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 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.

Inhibition of increases in ornithine decarboxylase and putrescine has no effect on rat liver regeneration

1992 ◽  
Vol 262 (4) ◽  
pp. G677-G684
Author(s):  
H. S. Beyer ◽  
M. Ellefson ◽  
M. Stanley ◽  
L. Zieve
Keyword(s):  
Liver Regeneration ◽  
Partial Hepatectomy ◽  
Ornithine Decarboxylase ◽  
Liver Weight ◽  
Leucine Incorporation ◽  
Irreversible Inhibitor ◽  
Polyamine Synthesis ◽  
Total Dna ◽  
Mitotic Figures ◽  
And Control

Polyamines are considered critical for cell proliferation. During liver regeneration in the rat, ornithine decarboxylase (ODC) mRNA and enzyme activity and polyamines (primarily putrescine and spermidine) are known to increase substantially. We examined the effect of inhibition of polyamine synthesis with alpha-difluoromethylornithine (DFMO), an irreversible inhibitor of the ODC enzyme, on regenerating liver weight and total DNA, RNA, and protein, [3H]thymidine and [14C]leucine incorporation, number of mitotic figures, and putrescine, spermidine, and spermine contents. Rats received DFMO beginning 4 days before or immediately after two-thirds partial hepatectomy. In control rats, ODC activity, putrescine, and spermidine increased significantly during regeneration, whereas spermine was unchanged. In rats receiving DFMO, ODC and putrescine changed minimally but spermidine increased as usual. Spermine levels were modestly higher in rats receiving DFMO beginning 4 days before partial hepatectomy. However, despite ODC inhibition and substantially lower levels of putrescine, the course of liver regeneration in rats treated with DFMO was not affected. Total liver mass, DNA, RNA, and protein increased over 5 days equally in rats receiving DFMO and control rats. In addition, there were no differences in [3H]thymidine incorporation into DNA, [14C]leucine incorporation into protein or mitotic indexes between DFMO-treated and control rats at 24 and 48 h after partial hepatectomy. These results suggest that the well-known increases in ODC activity and polyamines that occur during regeneration are not required for liver to undergo its proliferative response to partial hepatectomy.

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 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.

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.

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

2006 ◽  
Vol 21 (suppl 1) ◽  
pp. 33-36 ◽  
Author(s):  
Gustavo Barreto Melo ◽  
Renata Lemos Silva ◽  
Valdinaldo Aragão Melo ◽  
Ângelo Roberto Antoniolli ◽  
Paulo Roberto Teixeira Michellone ◽  
...  
Keyword(s):  
Liver Regeneration ◽  
Partial Hepatectomy ◽  
Aqueous Extract ◽  
Proliferating Cell Nuclear Antigen ◽  
Serum Enzymes ◽  
Nuclear Antigen ◽  
Proliferative Effect ◽  
Water Administration ◽  
Proliferating Cell ◽  
Hepatic Protection

PURPOSE: This study was carried out to assess the effects of the aqueous extract of Hyptis pectinata leaves on liver regeneration and on serum enzymes (AST, ALT and gamma-GT) after 67% partial hepatectomy in rats. METHODS: AST, ALT and gamma-GT, were determined by conventional procedures using a spectrophotometer (Model E2250-CELM). Liver regeneration was evaluated by immunohistochemical staining for proliferating cell nuclear antigen (PCNA). RESULTS:Oral pretreatment during 4 days at 100 mg/kg increased liver regeneration index. At 200 mg/kg, AST level was statistically decreased in comparison to the group submited to distilled water administration. The other enzymes assessed disclosed no difference when all groups were compared. CONCLUSION: The present study shows that the aqueous extract of Hyptis pectinata leaves contains some biological active principles that stimulate liver regeneration at 100 mg/kg and cause slight hepatic protection at 200 mg/kg.

scholarly journals Immunohistochemical Study of the Ameliorative Effect of Vitamin E on Liver Regeneration after Different Periods of Partial Hepatectomy

2018 ◽  
Vol 11 (2) ◽  
pp. 661-669
Author(s):  
Mervat M. Halawani ◽  
Gamal S. Abdul Aziz ◽  
Hanan A. Amin ◽  
Hesham N. Mustafa ◽  
Amira A. Elhaggagy
Keyword(s):  
Vitamin E ◽  
Liver Regeneration ◽  
Partial Hepatectomy ◽  
Proliferating Cell Nuclear Antigen ◽  
Inhibitory Effect ◽  
Nuclear Antigen ◽  
Albino Rats ◽  
Ameliorative Effect ◽  
Proliferating Cell ◽  
Control Sham

The liver is almost unique in its capacity for regeneration after hepatectomy but the exact mechanisms are not yet fully clarified. Antioxidants have been shown to promote liver regeneration after major hepatectomy. The present study evaluated the ameliorative effect of vitamin E administration on the liver regeneration after different periods of partial hepatectomy (PH) in rats. Fifty-six adult male albino rats were divided into three groups: Control sham operated group; partially hepatectomized group which were divided into three subgroups sacrificed at 1day, 3 days and 7days after the operation respectively; Partially Hepatectomized group with vitamin E pretreatment before PH where the rats were given a daily oral dose of vitamin E until the time of sacrifice of the rats. Immunohistochemical detection of proliferating cell nuclear antigen (PCNA) and labeling index were demonstrated. After PH, the PCNA positive hepatocytes and the PCNA labeling indices were significantly high after the 1st day and then much decreased after the 3rd day, to be followed by a slight increase at the 7th day. Vitamin E pretreatment in PH rats resulted in a decrease in PCNA positive cells and its labeling indices in the 1st day with a gradual increase in the 3rd and 7th days. Vitamin E has an inhibitory effect in the first 24 hours on liver regeneration followed by stimulatory effect at the third and seventh days after PH. These data indicated that vitamin E pretreatment has an important role in regulation and enhancement of liver regeneration after PH.

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