• 한국환경농학회지
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• 제20권3호
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• pp.155-161
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• 2001

Paraquat와 bentazone이 횐쥐의 간조직과 NIH 3T3 섬유모세포에 미치는 독성과 그 독성에 대한 3-MC의 보상효과를 조사하기 위하여 NIH 373 섬유모세포에 적응한 후 경시적으로 MTT분석을 이용하여 세포독성을 측정하고 Sprague Dawley계 웅성 횐쥐에 paraquat와 bentazone단독 및 paraquat 및 bentazone과 3-MC를 병용투여한 후 경시적으로 관찰한 결과 paraquat와 bentazone은 NIH 3T3 섬유모세포에 대하여 $IC_{50}$값이 각각 1668.97 ${\mu}M$, 1506.97 ${\mu}M$으로 Borenfreund의 독성평가기준에 의하면 저독성이었다. Paraquat와 bentazone 단독투여군의 H&E 염색에서 3시간째에는 문맥 주위 세포들이 변성을 일으키고 별모양 세포들이 증가하였으나 12시간째에는 간소엽 전체의 세포들이 변성을 일으켰으며 48시간째에는 더욱 심한 변성이 일어났다. 특히 bentazone 투여 후 48시간째에는 핵농축현상이 뚜렷하였다. Best carmine 염색에서 glycogen 과립을 함유하는 간세포들도 3시간째에는 문맥주위의 세포들이, 12시간째에는 간소엽 전체의 간세포들이, 48시간째에는 전체의 간세포들이 함유하는 glycogen 과립량이 현저히 증가하였다. 3-MC를 paraquat와 bentazone과 동시에 투여한 군에서 3시간째와 12시간째에는 단독투여군과 유사하였으나 48시간째에는 bentazone과 3-MC 동시투여군의 문맥주위의 간세포들이 재생되는 경향이었으며 paraquat와 3-MC를 동시에 투여한 군에서는 중심정맥 주위의 세포들만이 glycogen과립을 함유하고 있어 단독 투여군과 뚜렷한 차이를 관찰할 수 있었다. 이 결론에서 3-MC는 paraquat와 bentazone에 의한 간세포의 독성을 경감시킬 수 있는 물질임을 알 수 있었다.

• 한국식품과학회지
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• 제41권5호
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• pp.597-601
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• 2009

간성상세포(HSC)는 간섬유화와 간경변에 중요한 역할을 한다고 알려져 있다. 간손상에 의해 둥근 모양의 간성상세포는 활성화되어 세포외기질(ECM)을 생산하는 myofibroblast와 같은 모양으로 활성화 된다. 활성화된 간성상세포의 특징은 빠른 증식 속도와 collagen과 같은 세포외 기질의 생산이다. 활성화된 간성상 세포의 제거방법은 apoptosis를 유도하는 것이다. 가자 추출물은 정상 간세포(rat primary hepatocyte), 간세포주(HepG2) 및 활성화된 간성상세포주인 T-HSC/Cl-6에 $1,000{\mu}g/mL$의 농도까지 처리하여 세포독성을 확인하였다. 그 결과 hepatocyte나 HepG2에서는 최고 농도에서도 독성이 없었으나 T-HSC/Cl-6는 U-shape 모양으로 사멸하는 것을 확인 하였다. T-HSC/Cl-6의 사멸이 apoptosis에 의한 것인지를 Annexin-V/PI double staining을 통하여 확인한 결과 apoptosis에 의해 T-HSC/Cl-6의 사멸이 일어나는 것을 확인하였다.

• 동아시아식생활학회지
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• 제23권1호
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• pp.44-52
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• 2013

This study investigated hepatic functional improvement and anti-fibrotic effects of water extracts of black tea. Male Sprague-Dawley rats were divided into four groups (normal, control, and two experimental subgroups: Ba, Bb) and observed for 3 weeks. Liver fibrosis in rats developed from carbon tetrachloride ($CCl_4$) administration, except for the normal group. Except for the normal and control group, the two experimental subgroups were fed water extracts of black tea. The food efficiency ratio significantly increased in the experimental group compared to the control group. The experimental group had a significantly lower liver weight compared to the control group. The ratio of liver weight to body weight was significantly lower in the experimental group than the control group. The levels of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, blood urea nitrogen, and low-density lipoprotein-cholesterol in serum significantly decreased in the experimental group compared to the control group. The values of hydroxyproline and malondialdehyde in liver were even lower in the experimental group than the control group. In observations on liver histology, weaker inflammation and fibrosis were observed in the experimental group compared to the control group. In conclusion, water extracts of black tea help hepatic cells keep their functions, restraining and protecting the liver from impairments caused by $CCl_4$ administration, and can be effective as anti-fibrotic agents.

• Molecules and Cells
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• 제44권2호
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• pp.116-125
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• 2021

Cardiovascular diseases (CVDs) are the most common cause of death in patients with nonalcoholic fatty liver disease (NAFLD) and dyslipidemia is considered at least partially responsible for the increased CVD risk in NAFLD patients. The aim of the present study is to understand how hepatic de novo lipogenesis influences hepatic cholesterol content as well as its effects on the plasma lipid levels. Hepatic lipogenesis was induced in mice by feeding a fat-free/high-sucrose (FF/HS) diet and the metabolic pathways associated with cholesterol were then analyzed. Both liver triglyceride and cholesterol contents were significantly increased in mice fed an FF/HS diet. Activation of fatty acid synthesis driven by the activation of sterol regulatory element binding protein (SREBP)-1c resulted in the increased liver triglycerides. The augmented cholesterol content in the liver could not be explained by an increased cholesterol synthesis, which was decreased by the FF/HS diet. HMG-CoA reductase protein level was decreased in mice fed an FF/HS diet. We found that the liver retained more cholesterol through a reduced excretion of bile acids, a reduced fecal cholesterol excretion, and an increased cholesterol uptake from plasma lipoproteins. Very low-density lipoproteintriglyceride and -cholesterol secretion were increased in mice fed an FF/HS diet, which led to hypertriglyceridemia and hypercholesterolemia in Ldlr-/- mice, a model that exhibits a more human like lipoprotein profile. These findings suggest that dietary cholesterol intake and cholesterol synthesis rates cannot only explain the hypercholesterolemia associated with NAFLD, and that the control of fatty acid synthesis should be considered for the management of dyslipidemia.

• Biomolecules & Therapeutics
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• 제30권5호
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• pp.391-398
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• 2022

Polyploidization is a process by which cells are induced to possess more than two sets of chromosomes. Although polyploidization is not frequent in mammals, it is closely associated with development and differentiation of specific tissues and organs. The liver is one of the mammalian organs that displays ploidy dynamics in physiological homeostasis during its development. The ratio of polyploid hepatocytes increases significantly in response to hepatic injury from aging, viral infection, iron overload, surgical resection, or metabolic overload, such as that from non-alcoholic fatty liver diseases (NAFLDs). One of the unique features of NAFLD is the marked heterogeneity of hepatocyte nuclear size, which is strongly associated with an adverse liver-related outcome, such as hepatocellular carcinoma, liver transplantation, and liver-related death. Thus, hepatic polyploidization has been suggested as a potential driver in the progression of NAFLDs that are involved in the control of the multiple pathogenicity of the diseases. However, the importance of polyploidy in diverse pathophysiological contexts remains elusive. Recently, several studies reported successful improvement of symptoms of NAFLDs by reducing pathological polyploidy or by controlling cell cycle progression in animal models, suggesting that better understanding the mechanisms of pathological hepatic polyploidy may provide insights into the treatment of hepatic disorders.

• 대한한의학회지
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• 제27권1호
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• pp.91-103
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• 2006

Objectives : Etiological studies of diabetes and its complications showed that oxidative stress might play a major role. Therefore, many effects have been fried to regulate oxygen free radicals for treating diabetes and its complications. Because Holotrichia has been known to be effective for the treatment of diabetes, the methanol extract of Holotrichia was tested for its effectiveness in reducing the oxidative stress induced by streptozotocin. Methods : Holotrichia was washed, dried in the shade and crushed. The crushed Holotrichia was extracted 3 times, each time with 3 volumes of methyl alcohol at $60^{\circ}C$ for 24h. The extract was filtered and evaporated under a reduced pressure using a rotary evaporator to yield 17 g. Holotrichia extract was oral-administed to the diabetic rats induced by streptozotocin 50 mg per 1 kg of body weight for 20 days. The efficacy of the Holotrichia extract was examined with regard to the enzymatic pathways involved in the oxygen free radical production and the glutathione balance. Results : The Effects of the methanol extract of Holotrichia in streptozotocin-induced diabolic rats with regards to body weight, blood glucose level, hepatic lipid peroxide level, hepatic superoxide anion radical content. hepatic xanthine oxidase activity and type conversion rate, hepatic glutathione level, hepatic aldose reductase activity, and hepatic sorbitol dehydrogenase activity were shown to be good enough to cure and prevent the diabetes and its complications. Conclusions : These results indicated that Holotrichia might reduce the oxidative stress in the tissues and organs by regulating the production of oxygen free radicals. Especially, Holotrichia might prevent and cure the diabetes and its complications by reducing the oxidative stress in the ${\beta}$-cells of pancreas. Some suggestions on biophoton experiments were made.

• Nutrition Research and Practice
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• 제10권6호
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• pp.623-628
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• 2016

BACKGROUND/OBJECTIVES: Obesity-induced steatohepatitis accompanied by activated hepatic macrophages/Kupffer cells facilitates the progression of hepatic fibrinogenesis and exacerbates metabolic derangements such as insulin resistance. Heme oxyganase-1 (HO-1) modulates tissue macrophage phenotypes and thus is implicated in protection against inflammatory diseases. Here, we show that the flavonoid quercetin reduces obesity-induced hepatic inflammation by inducing HO-1, which promotes hepatic macrophage polarization in favor of the M2 phenotype. MATERIALS/METHODS: Male C57BL/6 mice were fed a regular diet (RD), high-fat diet (HFD), or HFD supplemented with quercetin (HF+Que, 0.5g/kg diet) for nine weeks. Inflammatory cytokines and macrophage markers were measured by ELISA and RT-PCR, respectively. HO-1 protein was measured by Western blotting. RESULTS: Quercetin supplementation decreased levels of inflammatory cytokines ($TNF{\alpha}$, IL-6) and increased that of the anti-inflammatory cytokine (IL-10) in the livers of HFD-fed mice. This was accompanied by upregulation of M2 macrophage marker genes (Arg-1, Mrc1) and downregulation of M1 macrophage marker genes ($TNF{\alpha}$, NOS2). In co-cultures of lipid-laden hepatocytes and macrophages, treatment with quercetin induced HO-1 in the macrophages, markedly suppressed expression of M1 macrophage marker genes, and reduced release of MCP-1. Moreover, these effects of quercetin were blunted by an HO-1 inhibitor and deficiency of nuclear factor E2-related factor 2 (Nrf2) in macrophages. CONCLUSIONS: Quercetin reduces obesity-induced hepatic inflammation by promoting macrophage phenotype switching. The beneficial effect of quercetin is associated with Nrf2-mediated HO-1 induction. Quercetin may be a useful dietary factor for protecting against obesity-induced steatohepatitis.

• 대한한방내과학회지
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• 제37권3호
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• pp.442-452
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• 2016

Objectives: This study was performed to investigate the anti-lipogenic effect and the mechanism of Jungmanbunso-hwan extract (JMBSH) on a cellular model of non-alcoholic fatty liver disease (NAFLD) caused by palmitate in HepG2 cells.Methods: The JMBSH was prepared, andHepG2 cells were treated with various concentrations of JMBSH in order to perform an MTT assay. The HepG2 cells were cultivated in palmitate-containing media with or without extract of JMBSH. The intracellular lipid content in the HepG2 cells was examined. The effects of JMBSH on sterol regulatory element-binding transcription factor-1c (SREBP-1c), acetyl-CoA carboxylase (ACC), fatty acid synthase (FAS), stearoyl-CoA desaturase-1 (SCD-1), and AMP-activated protein kinase (AMPK) activation in HepG2 cells were measured.Results: JMBSH did not reduce HepG2 cell viability under 1,000 μg/mL. JMBSH considerably decreased intracellular lipid accumulation caused by palmitate in HepG2 cells. JMBSH repressed expression of SREBP-1c, which mediates the induction of lipogenic genes (ACC, FAS, and SCD-1). JMBSH also activated AMPK, which plays animportant role in the regulation of hepatic lipid metabolism.Conclusions: This study suggested that JMBSH relieves hepatic steatosis by repressing SREBP-1c, which mediates the induction of lipogenic genes. The anti-lipogenic effect of JMBSH may also be related to the activation of AMPK. Therefore, JMBSH could potentially be applied to NAFLD treatment after further clinical studies.

• Journal of Ginseng Research
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• 제36권3호
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• pp.248-255
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• 2012

Potential antioxidant effect of processed ginseng (sun ginseng, SG) on oxidative stress generated by tert-butyl hydroperoxide (t-BHP) was investigated in HepG2 cells. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and lactate dehydrogenase (LDH) leakage test demonstrated that SG dose-dependently prevents a loss of cell viability against t-BHP-induced oxidative stress. Also, SG treatment dose-dependently relieved the increment of activities of hepatic enzymes, such as aspartate aminotrasferase and alanine aminotransferase, and lipid peroxidation mediated by t-BHP treatment in HepG2 cells. SG increased the gene expression of antioxidant enzymes such as superoxide dismutase, catalase, and glutathione peroxidase. However, high dose of SG treatment caused decrease in mRNA level of glutathione peroxidase as compared to low dosage of SG-treated cells. The gene expression of glutathione reductase was found to be slightly increased by SG treatment. In addition, SG extract attributed its hepaprotective effect by inducing the mRNA level of bcl-2 and bcl-xL but reducing that of bax. But, the gene expression of bad showed no significant change in SG-treated HepG2 cells. These findings suggest that SG has hepatoprotective effect by showing reduction of LDH release, activities of hepatic enzymes and lipid peroxidation and regulating the gene expression of antioxidant enzymes and apoptosis-related molecules against oxdative stress caused by t-BHP in HepG2 cells.

• 환경생물
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• 제36권4호
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• pp.498-506
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• 2018

본 연구는 D-galactosamine에 의해 간 손상이 유도된 흰쥐에 다슬기(Semisulcospira libertina) 추출물이 손상된 간세포의 개선 및 회복에 미치는 효과에 관해 조사하였다. 다슬기 추출물은 간 손상에 따른 간 조직 내 국소적 지방 변성과 염증세포 침윤을 크게 감소시켜 대조군과 유사한 수준으로 회복시키는 경향을 나타내었다. 또한 다슬기 추출물은 간 손상 지표 효소인 AST와 ALT, LDH 및 ALP의 증가된 효소 활성을 대조군 수준으로 완화시키며, 간 조직 내 지질과 과산화지질의 함량을 감소시켜 간 손상으로 인한 혈중 효소 활성과 조직 내 지질 함량을 개선하는 것으로 조사되었다. 이와 더불어 다슬기 추출물은 염증반응을 촉진시켜 조직상해 및 괴사를 유도하는 $TNF-{\alpha}$의 발현을 억제시키며, 염증 시 세포를 보호하는 HO-1의 발현을 촉진시켜 염증 반응에서 손상된 세포를 대조군 상태의 세포로 회복시키는데 관여하는 것으로 조사되었다. 따라서 다슬기 추출물은 간조직의 괴사 및 섬유화를 회복시키고 혈액 내 효소의 활성과 조직 내 지질 함량을 개선할 뿐만 아니라 염증 반응 인자의 발현을 조절하고 있어 간 손상으로 인한 간세포의 개선 및 회복에 효과가 높은 기능성 소재로서의 가능성을 제시해 주고있다.