• Asian Pacific Journal of Cancer Prevention
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• v.15 no.23
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• pp.10413-10420
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• 2015

Side effects are an unavoidable consequence of chemotherapy drugs, during which liver injury often takes place. The current study was designed to investigate the protective effect of Astragalus polysaccharides (APS) against the hepatotoxicity induced by frequently-used chemical therapy agents, cyclophosphamide (CTX), docetaxel (DTX) and epirubicin (EPI)) in mice. Mice were divided into five groups, controls, low or high dose groups ($DTX_L$, $CTX_L$, $EPI_L$ or $DTX_H$, $CTX_H$, $EPI_H$), and low or high dose chemotherapeutics+APS groups ($DTX_L$+APS, $CTX_L$+APS, $EPI_L$+APS or $DTX_H$+APS, $CTX_H$+APS, $EPI_H$+APS). Controls were treated with equivalent normal saline for 28 days every other day; low or high dose group were intraperitoneal (i.p) injected with low or high doses of CTX, DTX and EPI for 28 days every other day; low or high dose chemotherapeutics+APS group were separately intraperitoneal (i.p) injected with chemotherapeutics for 28 days every other day and i.p with APS (100 mg/kg) for 7 days continually from the 22th to the 28th days. The body weight, serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), histopathological features, and ultrastructure morphological change of liver tissues, protein expression level of caspase-3 were estimated at different time points. With high dose treatment of DTX, CTX and EPI, weight gain was inhibited and serum levels of ALT and AST were significantly increased. Sections of liver tissue showed massive hepatotoxicity in $CTX_H$ group compared to the control group, including hepatic lobule disorder, granular and vacuolar degeneration and necrosis in hepatic cells. These changes were confirmed at ultrastructural level, including obvious pyknosis, heterochromatin aggregation, nuclear membrane resolution, and chondrosome crystal decrease. Western blotting revealed that the protein levels of caspase-3 increased in $CTX_H$ group. The low dose groups exhibited trivial hepatotoxicity. More interestingly, after 100 mg/kg APS, liver injury was redecued not only regarding serum transaminase activities (low or high dose chemotherapeutics+APS group), but also from pathological and ultrastructural changes and the protein levels of caspase-3 ($CTX_H$+APS group). In conclusion, DTX, CTX and EPI induce liver damage in a dose dependent manner, whereas APS exerted protective effects.

• Journal of Preventive Medicine and Public Health
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• v.24 no.3 s.35
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• pp.287-304
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• 1991

Tolerance to several toxic effects of cadmium, including lethality has been shown following pretreatment with cadmium and zinc. This study was designed to determine if tolerance also develops to Cd-induced hepatotoxicityandrenaltoxicity. Three groups of rats (A, B, C), each consisting of 16 rats, were studied and each group was divided into four subgroups (1, 2, 3, 4), 4 rats for each subgroup. Rats were subcutaneously pretreated with saline (A), $CdCl_2$ (0.5 mg/kg, B), and $ZnCl_2$ (13.0 mg/kg, C) during time periods of $1{\sim}6$ weeks. At the end of the period, rats were challenged with $CdCl_2$ (3.0, 6.0 and 9.0 mg/kg, ip). After giving the challenge dose, cadmium and metallothionein (MT) concentrations were determined and also observed the histologic change in liver and kidney. The concentration of cadmium in liver and kidney increased dose-dependently to the challenge dosage. These da indicate the kidney is a major target organ of chronic cadmium poisoning, and suggest that cadmium induced hepatic injury, via release of Cd-MT, may play an important role in the nephrotoxicity observed in response to long-term exposure to cadmium. In addition, histologic examination of group $A_2,\;A_3\;and\;A_4$ revealed moderate to severe cadmium toxicity, evidenced by infiltration of inflammatory cells, cell swelling, pyknosis, enlarged sinusoids and necrosis in liver, and tubule cell necrosis and degeneration in kidney. However, MT concentrations in liver and kidney were increased by the pretreatment of $CdCl_2$ and $ZnCl_2$, and their morphological findings were not significantly changed, comparing with control group. Higher MT concentration in liver and kidney observed in the pretreated groups constitutes a plausible explanation of the protective effects of pretreatment against the cadmium toxicity after challenge dosing.

• The Journal of Internal Korean Medicine
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• v.29 no.1
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• pp.200-218
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• 2008

Objectives : The purpose of this study was to investigate the effects of Injinchunggan-tang (Yinchenchinggan-tang) on DMN-induced liver damage by applying proteomics. Materials and Methods : Sprague-Dawley rats were used in this experiment and were divided into the normal group (normal saline), the control group (DMN) and the sample group (DMN+IJCGT). DMN was injected i.p. once a day three times a week for 3 weeks in the control group. Normal saline instead of DMN was administered to the normal group. In the sample group, Injinchunggan-tang (Yinchenchinggan-tang) extract was orally administered once a day for 10 days after DMN was induced. The livers of each group were processed and analyzed by histology, Western blot, $Oxyblot^{TM}$, CBB and 2-dimensional electrophoresis. Results : In the histological findings of the liver, IJCGT reduced collagen deposition and liver damage in DMN-induced hepatic fibrosis. IJCGT increased MMP-13 protein production assessed by western blot. Protein oxidation induced by DMN treatment was decreased by IJCGT. In the 2-dimensional electrophoresis finding, the level of the increased proteins induced by DMN treatment such as GRP 75, 58kDa glucose regulated protein and heat shock 70kDa protein 5 were decreased by IJCGT. IJCGT was considered to have the protective effects on hepatotoxicity induced by DMN. In the 2-dimensional electrophoresis finding, the level of increased oxidized proteins such as heat shock 70 protein, mitochondrial malonyltransferase, calreticulin precursor, actin, NADP-isocitrate dehydrogenase, ankyrin repeat and SOCS box protein 11 were decreased by IJCGT. IJCGT was considered to have protective effect on the protein production induced by DMN treatment. Conclusion : Injinchunggan-tang (Yinchenchinggan-tang) exerts an inhibitory effect against the fibrosis and protein oxidation induced by DMN treatment in the rat liver. IJCGT was considered to have protective effects on the hepatotoxicity and protein production induced by DMN treatment.

• Journal of Food Hygiene and Safety
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• v.33 no.1
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• pp.77-82
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• 2018

This study was carried out to investigate the effect of natural Eriobotrya japonica Lindl. vinegar on the liver protective effect of animals exposed to carbon tetrachloride. Eriobotrya japonica Lindl. vinegar (200 mg/kg) was administered at the same time for 28 days, and hepatotoxicity was induced by intraperitoneal injection of carbon tetrachloride on the $29^{th}$ day. The aspartate aminotransferase and alanine aminotransferase levels were significantly decreased (p < 0.001) and the superoxide dismutase and catalase activities were significantly increased (p < 0.001) in the Eriobotrya japonica Lindl. vinegar group compared to the control group. Histopathological observations showed that the Eriobotrya japonica Lindl. vinegar showed hepatic cell structure similar to normal group, and these results showed that it had an effect of suppressing and protecting the damage of liver cell. Therefore, Eriobotrya japonical Lindl. vinegar is considered to be a healthy functional food of the liver.

• The Korea Journal of Herbology
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• v.33 no.1
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• pp.37-46
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• 2018

Objectives : Liver disease is an inflammatory reaction caused by oxidative stress, viral, alcohol, and drug properties. Inflammatory reaction causes hepatitis and chronic hepatitis is persistent, it progresses to liver fibrogenesis and liver cancer. The aim of this study was to confirm the hepatoprotective effect of Tongyuhwalhyeol-tang(Tongqiaohuoxue Decoction) (TH) and Gamtongyuhawlhyeol-tang(GTH) in TAA-induced liver injury animal model. Methods : The antioxidant activities were evaluated through in vitro experiments, such as 1, 1-diphenyl-2-picrylhydrazyl (DPPH) and 2, 2'-azinobis-3-ethyl-benzothiazoline-6-sulfonic acid (ABTS) radical scavenging assays, total polyphenol and total flavonoid content measurement. To confirm the liver protective effect, induced by Thioacetamide (TAA) for 3 days injection at 200 mg/kg rats. TH and GTH were treated 3 days at 200 mg/kg/day. The changes of reactive oxygen species (ROS), peroxynitrite ($ONOO^-$), alanine aminotransferanse (ALT) and aspartate aminotransferase (AST) in serum were analyzed after experiment. Also, expression of anti-inflammation, anti-oxidant related proteins were investigated by western blot analysis. Results : TH was inhibited the antioxidant activities. In the TAA-induced rat, TH decreased ROS, $ONOO^-$, ALT, AST level in serum. Inflammation related protein expressions increased in TAA-induced rat compared to normal rat. However, TH group inhibited the down expression of these proteins. Also, anti-oxidant related protein expressions increased in TH group compared TAA-induced rat. Conclusion : Therefor, these results suggested that TH provided hepatoprotective effects on the hepatic injury leading to the reduction of inflammatory response. In addition, the effect of TH was superior to that of GTH.

• YAKHAK HOEJI
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• v.56 no.2
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• pp.99-107
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• 2012

The protective effect of AI-1367 (Alnus japonica extract) on liver injury was investigated. Primary rat hepatocyte intoxication was induced by tert-butyl hydroperoxide (tBH), carbon tetrachloride ($CCl_4$), or D-glactosamine (D-GalN). Liver injury was induced by $CCl_4$, D-GalN or MCD (methionine choline deficient)-diet in mouse. The cellular leakage of lactate dehyrogenase and cell viability followed by the treatment of hepatotoxicants were significantly improved by AI-1367 treatment at a concentration range of 5~50 ${\mu}g/ml$ for tBH, 5~50 ${\mu}g/ml$ for D-GalN, and 5~100 ${\mu}g/ml$ for $CCl_4$, respectively. Treatment with AI-1367 (20, 10, 5 mg/kg, p.o.) on liver injury induced by subcutaneous injection of $CCl_4$ or D-GalN reduced significantly the levels of aspartate transaminase and alanine transaminase in serum. Histological observations revealed that fatty acid changes, hepatocyte necrosis and inflammatory cell infiltration in $CCl_4$ (D-GalN)-induced liver injury was improved by administration of AI-1367. AI-1367 treatment (10, 5, 2.5 mg/kg, p.o.) also significantly recovered the body weight change and serum levels of aspartate transaminase, alanine transaminase and triglyceride in liver injury induced by MCD diet. From these results, AI-1367 shows protective effects against tBH, $CCl_4$, D-GalN, or MCD diet-induced hepatotoxicity in vitro or in vivo.

• Herbal Formula Science
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• v.16 no.2
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• pp.183-191
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• 2008

Acetaminophen (N-acety1-p-aminophenol, paracetamol) is widely used as an over-the-counter analgesic and antipyretic drug. Intake of a over dose of acetaminophen may result in severe hepatic necrosis. In this study, we investigated the liver damage in mice using single dose (300 mg/kg) of acetaminophen and the possible protective effects of administration (50-200 mg/kg body weight) of SB-Ex on acetaminophen-induced liver damage in mice. The alanine aminotransferase (ALT), and aspartate aminotransferase (AST) activities were determined in the plasma of mice. The effect of SB-Ex on lipid peroxidation product thiobarbituric reacting substances (TBARS) and some antioxidant enzymes superoxide dismutase (SOD), catalase, d-aminolevulinate dehydratase (${\sigma}$-ALA-D) activities, and gluthathione peroxidase (GPx), were also evaluated in the mouse liver homogenate. Acetaminophen caused liver damage as evident by statistically significant increased in plasma activities of AST and ALT. There were general statistically significant losses in the activities of SOD, catalase, ${\sigma}$-ALA-D, and GPx and an increase in TBARS in the liver of acetaminophen-treated group compared with the control group. However, SB-Ex was able to counteract these effects. These results suggest that SB-Ex can act as hepatoprotectives against acetaminophen toxicity and is a good candidate for further evaluation as an effective chemotherapeutic agent.

• Biomolecules & Therapeutics
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• v.2 no.2
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• pp.206-212
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• 1994

The present study was performed to determine the protective effect of G009 on liver damage induced bv ethanol $CCl_4$ and thioacetamide in rats. In acute fatty liver animal model induced by ethanol, triglyceride accumulation was markedly decreased to the normal control level by 25 mg/kg G009 treatment. In addition, G009 significantly reduced serum ALT and AST levels in $CCl_4$-induced acute hepatitis animals. Treatment of G009 to the acute hepatitis rats induced by thioacetamide resulted in a dose dependent reduction of serum ALT level as well as AST level up to the normal control level. These protective effects of G009 were confirmed by histological examinations of the liver. These results suggested that G009 could be effective for the protection from the liver damage induced by ethanol, $CCl_4$and thioacetamide.

• International Journal of Industrial Entomology and Biomaterials
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• v.2 no.1
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• pp.15-18
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• 2001

Silk fibroin (SF) derided from the domestic silk worm, bombyx mori, is the natural protein and widely used as bio-functional materials as well as apparels. We studied the livers protective effect of SF from alcohol-induced hepatotoxicity in the alcohol preference mouse. To increase more absorption of SF in experimental animals, molecular weight of SF was lowered by 2N of HCI aqueous solution at 10$0^{\circ}C$ for 48 hrs. SF was added to liquid diet with alcohol and fed to the alcohol preference mice for 4 weeks. To assess the liver function, the concentration of alanine aminotransferase (AlT), aspartate aminotransferase (AST) and cholesterol present in either blood or liver tissue were measured. As compared with non-SF treated groups the SF-treated showed significantly low concentrations of ALT, AST, cholesterol and triacylglycerol values, respectively. Histopathological examination revealed that the extent of hepatocyte injury in the SF-treated group was reduced when it was compared with non SF-treated group. These results suggest that SF may have liver protective effects against alcohol-induced hepatotoxicity.

• Korean Journal of Veterinary Research
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• v.36 no.2
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• pp.313-325
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• 1996

Experiments were undertaken to examine the ability of selenium to protect against alcohol and/or paraquat-induced hepatotoxicity and to examine the additive effect between alcohol and paraquat. Protective effect against hepatotoxic functions was measured in serum from alcohol(15% v/v), paraquat(200ppm), alcohol and paraquat, and combination of sodium selenite(4ppm) in drinking water-fed guinea pigs ad libitum for 4 weeks. A total of 68 healthy 7-weeks-old male animals were assigned at random to 8 treatment groups(9~13 animals/group). Body and liver weight losses, and high serum concentrations in aspartate aminotransferase(AST), alanine aminotransferase(ALT, in only paraquat group), $\gamma$-glutamyltranspeptidase($\gamma$-GTP), cholesterol(Cho), creatinine, blood urea nitrogen(BUN), total bilirubin(TB), direct bilirubin(DB), total protein(TP), albumin and globulin as well as low values in alkaline phosphatase(ALP) and glucose were produced in a groups of alcohol or paraquat-fed. These values were not potentiated in a group given the combination of alcohol plus paraquat. Morphological changes in the liver were also observed in the alcohol or paraquat-fed group. Lipid droplet and cell swelling in the hepatocytes were observed in alcohol-fed guinea pig, especially Mallory's hyaline arounded hepatic vein. In the paraquat-fed guinea pig, lipid droplet, pyknosis and karyolysis were observed. When alcohol or paraquat was combined with selenium-fed, hyperplasia of Kupffer cell in liver were observed. However, the mean ALT, $\gamma$-GTP, Cho, BUN, TB, TP, albumin and globulin values were lower in groups given the combination of alcohol and/or paraquat plus selenium, compared with groups given alcohol and/or paraquat. Also, the ratio of liver weight to body weight and ALP values(exception of paraquat plus selenium group) were increased by selenium. These results suggest that an adequate selenium confers marked protection against alcohol and paraquat-induced hepatotoxicity.