We investigated the effects of the oral administration of Korean red ginseng (KRG) on morphologic change and function of liver in dogs. Fifteen adult mongrel dogs (n=15) were divided into three groups: a control group (40% hepatectomy, untreated), a 250 group (40% hepatectomy, 250 mg/kg of KRG, PO), and a 500 group (40% hepatectomy, 500 mg/kg of KRG, PO). The liver regeneration, histologic findings, CBC (WBC, RBC, PCV, and PLT), and liver function tests (AST, ALT, GGT, ALP, LDH, and T-bil) were examined during experiment. The liver regeneration rates were higher in treated groups than in the control group. But, there were no significant differences. All hematological values were within normal ranges except leukocyte counts for 3 days postoperatively. The levels of AST and ALT in the treated groups were significantly decreased compared to that in the control group (p<0.05). The numbers of degenerative cells and area of connective tissue were significantly decreased in the liver of the dog with KRG administration (p<0.01). On the basis of these results, we could conclude that KRG accelerate the liver regeneration and ameliorate the liver injury after hepatectomy in dogs.
Animals ; Blood/drug effects ; Dogs ; Female ; Hepatectomy/*veterinary ; Liver/*drug effects/*surgery ; Liver Regeneration/*drug effects ; Male ; *Panax ; Plant Extracts/*pharmacology ; Plant Roots/chemistry

Administering of 2-acetylaminofluorene (2-AAF) before a two-thirds partial hepatectomy (PHx) results in suppression of hepatocyte proliferation and stimulation of oval cell proliferation. The objectives of this study was to examine the oval cell behaviour and associated transforming growth factor-beta1 (TGF-beta1) protein expression by combining 2-AAF with selective hepatic damage caused by PHx. We also studied the temporal relationship between TGF-beta1 expression, and proliferation and apoptosis of oval cells. Oval cells emerged from the portal areas and became more numerous with time fanning out into the periportal and midzonal hepatic parenchyma. Both smooth muscle actin (SMA) and TGF-beta1 immunostain revealed that TGF-beta1-positive cells were SMA-positive hepatic stellate cells (HSCs). Coinciding with the proliferation of oval cells, an increase expression of TGF-beta1 produced by SMA-positive HSCs was observed, thereafter apoptosis of oval cells reached its peak. This result implicated that TGF-beta1 produced by HSCs is intimately associated with proliferation and apoptosis of oval cells, and plays a role in the cessation of oval cell activation and remodeling of liver parenchyma in 2-AAF induced liver regeneration.
2-Acetylaminofluorene ; Animal ; Apoptosis/physiology* ; Hepatectomy ; Immunohistochemistry ; In Situ Nick-End Labeling ; Liver/ultrastructure ; Liver/metabolism* ; Liver/cytology ; Liver Regeneration/physiology* ; Liver Regeneration/drug effects ; Male ; Rats ; Rats, Sprague-Dawley ; Transforming Growth Factor beta/metabolism*

OBJECTIVETo investigate the effects of augmenter of liver regeneration (ALR) on the proliferation of hepatocytes and hepatic tumor cells and the expression of ALR in herpatocellular carcinoma (HCC).

METHODSPrimary rat hepatocytes, QGY and HepG2 cells were cultured separately with ALR from different species. Cell proliferation was detected by their 3H-TdR uptake. The expression of ALR was examined in 9 normal hepatic tissues and 21 HCC cases using immunohistochemistry method.

RESULTSDifferent ALRs could stimulate the proliferation of HepG2 and QGY cells in a dose-dependent way in vitro, but all ALR had no influence in the proliferation of primary rat hepatocytes. The expression of ALR was absent in normal hepatic tissues, but present in all HCC hepatic tissues. However, the expression of ALR had no relationship with the differentiation and size of the carcinomas.

CONCLUSIONALR might play an important role in the occurrence and development of HCC.

Animals ; Carcinoma, Hepatocellular ; metabolism ; Hepatocytes ; metabolism ; Liver Neoplasms ; metabolism ; Liver Regeneration ; drug effects ; physiology ; Male ; Proteins ; genetics ; metabolism ; Rats ; Rats, Wistar

Animals ; Bone Marrow Cells ; cytology ; Cell Differentiation ; drug effects ; Ethanol ; adverse effects ; Hepatocytes ; cytology ; Liver Regeneration ; Mesenchymal Stromal Cells ; cytology ; Rats ; Rats, Sprague-Dawley

Drug-induced liver injury (DILI) is a significant threat to patient health and a major concern during drug development. Recently, multiple circulating microRNAs (miRNAs) have been reported to be potential biomarkers for DILI. To adapt and validate miRNAs for clinical use, we investigated the time-course changes in miR-122 expression levels in an acetaminophen-induced liver injury model in rats. In addition, miR-155 and miR-21 were evaluated as makers of inflammation and regeneration, respectively, to characterize liver status. Our results revealed that miR-122 is an early and sensitive biomarker of hepatocellular injury at a stage when alanine transaminase, aspartate transaminase, and total bilirubin were not detectable. However, no significant differences in the expression levels of other miRNAs (miR-155 and -21) were observed between treatment and vehicle groups. Collectively, these time-course changes in the expression levels of miRNAs may be useful as markers for clinical decision-making, in the diagnosis and treatment of DILI.
Acetaminophen/*toxicity ; Animals ; Biomarkers/*blood ; Chemical and Drug Induced Liver Injury/*blood/*diagnosis/pathology ; Gene Expression Profiling ; Gene Expression Regulation/*drug effects ; Hepatocytes/*drug effects ; Inflammation/blood/diagnosis ; Liver Regeneration ; MicroRNAs/*blood/genetics ; Predictive Value of Tests ; Rats ; Time

Methylation events play a critical role in various cellular processes including regulation of gene transcription and proliferation. We observed that methyltransferase activity underwent time-dependent changes in the cytosol of the rat hepatocytes upon partial hepatectomy. However, any change in the methylation of nuclear proteins is not clear during hepatocyte proliferation. The nuclear fraction possesses basal level of methyltransferase to catalyze methylation of several proteins ranging from 7 to 70 kD prior to any hepatecmony. The specific p16 (16 kD) band was transiently and heavily methylated post 1 day hepatectomy, and then became non- detectable, but not in the control liver. Methylation of p16 band was completely inhibited by exogenously added histones, particularly 2AS, 1, 2A and 2B subtypes. The methylated p16 protein remains stable in either acid or alkali- induced demethylation conditions, indicating that methylation is not likely to occur on isoaspartyl or C-terminal cysteinyl residues. Exogenous addition of non-hydrolyzable GTP caused a dose- dependent suppression of a p16 methylation suggesting that G-proteins might play a role as an endogenous methylation inhibitor in vivo. Taken together, we have identified the proliferation event associated-methylation of the nuclear p16 protein in the hepatocytes undergoing liver regeneration.
Alkalies/pharmacology ; Animals ; Cell Proliferation ; Guanosine 5'-O-(3-Thiotriphosphate)/pharmacology ; Hepatectomy ; Hepatocytes/drug effects/*metabolism ; Histones/pharmacology ; Liver Regeneration/drug effects/*physiology ; Methylation/drug effects ; Nuclear Proteins/*metabolism ; Rats ; Research Support, Non-U.S. Gov't ; Sodium Chloride/pharmacology

OBJECTIVETo observe the effect of D-galactosamine (D-GaIN) and lipopolysaccharide (LPS) on liver tissue regeneration and repair in mice following liver injury induced by partial hepatectomy.

METHODSA total of 40 male BALB/c mice were randomly assigned into 2 equal groups to receive intraperitoneal injections of D-GaIN (500 mg/kg) plus LPS (50 µg/kg, given 1 h later) or two doses of saline 24 h prior to 1/3 hepatectomy. The liver weight/body weight (LW/BW) ratio and liver regeneration rate were observed at different time points after partial hepatectomy. Liver cell injury was assessed using HE staining, hepatocyte proliferation evaluated with BrdU staining, and the oval cell proliferation observed with immunohistochemistry.

RESULTSIn mice receiving saline injection, the liver volume was nearly restored 9 days after partial hepatectomy, while in mice with D-GaIN and LPS injections, the liver failed to recover the normal volume even at 14 days, showing a significant difference in the liver regeneration rate between them [(22.6∓105.93)% vs (9.49∓32.55)%, P<0.001]. Significant degenerative changes of the hepatic cells were found in D-GaIN/LPS-treated group, while only mild inflammatory reaction was observed in saline-treated group after partial hepatectomy. Obvious hepatocyte proliferation was observed at day 7 in saline-treated group but not in D-GaIN/LPS-treated group. Oval cell proliferation in the portal area occurred 3 days after partial hepatectomy in D-GaIN/LPS-treated group.

CONCLUSIOND-GaIN and LPS can obviously inhibit hepatocyte regeneration after liver injury in mice. D-GaIN and LPS combined with partial hepatectomy can induce oval cell proliferation.

Animals ; Cell Proliferation ; drug effects ; Galactosamine ; pharmacology ; Hepatectomy ; methods ; Lipopolysaccharides ; pharmacology ; Liver ; cytology ; injuries ; physiopathology ; Liver Regeneration ; drug effects ; physiology ; Male ; Mice ; Mice, Inbred BALB C ; Stem Cells ; cytology

OBJECTIVETo assess the effect of Danshen on liver regeneration capacity of carbon tetrachloride-induced liver injury rats.

METHODComputer retrieval of data from CJFD, CBM, Chinese science & technology journal full-text database and Chinese medical association digital journals, and such foreign databases as PubMed, EMBASE and SCI was included in the randomized controlled trials (RCT) of rat liver injury induced by carbon tetrachloride,with the search as at May 2012. A Meta analysis was made using Rev-Man 5.1 software. Using the GRADE system to addess five outcomes in stuay.

RESULTTwo hundred and fourteen rats got involved in seven randomized trials. Meta analysis showed there were statistical differences between the Danshen group and the control group in alanine aminotransferase (ALT), aspartate aminotransferase (AST), superoxide dismutase (SOD), tumor necrosis factor-alpha (TNF-alpha) and hyaluronic acid (HA) after rat liver injury induced by carbon tetrachloride. When we used system to each outcome, because of serious limitations and indirect, they are all very low quality.

CONCLUSIONDanshen shows certain promoting effect to liver regeneration in carbon tetrachloride-induced liver injury rats.

Animals ; Carbon Tetrachloride ; adverse effects ; Chemical and Drug Induced Liver Injury ; etiology ; genetics ; metabolism ; physiopathology ; Disease Models, Animal ; Drugs, Chinese Herbal ; pharmacology ; Humans ; Liver Regeneration ; drug effects ; Phenanthrolines ; pharmacology ; Rats ; Salvia miltiorrhiza ; chemistry

BACKGROUNDConsidering the existence of a large number of liver cell degeneration and necrosis in fibrotic liver, liver function was damaged severely and could not effectively regenerate after partial hepatectomy (PHx). The aim of this study was to investigate whether decorin (DCN) could promote the liver regeneration after PHx in fibrotic mice.

METHODSForty mice (5-week-old, Balb/c) were injected with CCl4 intraperitoneally and liver fibrosis model was established after 5 weeks. The survival mice were randomly divided into two groups: control group and DCN group. Then, we performed 70% PHx on all these mice and injected DCN or phosphate-buffered saline plus normal saline (NS) to each group, respectively, after surgery. Liver body weight ratio (LBR), quantitative real-time polymerase chain reaction, and immunohistochemistry were used to analyze liver regeneration and fibrosis degree in both groups, and to find out whether exogenous protein DCN could promote the regeneration of fibrosis liver after PHx.

RESULTSExpressions of a-smooth muscle actin (SMA) mRNA and LBR had significant increases in the DCN group at postoperative Day 3 (POD 3, P < 0.05). The protein expressions of CD31, a-SMA, and tumor necrosis factor (TNF)-a were higher in the DCN group than those in the control group by immunohistochemistry at POD 3 (P < 0.05).

CONCLUSIONExogenous protein DCN could promote liver regeneration after PHx in fibrotic mice.

Animals ; Decorin ; therapeutic use ; Hepatectomy ; Immunohistochemistry ; Liver Cirrhosis ; drug therapy ; metabolism ; surgery ; Liver Regeneration ; drug effects ; Male ; Mice ; Mice, Inbred BALB C ; Platelet Endothelial Cell Adhesion Molecule-1 ; metabolism

OBJECTIVEThis study was conducted to determine the histopathological and biochemical effects of Thymus algeriensis essential oil (TEO) on hydrogen peroxide (H2O2)-induced oxidative stress in liver and kidney tissues of rats.

METHODSRats were treated in six groups and were exposed for 2 weeks to low (LD; 100 μmol/L) and high doses (HD; 1 mmol/L) of H2O2 in the presence or absence of TEO (180 mg/kg). Liver and kidney atrophy was measured by using biochemical and histopathological assays.

RESULTSOur study demonstrated that H2O2 induced liver and kidney atrophy, as evidenced by the significant elevation of serum aminotransferase, urea, and creatinine levels compared with those in the control rats. Urea levels were estimated by evaluating the activity of serum urease that hydrolyzes urea into CO2 and ammonia. However, TEO treatment significantly alleviated oxidative stress in the H2O2-induced liver and kidney toxicity model by reducing the levels of malondialdehyde concomitantly with marked elevations in superoxide dismutase, catalase, glutathione peroxidase, and glutathione S-transferase, as well as decrease in glutathione activity.

CONCLUSIONOur data demonstrated that TEO protected against H2O2 toxicity by decreasing oxidant levels and DNA damage, as well as increasing antioxidant levels, indicating that TEO has a spectrum of antioxidant and DNA-protective properties.

Animals ; Antioxidants ; pharmacology ; Hydrogen Peroxide ; metabolism ; toxicity ; Kidney ; drug effects ; physiology ; Lipid Metabolism ; drug effects ; Liver ; drug effects ; physiology ; Male ; Malondialdehyde ; metabolism ; Oils, Volatile ; pharmacology ; Oxidative Stress ; drug effects ; Plant Extracts ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Regeneration ; drug effects ; Thymus Plant ; chemistry