scholarly journals Silymarin Accelerates Liver Regeneration after Partial Hepatectomy

2015 ◽  
Vol 2015 ◽  
pp. 1-14 ◽  
Author(s):  
Jia-Ping Wu ◽  
Chin-Chuan Tsai ◽  
Yu-Lan Yeh ◽  
Yueh-Min Lin ◽  
Chien-Chung Lin ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Liver Regeneration ◽  
Partial Hepatectomy ◽  
Tissue Injury ◽  
Hepatic Regeneration ◽  
Sprague Dawley ◽  
Rt Pcr ◽  
Sprague Dawley Rats ◽  
M Phase ◽  
G2 Phase

Partial hepatectomy (PHx) is a liver regeneration physiological response induced to maintain homeostasis. Liver regeneration evolved presumably to protect wild animals from catastrophic liver loss caused by toxins or tissue injury. Silymarin (Sm) ability to stimulate liver regeneration has been an object of curiosity for many years. Silymarin has been investigated for use as an antioxidant and anticarcinogen. However, its use as a supportive treatment for liver damage is elusive. In this study, we fed silymarin (Sm, 25 mg/kg) to male Sprague-Dawley rats for 7 weeks. Surgical 2/3 PHx was then conducted on the rats at 6 hrs, 24 hrs, and 72 hrs. Western blot and RT-PCR were conducted to detect the cell cycle activities and silymarin effects on hepatic regeneration. The results showed that silymarin enhanced liver regeneration by accelerating the cell cycle in PHx liver. Silymarin led to increased G1 phase (cyclin D1/pRb), S phase (cyclin E/E2F), G2 phase (cyclin B), and M phase (cyclin A) protein and mRNA at 6 hrs, 24 hrs, and 72 hrs PHx. HGF, TGFα, and TGFβ1 growth factor expressions were also enhanced. We suggest that silymarin plays a crucial role in accelerated liver regeneration after PHx.

scholarly journals Corosolic Acid Inhibits Tumor Growth without Compromising ALPPS-induced Liver Regeneration in Rats

2020 ◽  
Author(s):  
Jinwei zhao ◽  
xueyue luo ◽  
weiyi zhao ◽  
hong zhou ◽  
hongyue xu ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Liver Regeneration ◽  
Macrophage Polarization ◽  
Hepatic Regeneration ◽  
M2 Macrophage ◽  
Portal Vein Ligation ◽  
Sprague Dawley ◽  
Regeneration Rate ◽  
Sprague Dawley Rats ◽  
Corosolic Acid

Abstract BackgroudThe associating liver partition and portal vein ligation (ALPPS) technique is a promising strategy for unresectable tumors without sufficient future liver remnants (FLRs). Criticism has focused on its stimulation of tumor growth. This study explores the effect of corosolic acid (CA) on inhibiting tumor growth without compromising ALPPS-induced liver regeneration and investigates its possible mechanism.MethodsThe ALPPS procedure was performed in Sprague-Dawley rats with orthotopic liver cancer. Blood, tumor and FLR samples in different group were collected.ResultsThe tumor weight in the implantation/ALPPS/CA group was lower than that in the implantation/ALPPS group (p < 0.05). On postoperative day 15, the hepatic regeneration rate and the expression of Ki67+ hepatocytes in the FLRs increased significantly in the group that underwent ALPPS. The number of CD86+ macrophages increased in the FLRs and tumors of the groups that underwent the ALPPS procedure. Additionally, the number of CD206+ macrophages was higher than the number of CD86+ macrophages in the tumors of the implantation group and the implantation/ALPPS group (p < 0.01, respectively); however, the opposite results were observed in the CA groups. The administration of CA downregulated the expression of TGF-β, CD31 and PD-1, whereas it increased the number of CD8+ lymphocytes in tumors.ConclusionsCA inhibits tumor growth without compromising ALPPS-induced liver regeneration. This result may be attributed to the CA-induced downregulation of PD-1 and TGF-β expression and the increased CD8+ lymphocyte infiltration in tumor tissue, associated with the suppression of M2 macrophage polarization.

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.

THE INFLUENCE OF TUMOR GROWTH ON THE SYNTHESIS OF α2-AP (ACUTE PHASE) GLOBULIN OF RAT SERUM

1967 ◽  
Vol 45 (12) ◽  
pp. 1937-1941 ◽  
Author(s):  
Henry E. Weimer ◽  
Constance Humelbaugh ◽  
Dorothy M. Roberts
Keyword(s):  
Tumor Growth ◽  
Acute Phase ◽  
Tissue Injury ◽  
Sprague Dawley ◽  
Rat Serum ◽  
Serum Haptoglobin ◽  
Sprague Dawley Rats ◽  
Walker 256 ◽  
Implantation Procedure

The effects of growth of the Walker 256 carcinosarcoma on the α2-AP (acute phase) globulin, fibrinogen, seromucoid, and haptoglobin fractions of plasma were investigated in adult, male Sprague–Dawley rats in a longitudinal study. Early increases in α2-AP globulin and seromucoid levels were found to be related to the tissue injury associated with the implantation procedure. Significant elevations in the α2-AP globulin, fibrinogen, and seromucoid fractions coincided with the onset of progressive tumor growth. Serum haptoglobin concentrations exhibited a delayed rise. This was attributed to the in vivo formation of haptoglobin–hemoglobin complexes. It was suggested that the increases in all fractions reflected the release of humoral mediators from injured or necrotic cells wrhich stimulated increased synthesis of the fractions by the liver.

scholarly journals Pregnancy facilitates maternal liver regeneration after partial hepatectomy

2020 ◽  
Vol 318 (4) ◽  
pp. G772-G780
Author(s):  
Joonyong Lee ◽  
Veronica Garcia ◽  
Shashank Manohar Nambiar ◽  
Huaizhou Jiang ◽  
Guoli Dai
Keyword(s):  
Cell Cycle ◽  
Growth Factor ◽  
Liver Resection ◽  
Liver Regeneration ◽  
Partial Hepatectomy ◽  
Liver Fat ◽  
Fat Accumulation ◽  
Positive Effects ◽  
Maternal Liver ◽  
Hepatic Fat

Liver resection induces robust liver regrowth or regeneration to compensate for the lost tissue mass. In a clinical setting, pregnant women may need liver resection without terminating pregnancy in some cases. However, how pregnancy affects maternal liver regeneration remains elusive. We performed 70% partial hepatectomy (PH) in nonpregnant mice and gestation day 14 mice, and histologically and molecularly compared their liver regrowth during the next 4 days. We found that compared with the nonpregnant state, pregnancy altered the molecular programs driving hepatocyte replication, indicated by enhanced activities of epidermal growth factor receptor and STAT5A, reduced activities of cMet and p70S6K, decreased production of IL-6, TNFα, and hepatocyte growth factor, suppressed cyclin D1 expression, increased cyclin A1 expression, and early activated cyclin A2 expression. As a result, pregnancy allowed the remnant hepatocytes to enter the cell cycle at least 12 h earlier, increased hepatic fat accumulation, and enhanced hepatocyte mitosis. Consequently, pregnancy ameliorated maternal liver regeneration following PH. In addition, a report showed that maternal liver regrowth after PH is driven mainly by hepatocyte hypertrophy rather than hyperplasia during the second half of gestation in young adult mice. In contrast, we demonstrate that maternal liver relies mainly on hepatocyte hyperplasia instead of hypertrophy to restore the lost mass after PH. Overall, we demonstrate that pregnancy facilitates maternal liver regeneration likely via triggering an early onset of hepatocyte replication, accumulating excessive liver fat, and promoting hepatocyte mitosis. The results from our current studies enable us to gain more insights into how maternal liver regeneration progresses during gestation. NEW & NOTEWORTHY We demonstrate that pregnancy may generate positive effects on maternal liver regeneration following partial hepatectomy, which are manifested by early entry of the cell cycle of remnant hepatocytes, increased hepatic fat accumulation, enhanced hepatocyte mitosis, and overall accelerated liver regrowth.

THE PRESENCE OF A MITOSIS INHIBITOR IN THE SERUM AND LIVER OF ADULT RATS

1958 ◽  
Vol 36 (8) ◽  
pp. 855-859 ◽  
Author(s):  
H. F. Stich ◽  
M. L. Florian
Keyword(s):  
Partial Hepatectomy ◽  
Specific Inhibitor ◽  
Mitotic Rate ◽  
Regenerating Liver ◽  
Sprague Dawley ◽  
Adult Rats ◽  
Sprague Dawley Rats ◽  
Organ Specific ◽  
Tissue Homogenates ◽  
Liver Homogenates

The influence of serum and tissue homogenates on the mitotic rate of regenerating liver was tested. The following fractions were injected into Sprague–Dawley rats 24 hours after partial hepatectomy: (a) serum from normal 290–340 g. rats; (b) serum from rats 24 or 72 hours following partial hepatectomy; (c) liver homogenates from normal 290–340 g. rats; (d) regenerating liver homogenates (24 hours after partial hepatectomy); and, as controls, (e) brain homogenates representing non-mitotic tissues; (f) testes homogenates representing mitotically active tissues. Serum and liver from adult animals inhibit the onset of mitosis. Serum and regenerating liver from partially hepatectomized rats, as well as heterologous tissue, show no retarding effect.The results suggest the presence of an organ-specific inhibitor of mitosis in the serum and liver of adult animals.

scholarly journals Cardioprotective Effect of Danhong Injection against Myocardial Infarction in Rats Is Critically Contributed by MicroRNAs

2019 ◽  
Vol 2019 ◽  
pp. 1-14 ◽  
Author(s):  
Jingrui Chen ◽  
Jing wei ◽  
John Orgah ◽  
Yan Zhu ◽  
Jingyu Ni ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Cardiac Function ◽  
Ventricular Remodeling ◽  
Nuclear Translocation ◽  
Inflammatory Factors ◽  
Sprague Dawley ◽  
Rt Pcr ◽  
Danhong Injection ◽  
Sprague Dawley Rats ◽  
Masson Staining

Background. Danhong injection (DHI) has been mainly used for the treatment of myocardial infarction, atherosclerosis, and coronary heart disease in clinical practice. Our previous studies have shown that DHI improves ventricular remodeling and preserves cardiac function in rats with myocardial infarction (MI). In this study, we focused on the potential mechanism of DHI in protecting cardiac function in MI rats. Methods. Sprague-Dawley rats were subjected to ligation of the left anterior descending coronary artery (LAD) to prepare a myocardial infarction (MI) model. After 14 day DHI intervention, cardiac function was measured by echocardiography and myocardial fibrosis was assessed by Masson staining. Differentiated miRNAs were screened using rat immunopathology miScript miRNA PCR arrays, and their results were verified by RT-PCR, immunofluorescence, and immunoblotting. Results. DHI treatment significantly reduced infarct size and improved cardiac function and hemodynamics in MI rats by echocardiography and morphology. miRNA PCR array results showed that DHI reversed 25 miRNAs known to be associated with inflammation and apoptosis. Moreover, the expression of inflammatory factors TNF-α, IL-1β, and IL-6 was significantly reduced in the treated DHI group. Mechanistically, DHI downregulated the inflammatory transcription factor NF-κB (as reflected by inhibition of NF-κB p65 nuclear translocation and phosphorylation of the IκBα). Conclusions. DHI is effective in mitigating inflammation associated with MI by preventing NF-κB nuclear translocation and regulating miRNAs, thereby improving cardiac function in myocardial infarction rats.

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 A novel form of Deleted in breast cancer 1 (DBC1) lacking the N-terminal domain does not bind SIRT1 and is dynamically regulated in vivo

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Leonardo Santos ◽  
Laura Colman ◽  
Paola Contreras ◽  
Claudia C. Chini ◽  
Adriana Carlomagno ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Liver Regeneration ◽  
Partial Hepatectomy ◽  
Normal Cell ◽  
Cell Cycle Progression ◽  
Cycle Progression ◽  
Quiescent Cells ◽  
Normal Cell Cycle

Abstract The protein Deleted in Breast Cancer-1 is a regulator of several transcription factors and epigenetic regulators, including HDAC3, Rev-erb-alpha, PARP1 and SIRT1. It is well known that DBC1 regulates its targets, including SIRT1, by protein-protein interaction. However, little is known about how DBC1 biological activity is regulated. In this work, we show that in quiescent cells DBC1 is proteolytically cleaved, producing a protein (DN-DBC1) that misses the S1-like domain and no longer binds to SIRT1. DN-DBC1 is also found in vivo in mouse and human tissues. Interestingly, DN-DBC1 is cleared once quiescent cells re-enter to the cell cycle. Using a model of liver regeneration after partial hepatectomy, we found that DN-DBC1 is down-regulated in vivo during regeneration. In fact, WT mice show a decrease in SIRT1 activity during liver regeneration, coincidentally with DN-DBC1 downregulation and the appearance of full length DBC1. This effect on SIRT1 activity was not observed in DBC1 KO mice. Finally, we found that DBC1 KO mice have altered cell cycle progression and liver regeneration after partial hepatectomy, suggesting that DBC1/DN-DBC1 transitions play a role in normal cell cycle progression in vivo after cells leave quiescence. We propose that quiescent cells express DN-DBC1, which either replaces or coexist with the full-length protein, and that restoring of DBC1 is required for normal cell cycle progression in vitro and in vivo. Our results describe for the first time in vivo a naturally occurring form of DBC1, which does not bind SIRT1 and is dynamically regulated, thus contributing to redefine the knowledge about its function.

scholarly journals Fluctuation in radioresponse of HeLa cells during the cell cycle evaluated based on micronucleus frequency

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Hiroaki Shimono ◽  
Atsushi Kaida ◽  
Hisao Homma ◽  
Hitomi Nojima ◽  
Yusuke Onozato ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Hela Cells ◽  
Time Lapse ◽  
S Phase ◽  
G1 Phase ◽  
M Phase ◽  
G2 Phase ◽  
The Difference ◽  
Time Lapse Imaging ◽  
First Time

AbstractIn this study, we examined the fluctuation in radioresponse of HeLa cells during the cell cycle. For this purpose, we used HeLa cells expressing two types of fluorescent ubiquitination-based cell cycle indicators (Fucci), HeLa-Fucci (CA)2 and HeLa-Fucci (SA), and combined this approach with the micronucleus (MN) assay to assess radioresponse. The Fucci system distinguishes cell cycle phases based on the colour of fluorescence and cell morphology under live conditions. Time-lapse imaging allowed us to further identify sub-positions within the G1 and S phases at the time of irradiation by two independent means, and to quantitate the number of MNs by following each cell through M phase until the next G1 phase. Notably, we found that radioresponse was low in late G1 phase, but rapidly increased in early S phase. It then decreased until late S phase and increased in G2 phase. For the first time, we demonstrated the unique fluctuation of radioresponse by the MN assay during the cell cycle in HeLa cells. We discuss the difference between previous clonogenic experiments using M phase-synchronised cell populations and ours, as well as the clinical implications of the present findings.

scholarly journals TLC388 Induces DNA Damage and G2 Phase Cell Cycle Arrest in Human Non-Small Cell Lung Cancer Cells

2020 ◽  
Vol 27 (1) ◽  
pp. 107327481989797
Author(s):  
Kun-Ming Wu ◽  
Chih-Wen Chi ◽  
Jerry Cheng-Yen Lai ◽  
Yu-Jen Chen ◽  
Yu Ru Kou
Keyword(s):  
Lung Cancer ◽  
Cell Cycle ◽  
Cyclin B1 ◽  
Small Cell ◽  
Phase Cell ◽  
Small Cell Lung ◽  
Cycle Arrest ◽  
M Phase ◽  
G2 Phase ◽  
Induced Apoptosis

TLC388, a camptothecin-derivative targeting topoisomerase I, is a potential anticancer drug. In this study, its effect on A549 and H838 human non-small cell lung cancer (NSCLC) cells was investigated. Cell viability and proliferation were determined by thiazolyl blue tetrazolium bromide and clonogenic assays, respectively, and cell cycle analysis and detection of phosphorylated histone H3 (Ser10) were performed by flow cytometry. γ-H2AX protein; G2/M phase-associated molecules ataxia-telangiectasia mutated (ATM), CHK1, CHK2, CDC25C, CDC2, and cyclin B1; and apoptosis were assessed with immunofluorescence staining, immunoblotting, and an annexin V assay, respectively. The effect of co-treatment with CHIR124 (a checkpoint kinase 1 [CHK1] inhibitor) was also studied. TLC388 decreased the viability and proliferation of cells of both NSCLC lines in a dose-dependent manner. TLC388 inhibited the viability of NSCLC cell lines with an estimated concentration of 50% inhibition (IC50), which was 4.4 and 4.1 μM for A549 and H838 cells, respectively, after 24 hours. Moreover, it resulted in the accumulation of cells at the G2/M phase and increased γ-H2AX levels in A549 cells. Levels of the G2 phase–related molecules phosphorylated ATM, CHK1, CHK2, CDC25C, and cyclin B1 were increased in TLC388-treated cells. CHIR124 enhanced the cytotoxicity of TLC388 toward A549 and H838 cells and induced apoptosis of the former. TLC388 inhibits NSCLC cell growth by inflicting DNA damage and activating G2/M checkpoint proteins that trigger G2 phase cell cycle arrest to enable DNA repair. CHIR124 enhanced the cytotoxic effect of TLC388 and induced apoptosis.

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