• Toxicological Research
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• 제23권4호
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• pp.347-352
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• 2007

The protective effects of Rubus coreanum Miquel (RCM) extract against LPS-induced hepatotoxicity were studied in rats. Squrague-Dawley rats were intraperitoneally administered the RCM at 100 mg/kg per day for three weeks. Then single dose of LPS (5 mg/kg) was injected into rats. Four hours later, they were anesthesized with ether and dissected. We examined the levels of glutamate oxaloacetate transaminase (AST), glutamate pyruvate transaminase (ALT), alkaline phosphatase (ALP) and lactate dehydrogenase (LDH) in sera, superoxide dismutase (SOD) in mitochondrial fraction and catalase (CAT), glutathione peroxidase (GPx) in liver homogenate. LPS-treatment markedly increased the levels of AST, ALT, ALP, LDH and significantly decreased those of SOD, CAT and GPx. But RCM-pretreatment decreased the levels of AST, ALT, ALP and LDH by 57.9%, 37.4%, 62% and 69% respectively and increased those of SOD, CAT and GPx by 82.9%, 64.2% and 96.7% respectively. Subsequently, the protective effects of RCM was evaluated through histopathological examination of liver tissue. The LPS treatment increased the state of necrosis and cirrhosis surrounding the central veins (CV) and sinusoid, but RCM-treatment decreased the state of necrosis and cirrhosis in the liver tissue. These results demonstrated that protective effects of RCM against LPS-induced hepatotoxicity.

• 대한수의학회지
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• 제56권2호
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• pp.129-131
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• 2016

Five eastern great egrets with a history of ataxia, wry neck, and wet feathers were submitted to the Veterinary Diagnostic Center for pathologic examination. Slightly enlarged livers with diffuse white-grayish nodules were observed. Microscopically, the hepatic and lung parenchyma contained granulomatous lesions consisting of central necrosis. Some hearts showed myofiber necrosis with infiltration of histiocytes and heterophils. Partial 16SrRNA and gyrB gene sequences of all isolates showed high similarities (99-100%) to those of Salmonella (S.) enterica subsp. enterica. Based on pathological and molecular biological results, S. enterica subsp. enterica systemic infections were diagnosed in eastern great egrets of Korea.

• Molecular & Cellular Toxicology
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• 제1권4호
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• pp.275-280
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• 2005

Carbon tetrachloride ($CCl_4$) is well known hepatotoxicant. Its overdose cause severe centrilobular hepatic necrosis in human and experimental animals. We administered $CCl_{4}$ at low (0.2 mL/kg p.o.) and high (2 mL/kg p.o.) doses to mice. Mice were sacrificed at 24 h after administration. We evaluated liver toxicity by serum AST and ALT level and by microscopic observation. Using cDNA chip, we conducted gene expression analysis in liver. Mean serum activities of the hepatocellular leakage enzymes, ALT and AST, were significantly increased compare to control, respectively, in the low and high dose groups. H&E evaluation of stained liver sections revealed $CCl_{4}-related$ histopathological findings in mice. Moderate centrilobular hepatocellular necrosis was present in all $CCl_{4}$ treated mice. We found that gene expression pattern was very similar between low and high dose group. However, some stress related genes were differently expressed. These results could be a molecular signature for the degree of liver injury. Our data suggest that the degree of severity could be figure out by gene expression profiling.

• 생약학회지
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• 제23권2호
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• pp.96-105
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• 1992

The studies were attempted to evaluated the therapeutic effects of various fractions(ether, methanol, butanol) of Caragana chamlagu roots on the hyperlipemia induced by feeding the diet containing 1%, cholesterol and 0.5%, cholic acid in rats, and on the hyperglycemia induced by streptozotocin in rats. Also the preventive effects of these fractions were studies on the liver damage in $CCl_4-intoxicated$ rats. The followings were obtained as the results: 1.The butanol fraction was significantly shown to down the serum lipid level in 1%, cholesterol and 0.5%, cholic acid diet-feeding rats and streptozotocin-induced hyperglycemic rats. Cholesterol level in $CCl_4-intoxicated$ rats was reduced in the case of all pre-treated groups. 2.The serum glucose level of streptozotocin-induced hyperglycemic rats was significantly decreased by the administration of various fractions of C. chamlagu roots, and the lipid-peroxidation of pancreas was significantly decreased in the case of administration of these fractions. 3.The activates of s-GOT and s-GPT were decreased by the administration of various fractions, especially in butanol fraction, of C. chamlagu roots in the $CCl_4-intoxicated$ rats. The liver lipid-peroxidation was decreased by administration of 200mg/kg of these fractions in the $CCl_4-intoxicated$ rats. In histological observation, hepatic cellular necrosis and fatty acid deposit were increased remarkably by $CCl_4-intoxication$, but the pretreatment of various fractions of C. chamlagu roots improved the pathological change of parenchymatous cell necrosis and fatty change around centrilobular area of the control.

• Journal of Ginseng Research
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• 제43권1호
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• pp.10-19
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• 2019

Background: Frequent overdose of paracetamol (APAP) has become the major cause of acute liver injury. The present study was designed to evaluate the potential protective effects of ginsenoside Rk1 on APAP-induced hepatotoxicity and investigate the underlying mechanisms for the first time. Methods: Mice were treated with Rk1 (10 mg/kg or 20 mg/kg) by oral gavage once per d for 7 d. On the 7th d, allmice treated with 250mg/kg APAP exhibited severeliverinjury after 24 h, and hepatotoxicitywas assessed. Results: Our results showed that pretreatment with Rk1 significantly decreased the levels of serum alanine aminotransferase, aspartate aminotransferase, tumor necrosis factor, and interleukin-$1{\beta}$ compared with the APAP group. Meanwhile, hepatic antioxidants, including superoxide dismutase and glutathione, were elevated compared with the APAP group. In contrast, a significant decrease in levels of the lipid peroxidation product malondialdehyde was observed in the ginsenoside Rk1-treated group compared with the APAP group. These effects were associated with a significant increase of cytochrome P450 E1 and 4-hydroxynonenal levels in liver tissues. Moreover, ginsenoside Rk1 supplementation suppressed activation of apoptotic pathways by increasing Bcl-2 and decreasing Bax protein expression levels, which was shown using western blotting analysis. Histopathological observation also revealed that ginsenoside Rk1 pretreatment significantly reversed APAP-induced necrosis and inflammatory infiltration in liver tissues. Biological indicators of nitrative stress, such as 3-nitrotyrosine, were also inhibited after pretreatment with Rk1 compared with the APAP group. Conclusion: The results clearly suggest that the underlying molecular mechanisms in the hepatoprotection of ginsenoside Rk1 in APAP-induced hepatotoxicity may be due to its antioxidation, antiapoptosis, anti-inflammation, and antinitrative effects.

• 한방비만학회지
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• 제18권2호
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• pp.74-82
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• 2018

Objectives: The objective of this study is to investigate the effects of Silbi-um (SBU) extract on the alcoholic fatty liver induced by EtOH administration for 8 weeks. Methods: Male Sprague Dawley rats were used. All animals were randomly divided into 3 groups; Normal, EtOH and EtOH+SBU. The rats of EtOH group were daily treated with ethanol of 25% (v/v) for 8 weeks (n=10). EtOH+SBU group was orally treated with SBU water extract after ethanol administration (n=10). The rats of Normal group were treated with saline (n=10). After 8 weeks, the mean body weight, liver weight, and liver-body weight ratio were calculated. The serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) of all groups were measured. The morphological alterations were observed using hematoxylin and eosin (H&E) and Oil Red O staining. Moreover, the alteration of tumor necrosis $factor-{\alpha}$ ($TNF-{\alpha}$) levels were analyzed immunohistochemistrically. Results: The histological data showed that liver sections from EtOH group displayed severe steatosis. SBU extract significantly inhibited the progression of the alcoholic liver injury. The increased serum level of ALT and AST induced by ethanol administration were decreased by SBU extract. Furthermore, SBU extract significantly decreased the liver concentrations of $TNF-{\alpha}$. Conclusions: SBU water extract attenuated the alcohol induced fatty liver by improving hepatic lipid metabolism via suppression of $TNF-{\alpha}$ protein. SBU could be effective in protecting the liver from alcoholic fatty liver.

• 한국임상수의학회지
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• 제23권1호
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• pp.72-76
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• 2006

1년령의 암컷 잉글리쉬 코커스파니엘 견이 3개월 병력의 구토와 구토물의 재섭취, 그리고 체중감소로 내원하였다. 이 환자는 일반혈액 검사, 혈청화학 검사, 방사선 검사, 복수 분석, 담즙산 농도 측정, 탐색적 개복술, 그리고 사후 부검을 통한 간 생검으로 만성 간염 및 간경화증으로 진단되었다. 혈액 검사상 경미한 빈혈, 경미한 간효소치의 상승, CK치의 상승, 저알부민혈증을 동반한 저단백혈증이 관찰되었다. 복수는 분석을 통해서 누출성 복수인 것으로 판명되었다. 담즙산 농도를 측정해 본 결과(fasting; $174.4{\mu}mol/L$ and postprandial; $198.4{\mu}mol/L$)로부터 간기능 부전을 강하게 의심할 수 있었다. 방사선 검사상 복수가 관찰되었고 결국 탐색적 개복술을 실시하여 좌측엽 부위의 간 위축, 장간막 혈관 구조들의 팽창된 소견이 관찰되었다. 간 좌측 후엽모서리 부위에서 봉합법을 통해 생검을 실시하였다. 간 조직의 조직병리학적인 검사 결과 간 세포의 괴사, 동양 혈관의 확장, 동양 혈관 내 호중구의 침착, 그리고 간 세포질의 공포화 등이 관찰되었다. 환축은 저단백 사료 급여 그리고 특수보조제 (ursodeoxycholic acid, prednisolone, vitamine E and interferon)등을 사용하여 관리했다. 구토와 복수는 치료 후 사라졌다. 환축은 정기적으로 혈액 검사, 혈청 화학 검사, 방사선 검사 등을 실시하였다. 이 환축은 내과적인 치료를 받으며 18개월간 생존하였다가 폐사하였다. 사후 부검을 실시했고 조직병리학적인 검사가 시행되었으며 그 결과 간세포에 림프구의 침윤된 진행성의 간경화증으로 판정되었다.

• 동의생리병리학회지
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• 제19권1호
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• pp.174-178
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• 2005

정제 방법을 다르게 하여 추출된 죽력을 30일 동안 생쥐에 구강 투여한 후 혈액생화학적인 변화 및 간조직의 항산화효소 활성 및 조직학적 검색을 수행하였다. 실험군은 7개 군으로 구분하였다; 생리식염수를 투여한 10% 죽력(4mL/kg)을 투여한 실험군(B1, C1, D1), 그리고 30% 죽력(4mL/kg)을 투여한 실험군(B2, C2, D2). 혈액학적 검색 결과 D2군의 적혈구 수와 적혈구 용적이 대조군에 비하여 유의성있게(P<0.05) 감소하였다. Transaminase의 활성은 D2군에서 유의성있게(P<0.05) 증가하였으나, SOD와 catalase의 활성 또한 D군에서 유의성있게(P<0.01) 감소하였다. 조직병리학적 검색 결과 D군의 간조직은 지방공포화 뿐만 아니라 간세포 핵이 괴사되어 있었다. 이상의 결과로 보아 고온으로 추출한 죽력을 $108^{\cir}C$에서 2회 증류하여 정제한 죽력 D가 현저한 독성을 갖고 있음을 확인할 수 있었다.

• Molecular & Cellular Toxicology
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• 제3권3호
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• pp.177-184
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• 2007

As a possible feasibility of the extrapolation between in vivo and in vitro systems, we investigated the global gene expression from both mouse liver and mouse hepatic cell line treated with hepatotoxic chemical, acetaminophen (APAP), and compared between in vivo and in vitro genomic profiles. For in vivo study, mice were orally treated with APAP and sacrificed at 6 and 24 h. For in vitro study, APAP were administered to a mouse hepatic cell line, BNL CL.2 and sampling was carried out at 6 and 24 h. Hepatotoxicity was assessed by analyzing hepatic enzymes and histopathological examination (in vivo) or lactate dehydrogenase (LDH) assay and morphological examination (in vitro). Global gene expression was assessed using microarray. In high dose APAPtreated group, there was centrilobular necrosis (in vivo) and cellular toxicity with the elevation of LDH (in vitro) at 24 h. Statistical analysis of global gene expression identified that there were similar numbers of altered genes found between in vivo and in vitro at each time points. Pathway analysis identified glutathione metabolism pathway as common pathways for hepatotoxicty caused by APAP. Our results suggest it may be feasible to develop toxicogenomics biomarkers or profiles by comparing in vivo and in vitro genomic profiles specific to this hepatotoxic chemical for application to prediction of liver toxicity.

• 한국동물위생학회지
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• 제29권3호
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• pp.347-364
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• 2006

This study is concerned with assessment of diethylnitrosamine (DEN 0.01 %) induced liver cell carcinogenesis by measurement of changes preceding the development of neoplasms. Therefore, it was undertaken to investigate changes of liver-specific enzyme activities in Sprague-Dawley (SD) rats by ad libitum feeding of DEN. And also. the changes of hepatic morphology in SD rats were detected by haematoxylineosin stain and immunohistochemistry (PCNA). 5- Fluorouracil (5- FU) is one of the most widely used anticancer agents for digestive cancers including hepatocellular carcinoma, and is known to affect the cell cycle and induce apoptosis of cancer cells. In the present study, SD rats were given drinking water containing 0.01% diethylnitrosamine (DEN) for 8 weeks. Minor behavioral change, brittleness of hair and decreased amount of water and diet intake were observed in rats 4 weeks after DEN administration. The body and liver weights were significantly (p < 0.05) decreased in rats 11 weeks after DEN administration. The liver weight ratio to body weight was rather stable and not significantly decreased in the all treatment groups. The liver specific enzyme activities (AST, ALT, ${\gamma}$-GTP) were significantly increased in all treatment groups compared to control group (p < 0.05). Variable size of liver tumor and hepatomegaly were observed in rats treated with DEN after 10 weeks. Numerous vacuoles were seen on the midzonal and or peripheral areas of hepatic lobules. The large and polymorphological hepatocytes with eosinophilic cytoplasm or densely basophilic mitotic nucleoli were seen. Several proliferative small round cells were seen on vacuolated and necrotic areas in peripheral hepatic lobules or portal areas. PCNA-positive cells were seen on the vacuolated portal areas and peripheral areas of hepatic lobules in the areas of small round cells. We examined functional and morphological changes of livers by 5 - FU treatments on DEN -treated rat. The DEN -treated rats compared to 5 - FU -treated rats after DEN treatment for 8 weeks. The serum total protein and triglyceride were significantly (p < 0.05) decreased, and the liver enzyme activities of AST and ALT were significantly(p < 0.05) increased. After 8 weeks, in the non-5-FU -treated group, the size of liver tumor were varied and hepatomegaly were observed, hepatocellular vacuolization, necrosis and steatosis were observed on the midzonal and peripheral areas of hepatic lobules. The large and polymorphological hepatocytes were seen, the interlobular connective tissues were proliferated. PCNA positive cells were seen in the portal areas and peripheral areas of hepatic lobules in the non-5-FU-treated group. In hepatocytes, condensation of nuclear chromatin and vacuolization were observed, shape of the nuclei were irregular, the degraded nuclei and organelles were observed. The livers of rats in the 5 - FU treatment group were seen grossly brilliant, red-brown color, and the vacuolated and degenerated regions, hyperplastic nodules were not nearly observed. In the electron microscope, the cytoplasm of the hepatocytes contained a large number of mitochondria, rough endoplasmic reticulum, developed organelles surrounding nuclei. The above findings suggest that 5 - FU will be effective as anti -liver tumor drug.