Injection Of D-galactosamine Research Articles

Protective effects of antioxidant combination against D‐galactosamine‐induced kidney injury in rats

The protective effects of an antioxidant combination in kidney injury induced by the injection of D-galactosamine (D-GaIN) were examined in the present study. Sprague Dawley female rats were used and divided into four groups as follows: (1) animals injected physiological saline solution, intraperitoneally, (2) animals treated with the combination of ascorbic acid (100 mg kg(-1) day(-1)), beta-carotene (15 mg kg(-1) day(-1)), alpha-tocopherol (100 mg kg(-1) day(-1)), and sodium selenate (0.2 mg kg(-1) day(-1)) for three days orally, (3) rats injected D-GaIN (500 mg kg(-1)) intraperitoneally as a single dose, and (4) animals treated with the antioxidant combination for three days, then injected D-GaIN. The tissue and blood samples of animals were collected for morphological and biochemical evaluations. Histopathological injury in kidney tissues was observed together with a significant increase in tissue lipid peroxidation (LPO) level, myeloperoxidase (MPO), lactate dehydrogenase, catalase and superoxide dismutase (SOD) activities, and serum creatinine and urea levels, and a significant decrease in glutathione level and glutathione peroxidase activity in D-GaIN injected rats. However, a decrease in the degenerative changes was detected in the kidney tissue of D-GaIN + antioxidant group, and biochemical results showed reversed effects. In conclusion, it seems reasonable to conclude that the treatment of the antioxidant combination has a protective effect on D-GaIN-induced kidney injury of rats.

Effects of Gut Microflora on Hepatic Damage After Acute Liver Injury in Rats

Liver injury often causes disruption of the gut microflora. The aim of this work was to evaluate the effects of microflora variations on acute liver injury. Sprague-Dawley rats received saline, probiotics, Escherichia coli, Salmonella enteritidis, or gentamicin via daily gavage for 7 days. Acute liver injury was induced on the eighth day by intraperitoneal injection of d-galactosamine except for the normal group. Samples were collected 24 hours later. Bacterial translocation (BT) was evaluated from the liver, spleen, kidney, and mesenteric lymph nodes. Liver enzymes, histologic analysis, endotoxin, serum tumor necrosis factor-alpha, interleukin (IL)-6, IL-10, IL-12, CD3 and CD4 T cells in peripheral blood and Peyer's patches, intestinal bacteria, and intestinal mucosal ultrastructure were studied. Orally administered probiotics, nonpathogenic E. coli, and gentamicin, respectively, markedly attenuated liver damage, decreased BT, and decreased the levels of serum tumor necrosis factor-alpha, IL-6, IL-10, and IL-12. Treatment with S. enteritidis had opposite results. Only orally supplemented S. enteritidis significantly affected the CD3 and CD4 T cells counts in peripheral blood and Peyer's patches. We demonstrated that modifications in gut microflora had different effects on the prevention or exacerbation of acute liver injury. Moreover, alterations in gut microflora affected liver damage through three major factors: BT and the release of local gut cytokine and endotoxin.

Recombinant polypeptide of N-terminal heparin-binding domain of fibronectin antagonizes hepatic failure induced by endotoxin in mice

To study the preventive effect of recombinant polypeptide of N-terminal heparin-binding domain of fibronectin on hepatic failure induced by endotoxin in mice. The 40 hepatic failure Balb/C mice were established by intraperitoneal injection of lipopolysaccharide (LPS) and d-galactosamine (GalN). The mice were randomly divided into two groups, one for polypeptide treatment, the othe for saline treatment.Another 20 mice were used as normal control. Half hour prior to, 1, 2, and 3 hours after injection of LPS and GalN, the rhFNHN-29 polypeptide (10 mg/kg) was injected through the tail vein of mice. The same volume of saline was given to the saline treated group and the normal control group.Six hours after the injection of LPS and GalN, 250 microl blood was taken from the eye vein of each mouse for plasma TNFalpha testing, and 72 hours after the injection, mortality rates of the mice of different groups were observated. The liver, lung, heart, kidney, and brain tissues of the survival mice were examined for histopathology after 72 hours. The Liver tissue was also examined for electron micrograph and for mRNA expression of TNFalpha, IL-1beta, IL-6 by RT-PCR. The 72 hours mortality rates in saline-treated and polypeptide treated-mice were 70% and 15% respectively (P < 0.01). The histopathology showed that necrosis occurred less on the hepatocytes of polypeptide treated mice than on the saline treated ones. The ultrastructure of hepatocyte under the electron microscope showed that cell apparatus of saline treated mice were destroyed and cytoplasm become loose. The expression level of TNFalpha, IL-1beta, IL-6 mRNA on hepatocytes in polypeptide treated mice was significantly lower (1.26 +/- 0.37, 0.98 +/- 0.21, 0.43 +/- 0.17, 87.43 +/- 16.7 respectively) than that in the saline treated ones (1.98 +/- 0.56, 1.24 +/- 0.35, 0.64 +/- 0.25 and 236.11 +/- 32.7, respectively) (P < 0.01). Similarly, the plasm TNFalpha level (87.43 +/- 16.7) in polypeptide treated group was significantly lower than that (236.11 +/- 32.7) in the saline treated group (P < 0.01). The rhFNHN-29 polypeptide can prevent and treat hepatic failure induced by endotoxin. The mechanism by which the polypeptide takes the effect may involve its ability to down-regulate expression of those inflammation factors such as TNFalpha, IL-1beta, IL-6.

IL-2 Regulates SEB Induced Toxic Shock Syndrome in BALB/c Mice

BackgroundToxic Shock Syndrome (TSS) is characterized by fever, rash, hypotension, constitutional symptoms, and multi-organ involvement and is caused by Staphylococcus aureus enterotoxins such as Staphylococcal Enterotoxin B (SEB). SEB binds to the MHC-IIα chain and is recognized by the TCRβ chain of the Vβ8 TCR+ T cells. The binding of SEB to Vβ chain results in rapid activation of T cells and production of inflammatory cytokines, such as Interleukin-2 (IL-2), Interferon-γ and Tumor Necrosis Factor-α which mediate TSS. Although IL2 was originally identified as the T cell growth factor and was proposed to contribute to T cell differentiation, its role in TSS remains unexplored.Methodology/Principal FindingsMice were injected with D-Gal (25 mg/mouse). One hour after D-Galactosamine (D-Gal) injection each mouse was injected with SEB (20 µg/mouse. Mice were then observed for 72 hrs and death was recorded at different times. We tested Interleukin-12, IFNγ, and IL-2 deficient mice (IL-2−/−), but only the IL-2 deficient mice were resistant to SEB induced toxic shock syndrome. More importantly reconstitution of IL-2 in IL-2 deficient mice restored the shock. Interestingly, SEB induced IL-2 production from T cells was dependent on p38MAPK activation in macrophages as inhibition of it in macrophages significantly inhibited IL-2 production from T cells.ConclusionThis study shows the importance of IL -2 in TSS which has not been previously explored and it also shows that regulating macrophages function can regulate T cells and TSS.

ONO 3403, a synthetic serine protease inhibitor, inhibits lipopolysaccharide-induced tumor necrosis factor-α and nitric oxide production and protects mice from lethal endotoxic shock

ONO 3403, a new synthetic serine protease inhibitor, is a derivative of camostat mesilate and has a higher protease-inhibitory activity. The effect of ONO 3403 on lipopolysaccharide (LPS)-induced tumor necrosis factor (TNF)-α and nitric oxide (NO) production in RAW 264.7 macrophage-like cells was examined. ONO 3403 significantly inhibited LPS-induced TNF-α production at a lower concentration than camostat mesilate. It also inhibited LPS-induced NO production. Their inhibition was responsible for the reduced mRNA expression of TNF-α and inducible NO synthase. In LPS-stimulated cells, ONO 3403 prevented the augmentation of MyD88 expression and inhibited the phosphorylation of IκB-α, stress-activated protein kinase (SAPK) and IRF-3, and the production of interferon-β. ONO 3403 abolished the elevation of the extracellular serine protease activity in response to LPS. Further, it reduced the circulating TNF-α level, hepatic injury and mortality in mice receiving an injection of D-galactosamine and LPS. ONO 3403 was suggested to inhibit LPS-induced inflammatory responses via inactivation of MyD88-dependent and independent pathways.

Impaired Hepatocyte Regeneration in Acute Severe Hepatic Injury Enhances Effective Repopulation by Transplanted Hepatocytes

Efficient repopulation by transplanted hepatocytes in the severely injured liver is essential for their clinical application in the treatment of acute hepatic failure. We studied here whether and how the transplanted hepatocytes are able to efficiently repopulate the toxin-induced acute injured liver. Male dipeptidyl peptidase IV-deficient F344 rats were randomized to receive retrorsine plus D-galactosamine (R+D-gal) treatment or D-galactosamine-alone (D-gal) to induce acute hepatic injury, and retrorsine-alone. In these models, retrorsine was used to inhibit the proliferation of endogenous hepatocytes while D-galactosamine induced acute hepatocyte damage. Wild-type hepatocytes (1 x 10(7)/ml) were transplanted intraportally 24 h after D-galactosamine or saline injection. The kinetics of proliferation and repopulation of transplanted cells and the kinetics of cytokine response, hepatic stellate cell (HSC) activation, and matrix metalloproteinase (MMP2) expression were analyzed. We observed that early entry of transplanted hepatocytes into the hepatic plates and massive repopulation of the liver by transplanted hepatocytes occurred in acute hepatic injury induced by R+D-gal treatment but not by D-gal-alone or retrorsine-alone. The expressions of transforming growth factor-alpha and hepatocyte growth factor genes in the R+D-gal injured liver were significantly upregulated and prolonged up to 4 weeks after hepatocyte transplantation. The expression kinetics were parallel with the efficient proliferation and repopulation of transplanted hepatocytes. HSC was activated rapidly, markedly, and prolongedly up to 4 weeks after hepatocyte transplantation, when the expression of HGF gene and repopulation of transplanted hepatocytes were reduced afterward. Furthermore, the expression kinetics of MMP2 and its specific distribution in the host areas surrounding the expanding clusters of transplanted hepatocytes are consistent with those of activated HSC. Impaired hepatocyte regeneration after acute severe hepatic injury may initiate serial compensatory repair mechanisms that facilitate the extensive repopulation by transplanted hepatocytes that enter early the hepatic plates.

Hepatoprotective effects of salidroside on fulminant hepatic failure induced by d-galactosamine and lipopolysaccharide in mice

Abstract Objectives The aim was to investigate the protective effect of salidroside isolated from Rhodiola sachalinensis A. Bor. (Crassulaceae) on d-galactosamine/lipopolysaccharide-induced fulminant hepatic failure. Methods Hepatotoxicity was induced by an intraperitoneal injection of d-galactosamine (700 mg/kg) and lipopolysaccharide (10 μg/kg); salidroside (20, 50 and 100 mg/kg) was administered intraperitoneally 1 h before induction of hepatoxicity. Liver injury was assessed biochemically and histologically. Key findings Salidroside attenuated the induced acute increase in serum aspartate aminotransferase and alanine aminotransferase activities, and levels of tumour necrosis factor-alpha levels and serum nitric oxide. It restored depleted hepatic glutathione, superoxide dismutase, catalase and glutathione peroxidase activities, decreased malondialdehyde levels and considerably reduced histopathological changes. Histopathological, immunohistochemical and Western blot analyses also demonstrated that salidroside could reduce the appearance of necrotic regions and expression of caspase-3 and hypoxia-inducible factor-1α in liver tissue. Conclusions Salidroside protected liver tissue from the oxidative stress elicited by d-galactosamine and lipopolysaccharide. The hepatoprotective mechanism of salidroside appear to be related to antioxidant activity and inhibition of hypoxia-inducible factor-1α.

Hepatoprotective effects of salidroside on fulminant hepatic failure induced by D-galactosamine and lipopolysaccharide in mice

The aim was to investigate the protective effect of salidroside isolated from Rhodiola sachalinensis A. Bor. (Crassulaceae) on D-galactosamine/lipopolysaccharide-induced fulminant hepatic failure. Hepatotoxicity was induced by an intraperitoneal injection of D-galactosamine (700 mg/kg) and lipopolysaccharide (10 mug/kg); salidroside (20, 50 and 100 mg/kg) was administered intraperitoneally 1 h before induction of hepatoxicity. Liver injury was assessed biochemically and histologically. Salidroside attenuated the induced acute increase in serum aspartate aminotransferase and alanine aminotransferase activities, and levels of tumour necrosis factor-alpha levels and serum nitric oxide. It restored depleted hepatic glutathione, superoxide dismutase, catalase and glutathione peroxidase activities, decreased malondialdehyde levels and considerably reduced histopathological changes. Histopathological, immunohistochemical and Western blot analyses also demonstrated that salidroside could reduce the appearance of necrotic regions and expression of caspase-3 and hypoxia-inducible factor-1alpha in liver tissue. Salidroside protected liver tissue from the oxidative stress elicited by D-galactosamine and lipopolysaccharide. The hepatoprotective mechanism of salidroside appear to be related to antioxidant activity and inhibition of hypoxia-inducible factor-1alpha.

Enzyme-Linked Signaling

Activation of biliverdin reductase activates anti-inflammatory signaling through phosphatidylinositol 3-kinase and Akt.

Yogurt: Effect on Leukocytes and Blood Coagulation in an Acute Liver Injury Model

This study determined whether cow or goat yogurt administration has a preventive effect on the hepatic damage undergone during an acute liver injury. Acute liver injury was induced by an intraperitoneal injection of d-galactosamine. Groups of mice were fed with cow or goat yogurt for 2 days or 7 days before the d-galactosamine injection. Blood and liver samples were obtained 12 hours after d-galactosamine inoculation. d-Galactosamine induced an increase in serum amino-transaminases, a reduction in the number of blood leukocytes, an enhancement in neutrophil myeloperoxidase activity, a recruitment of leukocytes toward the liver, an increase in cell death, and an alteration in prothrombin time, activated partial thromboplastin time, and fibrinogen levels. Treatment with cow or goat yogurt was effective at increasing leukocyte number and decrease myeloperoxidase activity. We also observed a decrease in leukocyte accumulation in the liver and a reduction in cell death. Activated partial thromboplastin time and fibrinogen were normalized, but prothrombin time only showed an improvement without reaching normal values. Cow or goat yogurts were effective at protecting against an experimental acute liver injury, especially when administered for 7 days.

Lactobacillus casei: influence on the innate immune response and haemostatic alterations in a liver-injury model

Lactobacilllus casei CRL 431 has the ability to modulate the local and systemic immune responses, which are significantly involved in liver injury caused by hepatotoxins. This work was conducted to determine whether L. casei has a preventive effect on the hepatic damage undergone during an acute liver injury (ALI). ALI was induced by an intraperitoneal injection of d-galactosamine (D-Gal). Different groups of mice received 1x 109 L. casei cells/day/mouse for 2 days before D-Gal injection. Blood and liver samples were obtained 0, 6, 12, and 24 h after D-Gal administration. D-Gal induced increases in serum aminotransferases, reduced the number of blood leukocytes, enhanced neutrophil myeloperoxidase activity, increased dead cells, and altered prothrombin time and plasma fibrinogen levels. The preventive treatment with L. casei for 2 days modulated the innate immune response. This effect was shown by the earlier normalization of white blood cell counts, myeloperoxidase activity and aminotransferases levels. However, the haemostatic parameters were only partially recovered. The favourable effects obtained could be due to the capacity of L. casei to moderate the inflammatory response at the site of the injury with less damage to liver tissue.

Effects of Niupo Zhibao Pellet on high-mobility group box-1 protein expression in lung tissues of endotoxin shock rats

To observe the effects of Niupo Zhibao Pellet, a compound traditional Chinese herbal medicine, on high-mobility group box-1 protein (HMGB1) expression in lung tissues of rats with endotoxin shock. Thirty SPF Sprague-Dawley rats were randomly divided into control group, lipopolysaccharide (LPS) group and Niupo Zhibao Pellet group. Rats in Niupo Zhibao Pellet group were consecutively administered 7 days with 3 mL (1 g/L) Niupo Zhibao Pellet saline suspension every day by intragastric administration. Endotoxin shock was induced in rats of the LPS and Niupo Zhibao Pellet groups by intravenous injection of LPS (1.5 mg/kg) and intraperitoneal injection of D-galactosamine (100 mg/kg). Expression of HMGB1 in lung tissues was measured by immunohistochemical method with diaminobenzidine (DAB) coloration, fluorescein isothiocyanate (FITC) labeling, and by Western blotting. Expression of HMGB1 in lung tissues in the LPS group was increased and that in Niupo Zhibao Pellet group was higher than that in the LPS group and the control group. HMGB1 was presented in the cytoplasm of positive cells in the LPS group, but in the nucleus of positive cells in the Niupo Zhibao Pellet group. However, HMGB1 was little expressed in the lung tissues of normal rats. Niupo Zhibao Pellet can increase HMGB1 expression and locate HMGB1 in the nucleus but not the cytoplasm, which may be one of its mechanisms in reducing endotoxin shock.

Suppression of hepatic fat accumulation by highly purified eicosapentaenoic acid prevents the progression of d-galactosamine-induced hepatitis in mice fed with a high-fat/high-sucrose diet

The pathogenesis of non-alcoholic fatty liver disease (NAFLD) remains largely unknown. Here, we assessed the importance of hepatic fat accumulation on the progression of hepatitis. BALB/cA mice were fed with a standard diet (STD) or a high-fat and high-sucrose diet (HFHSD) for 14 days followed by intraperitoneal injection of d-galactosamine (DGalN) or vehicle. After 20–21 h, plasma and liver tissue were collected and analyzed. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels in plasma were increased significantly in HFHSD-fed mice treated with DGalN compared to STD-fed mice treated with DGalN. This exacerbation by the HFHSD was also observed in the plasma soluble tumor necrosis factor receptor (sTNFR) levels, and hepatic levels of reactive oxygen species (ROS) and the fibrogenic gene expression, such as tissue inhibitor of matrix metalloproteinase 1 (TIMP-1), connective tissue growth factor (CTGF) and osteopontin (OPN) in HFHSD-fed mice treated with DGalN. The triglyceride contents of the liver were significantly increased by the HFHSD. When eicosapentaenoic acid (EPA), a suppressor of sterol regulatory element binding protein 1 (SREBP-1), was administered to HFHSD-fed mice, the sensitivity of DGalN, as a result of plasma ALT and AST levels, was suppressed accompanied by reduced plasma sTNFR2 level and hepatic levels of triglyceride, ROS, and fibrogenic parameters, and by increased plasma adiponectin levels. These data suggest that the progression of steatotic liver injury closely depends on the accumulation of fat in the liver and is prevented by EPA through the suppression of the fatty liver change.

Protective effect of daidzin against d‐galactosamine and lipopolysaccharide‐induced hepatic failure in mice

This study examined the effects of daidzin, a major isoflavone from Puerariae Radix, on D-galactosamine (D-GalN) and lipopolysaccharide (LPS)-induced liver failure. Mice were given an intraperitoneal injection of daidzin (25, 50, 100 and 200 mg/kg) 1 h before receiving an injection of D-GalN (700 mg/kg)/LPS (10 microg/kg). Daidzin markedly reduced the elevated serum aminotransferase activity and the levels of lipid peroxidation and tumor necrosis factor-alpha. The glutathione content was lower in the D-GalN/LPS group, which was attenuated by daidzin. The daidzin pretreatment attenuated the swollen mitochondria observed in the d-GalN/LPS group. Daidzin attenuated the apoptosis of hepatocytes, which was confirmed using the terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling method and a caspase-3 assay. Overall, these results suggest that the liver protection of daidzin is due to reduced oxidative stress and its antiapoptotic activity.

Aqueous garlic extract attenuates hepatitis and oxidative stress induced by galactosamine/lipoploysaccharide in rats

Injection of D-galactosamine and lipopolysaccharide (DGaIN/LPS) is useful as an experimental model of acute hepatic damage. Juvenile rats were used for investigation. The hepatoprotective activity of aqueous garlic (Allium sativum) extract (AGE) at a dose of 300 mg/kg body weight for 14 days, intraperitoneal (i.p.) prior to the induction of DGalN/LPS, was investigated against DGalN/LPS-induced hepatitis in rats. DGalN/LPS (300 mg/kg body weight/30 microg/kg body weight, i.p.), induced hepatic damage that was manifested by a significant increase in the activities of marker enzymes [alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), lactate dehydrogenase (LDH) and gamma glutamyl transferase (gamma GT)], bilirubin, lipid peroxides (LPO), tumor necrosis factor (TNF-alpha) and myeloperoxidase (MPO) activity level in serum. Also, the lipid profile in serum and liver homogenate including total cholesterol, triglycerides, free fatty acids and phospholipids were significantly deteriorated. The antioxidant enzyme activities (superoxide dismutase, SOD; reduced glutathione, GSH; catalase, CAT and glutathione peroxidase, GPX) in liver homogenate were significantly decreased in the DGalN/LPS. Pretreatment of rats with AGE reversed these altered parameters near to normal control values. Results of this study revealed that AGE could afford a significant protection in the alleviation of DGalN/LPS-induced hepatic damage.

Influence of Piper betle on hepatic marker enzymes and tissue antioxidant status in D-galactosamine-induced hepatotoxic rats

D-galactosamine is a well-established hepatotoxicant that induces a diffuse type of liver injury closely resembling human viral hepatitis. D-galactosamine by its property of generating free radicals causes severe damage to the membrane and affects almost all organs of the human body. The leaves of Piper betle L., a commonly used masticatory in Asian countries, possess several biological properties. Our aim is to investigate the in vivo antioxidant potential of P. betle leaf-extract against oxidative stress induced by D-galactosamine intoxication in male albino Wistar rats. Toxicity was induced by an intraperitoneal injection of D-galactosamine, 400 mg/kg body weight (BW) for 21 days. Rats were treated with P. betle extract (200 mg/kg BW) via intragastric intubations. We assessed the activities of liver marker enzymes (aspartate amino-transferase, alanine aminotransferase, alkaline phosphatase, gamma glutamyl transpeptidase) and levels of thiobarbituric acid reactive substances (TBARS), lipid hydroperoxides, superoxide dismutase, catalase, glutathione peroxidase, vitamin C, vitamin E, and reduced glutathione. The extract significantly improved the status of antioxidants and decreased TBARS, hydroperoxides, and liver marker enzymes when compared with the D-galactosamine treated group, demonstrating its hepatoprotective and antioxidant properties.

Effects of granulocyte colony-stimulating factor on hepatocyte apoptosis in acute liver failure: experiment with rats

To explore the effects of granulocyte colony- stimulating factor (G-CSF) on hepatocyte apoptosis in acute liver failure (ALF) and possible mechanism thereof. One hundred and sixty SD rats underwent intraperitoneal injection of D-galactosamine (D-GalN) 1.4 g/kg so as to establish AFL models and then were randomly divided into 2 equal groups: G-CSF therapy group, injected hypodermically with recombinant human G-CSF 50 microg x kg(-1) x d(-1) 2 hours after D-GalN injection for 3 consecutive days, and placebo control group, injected hypodermically with normal saline for 3 consecutive days. Liver samples were collected from 6 rats of each group 6 h, 12 h, 1 day, and 3 days after D-GalN injection respectively. Another six normal rats were used as normal control group. Hepatocyte apoptosis rate was measured by flow cytometry. Immunohistochemistry was used to detect the expression of Bcl-2 and caspase-3, a proapoptosis protein, in the liver sections. The survival rate of the G-CSF therapy group was 53.3%, significantly higher than that of the placebo control group (33.3%, P = 0.027). The hepatocyte apoptosis rate and expression rates of Bcl-2 and caspase-3 in the liver sections after D-GalN injection increased along with time. The hepatocyte apoptosis rate peaked 1 day after the D-GalN injection in both groups. The maximum hepatocyte apoptosis rate of the G-CSF group was 29% +/- 7%, significantly lower than that of the placebo control group (44% +/- 12%, P = 0.026). The gray scale of Bcl-2 in liver sections at hour 12 of the G-CSF group was 152 +/- 37, significantly lower than that of the placebo control group (161 +/- 7, P = 0.012). and the gray scale of Bcl-2 on day 1 of the G-CSF group was 150 +/- 12, significantly lower than that of the placebo control group (159 +/- 9, P = 0.018). The gray scales of caspase-3 on days 1 and 3 of the G-CSF group were 189.6 +/- 4.6 and 184.7 +/- 4.8 respectively, both significantly higher than those of the placebo control group (169.6 +/- 15.7 and 160.0 +/- 5.0, both P = 0.000). Apoptosis is a key mechanism contributing to ALF. G-CSF prevents ALF induced by D-GalN, thus raising the survival rate. G-GSF shows an inhibitory efficacy on hepatocytes apoptosis by probably up-regulating Bcl-2 and reducing caspase-3 expression.

A Diterpenoid Acanthoic Acid from Acanthopanax koreanum Protects against D-Galactosamine/Lipopolysaccharide-Induced Fulminant Hepatic Failure in Mice

The hepatoprotective effects of a diterpenoid acanthoic acid isolated from Acanthopanax koreanum NAKAI were evaluated in a D-galactosamine/lipopolysaccharide-induced fulminant hepatic failure mouse model. Mice were pretreated orally with acanthoic acid 12 and 1 h before intraperitoneal injection of D-galactosamine and lipopolysaccharide. Pretreatment with the compound markedly reduced lethal liver injury in experimental animals. The effects were likely associated with a significant decrease in serum tumor necrosis factor (TNF)-alpha levels, which are correlated not only with those of alanine aminotransferase and aspartate aminotransferase but also with the reduced number of apoptotic hepatocytes in the liver as confirmed using the terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling method and DNA fragmentation assay. These results suggest that acanthoic acid protects against D-galactosamine/lipopolysaccharide-induced fulminant liver failure at least in part by a mechanism associated with the down-regulation of TNF-alpha secretion.

Goats and sewing machines

<h3>Objective</h3> Stem cell transplantation provides a promising alternative for the treatment of fulminant hepatic failure (FHF). However, it lacks fundamental understanding of stem cells’ activities. Our objective was to clarify stem cell-recipient interactions for overcoming barriers to clinical application. <h3>Design</h3> We used an in-house large-animal (pig) model of FHF rescue by human bone marrow mesenchymal stem cells (hBMSCs) and profiled the cells’ activities. The control and transplantation groups of pigs (n=15 per group) both received a D-galactosamine (D-Gal) injection (1.5 g/kg). The transplantation group received hBMSCs via intraportal vein infusion (3×10⁶ cells/kg) immediately after D-Gal administration. The stem cell-recipient interactions were quantitatively evaluated by biochemical function, cytokine array, metabolite profiling, transcriptome sequencing and immunohistochemistry. <h3>Results</h3> All pigs in the control group died within an average of 3.22 days, whereas 13/15 pigs in the transplantation group lived &gt;14 days. The cytokine array and metabolite profiling analyses revealed that hBMSC transplantation suppressed D-Gal-induced life-threatening cytokine storms and stabilised FHF within 7 days, while human-derived hepatocytes constituted only ∼4.5% of the pig hepatocytes. The functional synergy analysis of the observed profile changes indicated that the implanted hBMSCs altered the pigs’ cytokine responses to damage through paracrine effects. Delta-like ligand 4 was validated to assist liver restoration in both pig and rat FHF models. <h3>Conclusions</h3> Our results delineated an integrated model of the multifaceted interactions between stem cells and recipients, which may open a new avenue to the discovery of single molecule-based therapeutics that simulate stem cell actions.

Improvement of Experimentally Induced Hepatic and Renal Disorders in Rats using Lactic Acid Bacteria‐fermented Soybean Extract (Biofermentics™)

The effects of lactic acid bacteria-fermented soybean extract (Biofermentics™; BF) on experimental models of hepatic and renal disorders were investigated in vivo and in vitro. In rat, hepatitis induced by feeding of deoxycholic acid (DCA, 0.5 wt/wt, n = 6) or intraperitoneal injection of d-galactosamine (GMN, 500 mg/body wt, n = 6), the increase in serum AST (aspartate aminotransferase) and ALT (alanine aminotransferase) levels were inhibited significantly (P < 0.05) by feeding a diet containing 5% dried BF. Moreover, the BF-administered rat group showed lower concentrations of blood urea nitrogen and a larger amount of urine as compared with values in the control group. Pretreatment of primary cell cultures of rat hepatic and renal cells with BF prior to exposure to dichromate (K2Cr2O7) resulted in a marked decrease of dichromate-induced cytotoxicity as evaluated by the leakage of lactate dehydrogenase The levels of dichromate-induced lipid peroxidation, as monitored by malondialdehyde formation, were also reduced by pretreatment of hepatocytes with BF. These results suggest that BF may play a role in hepatic and renal disorders, and may be useful for maintaining health in humans as well.