draconis was administered intragastrically after 2/3 PH into the RD + 2/3 PH group, and the same volume of vehicle (1% sodium carboxymethyl cellulose) was injected into the vehicle + 2/3 PH group and sham group mice. The index of liver to body weight (ILBW) and proliferating cell nuclear antigen (PCNA) were assayed to evaluate liver regeneration. Blood and liver tissues were collected for serological and western blotting analysis. Results. Resina draconis protected against 2/3 PH-induced acute severe liver injury and promoted liver regeneration as shown by significantly increased ILBW compared with that of controls. 2/3 PH increased serum AST and ALT levels, which were significantly decreased by RD treatment, while 2/3 PH decreased serum TP and ALB, which were increased by RD treatment. In the RD + 2/3 PH group, PCNA expression was significantly increased compared with the 2/3 PH group. Further, hepatocyte growth factor (HGF), TNFα, and EGFR levels were increased in the RD group at postoperative days 2 and 4 compared with the those in the 2/3 PH group. Conclusion. Our results suggest that RD ameliorates acute hepatic injury and promotes liver cell proliferation, liver weight restoration, and liver function after 2/3 PH, probably via HGF, TNFα, and EGFR signaling.

Polyamines are required for the initiation of rat liver regeneration

2002 ◽  
Vol 362 (1) ◽  
pp. 149-153 ◽  
Author(s):  
Leena ALHONEN ◽  
Tiina-Liisa RÄSÄNEN ◽  
Riitta SINERVIRTA ◽  
Jyrki J. PARKKINEN ◽  
Veli-Pekka KORHONEN ◽  
...  
Keyword(s):  
Weight Gain ◽  
Liver Regeneration ◽  
Partial Hepatectomy ◽  
Transgenic Animals ◽  
Liver Weight ◽  
Labelling Index ◽  
Nuclear Antigen ◽  
Leucine Incorporation ◽  
Transgenic Rats ◽  
Liver Remnant

A large number of studies applying inhibitors of polyamine biosynthesis have indicated that these compounds are required for animal cell proliferation. Here we show, using a transgenic rat model with activated polyamine catabolism, that a certain critical concentration of the higher polyamines spermidine and spermine is required for liver regeneration. Partial hepatectomy of transgenic rats expressing spermidine/spermine N1-acetyltransferase (SSAT) under the control of mouse metallothionein promoter strikingly induced the enzyme at 24h and reduced hepatic spermidine by 80%. At that time, the weight of the liver remnant was significantly increased in syngenic rats and proliferating cell nuclear antigen (PCNA) labelling index was 20%, whereas the transgenic rats showed no liver weight gain and their PCNA-positive cells accounted for 0.5% of hepatocytes. Similarly, hepatic thymidine incorporation was markedly enhanced at this time point in syngenic, but not in transgenic, animals, whereas the rate of leucine incorporation was only marginally affected in the transgenic animals. At 3 days after operation, the spermidine pool in transgenic livers had increased to the pre-operative level, the remnant weight was significantly elevated and hepatic PCNA labelling index increased to 5%. N1,N11-Diethylnorspermine, a powerful inducer of SSAT, inhibited liver weight gain and proliferative activity in both syngenic and transgenic rats. We found an extremely close correlation between hepatic spermidine, and less close between spermine, concentrations and PCNA labelling index during early liver regeneration. These results indicate that spermidine and/or spermine, but apparently not putrescine, are required for liver regeneration, yet at concentrations smaller than those normally found after partial hepatectomy.

scholarly journals Cerium oxide nanoparticles improve liver regeneration after acetaminophen-induced liver injury and partial hepatectomy in rats

2019 ◽  
Vol 17 (1) ◽  
Author(s):  
Bernat Córdoba-Jover ◽  
Altamira Arce-Cerezo ◽  
Jordi Ribera ◽  
Montse Pauta ◽  
Denise Oró ◽  
...  
Keyword(s):  
Liver Injury ◽  
Liver Regeneration ◽  
Cerium Oxide ◽  
Partial Hepatectomy ◽  
Experimental Models ◽  
Cerium Oxide Nanoparticles ◽  
Hepatic Regeneration ◽  
Oxide Nanoparticles ◽  
Acetyl Cysteine

Abstract Background and aims Cerium oxide nanoparticles are effective scavengers of reactive oxygen species and have been proposed as a treatment for oxidative stress-related diseases. Consequently, we aimed to investigate the effect of these nanoparticles on hepatic regeneration after liver injury by partial hepatectomy and acetaminophen overdose. Methods All the in vitro experiments were performed in HepG2 cells. For the acetaminophen and partial hepatectomy experimental models, male Wistar rats were divided into three groups: (1) nanoparticles group, which received 0.1 mg/kg cerium nanoparticles i.v. twice a week for 2 weeks before 1 g/kg acetaminophen treatment, (2) N-acetyl-cysteine group, which received 300 mg/kg of N-acetyl-cysteine i.p. 1 h after APAP treatment and (3) partial hepatectomy group, which received the same nanoparticles treatment before partial hepatectomy. Each group was matched with vehicle-controlled rats. Results In the partial hepatectomy model, rats treated with cerium oxide nanoparticles showed a significant increase in liver regeneration, compared with control rats. In the acetaminophen experimental model, nanoparticles and N-acetyl-cysteine treatments decreased early liver damage in hepatic tissue. However, only the effect of cerium oxide nanoparticles was associated with a significant increment in hepatocellular proliferation. This treatment also reduced stress markers and increased cell cycle progression in hepatocytes and the activation of the transcription factor NF-κB in vitro and in vivo. Conclusions Our results demonstrate that the nanomaterial cerium oxide, besides their known antioxidant capacities, can enhance hepatocellular proliferation in experimental models of liver regeneration and drug-induced hepatotoxicity.

scholarly journals Rat Hepatocytes Weighted Gene Co-Expression Network Analysis Identifies Specific Modules and Hub Genes Related to Liver Regeneration after Partial Hepatectomy

PLoS ONE ◽  
2014 ◽  
Vol 9 (4) ◽  
pp. e94868 ◽  
Author(s):  
Yun Zhou ◽  
Jiucheng Xu ◽  
Yunqing Liu ◽  
Juntao Li ◽  
Cuifang Chang ◽  
...  
Keyword(s):  
Network Analysis ◽  
Liver Regeneration ◽  
Partial Hepatectomy ◽  
Rat Hepatocytes ◽  
Hub Genes

Polyamine transport systems in isolated rat hepatocytes derived from resting and regenerating livers

1992 ◽  
Vol 263 (2) ◽  
pp. G169-G173
Author(s):  
G. Y. Minuk ◽  
A. Bennaroch ◽  
L. X. Ding
Keyword(s):  
Partial Hepatectomy ◽  
Specific Binding ◽  
Rat Hepatocytes ◽  
Eukaryotic Cell ◽  
Transport Systems ◽  
Affinity Constant ◽  
Hepatic Regeneration ◽  
Gamma Aminobutyric Acid ◽  
Isolated Rat Hepatocytes ◽  
Polyamine Transport

Polyamines and their principal metabolite, gamma-aminobutyric acid (GABA), modulate eukaryotic cell growth. To determine whether the liver possesses specific polyamine transport sites and whether changes occur to these or GABA transport sites during hepatic regeneration, suspensions of rat hepatocytes derived from in situ collagenase perfusions of livers at times 0, 24, 48, and 72 h post-partial hepatectomy were incubated at 4, 20, and 37 degrees C with various concentrations of the following ligands: [3H]putrescine, [3H]spermidine, [14C]spermine, and [3H]GABA together with or without excess unlabeled ligand, KCN, ouabain, or digitoxigenin. Of the ligands studied, only [14C]spermine and [3H]GABA were associated with specific binding to hepatocytes derived from nonregenerating livers. Spermine binding correlated with the concentration of hepatocytes in the incubation mixture and reached equilibrium within 60 min. The approximate affinity constant (KD) was 5.5 x 10(-5) mol/10(6) hepatocytes, and maximum number of binding sites (Bmax) was 1.8 +/- 1.2 x 10(-7) mol.10(6) hepatocytes-1.min-1. Binding was neither temperature nor sodium dependent and was not inhibited by KCN, ouabain, digitoxigenin, other polyamines, or GABA. Aside from a 43% decrease in spermine binding at 24 h post-partial hepatectomy [5.1 +/- 1.1 vs. 8.9 +/- 3.1 x 10(3) disintegrations per minute (dpm)/10(6) hepatocytes at time 0, P less than 0.05] and a 39% decrease in GABA binding (3.4 +/- 1.3 vs. 5.5 +/- 1.9 x 10(3) dpm/10(6) hepatocytes, P less than 0.05), there were no significant changes in ligand binding during hepatic regeneration.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Proliferative effect of aqueous extract of Hyptis fructicosa on liver regeneration after partial hepatectomy in rats

2012 ◽  
Vol 27 (1) ◽  
pp. 71-75 ◽  
Author(s):  
Sônia Oliveira Lima ◽  
Luciano da Costa Viana ◽  
Fábio Rafael Teixeira de Santana ◽  
Ségio Zucoloto ◽  
Ricardo Luiz de Albuquerque Junior ◽  
...  
Keyword(s):  
Liver Regeneration ◽  
Partial Hepatectomy ◽  
Aqueous Extract ◽  
Hepatocyte Proliferation ◽  
Hepatic Regeneration ◽  
Control Group ◽  
Immunohistochemical Technique ◽  
Proliferative Effect

PURPOSE: To evaluate the effect of aqueous extract of Hyptis fructicosa on hepatic regeneration after partial hepatectomy in rats. METHODS: Sixteen rats were divided in two groups: C (Control Group) and HF (Whose rats received aqueous extract of Hyptis fructicosa during 4 days using the dose of 100 mg/kg/day). On the consecutive day of this treatment, the animals of both groups underwent hepatectomy of about 67% of liver. Twenty four hours later, they were sacrificed, and the remaining mass of liver was removed and prepared to be studied through the PCNA immunohistochemical technique. RESULTS: The liver regeneration index of HF group was 53.56 ± 18.91%, while in C group was 21.12 ± 8.29% (p=0.0003). CONCLUSION: These results show that the administration of aqueous extract of Hyptis fructicosa using the dose of 100mg/kg/day increased the hepatocyte proliferation in the group HF.

scholarly journals Effect of vitamin C on liver regeneration after partial hepatectomy and acetaminophen-induced liver injury in Wistar rats

2021 ◽  
Vol 8 (2) ◽  
pp. 489
Author(s):  
Reno Rudiman ◽  
Handy Wing ◽  
Nurhayat Usman
Keyword(s):  
Lipid Peroxidation ◽  
Liver Injury ◽  
Vitamin C ◽  
Liver Regeneration ◽  
Partial Hepatectomy ◽  
Wistar Rats ◽  
Liver Weight ◽  
Potential Effect ◽  
Regeneration Rate ◽  
Male Wistar Rats

Background: The aim of this study is to evaluate the potential effect of vitamin C as an antioxidant on liver regeneration after partial hepatectomy and acetaminophen-induced liver injury in Wistar rats.Methods: A total of 24 male Wistar rats were divided into four groups, each group consisted of 6 rats: group A (control, partial hepatectomy/PHx alone), group B (PHx and vitamin C 250 mg/kg BW), group C (acetaminophen 500 mg/kg BW and PHx), and group D (acetaminophen 500 mg/kg BW with PHx and vitamin C 250 mg/kg BW). Subtoxic dose of acetaminophen was given 24 hours before partial hepatectomy. Vitamin C was given orally via oral gavage for 6 consecutive days after partial hepatectomy. POD 7, all animals were terminated and performed laparotomy to obtain liver tissue for measurement of liver weight and regeneration rate, blood samples for malondialdehyde (MDA) as a lipid peroxidation measurement and histopathological investigation.Results: The means of regeneration rate in vitamin C groups were significantly higher compared to non-vitamin C group (p<0.05). Similar result, the means of MDA values in vitamin C groups were significantly lower compared to non-vitamin C group (p<0.05). This result suggests a protective effect of vitamin C against lipid peroxidation. Histopathological changes in liver cells were statistically difference between vitamin C groups and non-vitamin C groups (p<0.05).Conclusions: Our results indicate that vitamin C administration promotes liver regeneration and inhibits lipid peroxidation after partial hepatectomy and acetaminophen-induced liver injury in Wistar rats.

scholarly journals EFFECTS OF LOW-LEVEL LASER THERAPY ON LIVER REGENERATION AND THE LASER PARAMETERS EMPLOYED

2021 ◽  
Vol 25 (3) ◽  
Author(s):  
Fernando De Santana Belli Rodrigues ◽  
Gisele Lopes Bertolini
Keyword(s):  
Liver Regeneration ◽  
Laser Therapy ◽  
Partial Hepatectomy ◽  
Low Level Laser Therapy ◽  
Therapeutic Window ◽  
Hepatic Regeneration ◽  
Low Level ◽  
Laser Parameters ◽  
Low Level Laser ◽  
Level Laser

Low-level laser therapy has various biological effects; one of them is tissue regeneration. Its application in the liver of rats after partial hepatectomy to promote liver regeneration has recently been studied. The aim of this article was to review the recent studies on the effects of low-level laser therapy on rat liver regeneration after partial hepatectomy and the laser parameters used. A review of recent relevant literature was performed in Pubmed, Scielo, Medline and Bireme databases. Articles about the application of low-level laser therapy on hepatic regeneration were included. Articles with hepatic regeneration in the presence of pathologies were not included. Nine studies were found matching the study criteria. In most studies, low-level laser therapy promoted liver regeneration after partial hepatectomy, without further damage to the remaining liver. Not all laser parameters necessary for the reproducibility of the study were described by all authors. The therapeutic use of low-level laser therapy in liver regeneration can be promising, however, as liver is a vital organ and the laser application is intraoperative, future studies are needed. The parameters used must be properly described and standardized to allow the reproducibility of the study, so that a therapeutic window can be defined and its clinical use can be considered. It is also essential to clarify the mechanisms by which the laser promotes liver regeneration, to guarantee its safety and therapeutic efficacy.

Antibodies to tumor necrosis factor-alpha inhibit liver regeneration after partial hepatectomy

1992 ◽  
Vol 263 (4) ◽  
pp. G579-G585 ◽  
Author(s):  
P. Akerman ◽  
P. Cote ◽  
S. Q. Yang ◽  
C. McClain ◽  
S. Nelson ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Liver Regeneration ◽  
Partial Hepatectomy ◽  
Tumor Necrosis ◽  
Thymidine Incorporation ◽  
Polyclonal Antibodies ◽  
Male Rats ◽  
Nuclear Antigen ◽  
Necrosis Factor Alpha ◽  
Necrosis Factor

Certain cytokines that are produced in liver may act as growth factors to facilitate wound healing and, hence, may influence liver regeneration. However, this hypothesis has not been directly tested. To determine whether the cytokine response evoked by partial hepatectomy (PH) modulates the process of liver regeneration, adult male rats were injected intraperitoneally with either goat polyclonal antibodies to rat tumor necrosis factor (TNF; 15 micrograms/g body wt) or an equal amount of goat anti-rat immunoglobulin G 1 h before PH. Animals were killed at 12, 24, 48, or 72 h post-PH, 1 h after injection with [3H]thymidine. Serum TNF levels were measured with the L929 cytotoxicity assay, titers of antibody to TNF were determined by enzyme-linked immunoabsorbent assay, and interleukin-6 (IL-6) concentrations were measured by B9 cell bioassay. Liver regeneration was assessed by [3H]thymidine incorporation into hepatic DNA and by immunohistochemical evidence of proliferating cell nuclear antigen (PCNA) expression. Antibodies to TNF were detected in treated rats but not in controls. Titers were highest at 12 h and progressively fell. Although TNF was never detected in serum, treatment with anti-TNF pre-PH significantly inhibited increases in serum IL-6 concentration post-PH. Anti-TNF pretreatment also inhibited [3H]thymidine incorporation into DNA, as well as expression of PCNA by both hepatocytes and liver nonparenchymal cells. These data indicate that TNF positively modulates liver regeneration after PH.

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