• Journal of Yeungnam Medical Science
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• 제36권2호
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• pp.67-77
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• 2019

The paradigm of chronic liver diseases has been shifting. Although hepatitis B and C viral infections are still the main causes of liver cirrhosis and hepatocellular carcinoma (HCC), the introduction of effective antiviral drugs may control or cure them in the near future. In contrast, the burden of nonalcoholic fatty liver disease (NAFLD) has been increasing for decades, and 25 to 30% of the general population in Korea is estimated to have NAFLD. Over 10% of NAFLD patients may have nonalcoholic steatohepatitis (NASH), a severe form of NAFLD. NASH can progress to cirrhosis and HCC. NASH is currently the second leading cause to be placed on the liver transplantation list in the United States. NAFLD is associated with obesity, type 2 diabetes, dyslipidemia, and metabolic syndrome. The pathophysiology is complex and associated with lipotoxicity, inflammatory cytokines, apoptosis, and insulin resistance. The only proven effective treatment is weight reduction by diet and exercise. However, this may not be effective for advanced fibrosis or cirrhosis. Therefore, effective drugs are urgently needed for treating these conditions. Unfortunately, no drugs have been approved for the treatment of NASH. Many pharmaceutical companies are trying to develop new drugs for the treatment of NASH. Some of them are in phase 2 or 3 clinical trials. Here, pharmacologic therapies in clinical trials, as well as the basic principles of drug therapy, will be reviewed, focusing on pathophysiology.

• Natural Product Sciences
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• 제22권4호
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• pp.231-237
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• 2016

Prolonged alcohol consumption causes alcoholic liver damage due to the generation of reactive oxygen species, the accumulation of fatty acids, and an increase in inflammatory cytokines in the liver. In this study, the protective effect of a fruit extract of Paeonia anomala (FEPA) against chronic alcohol-induced liver damage was evaluated in Sprague-Dawley rats fed an ethanol or a control Lieber-DeCarli diet for 5 weeks to induce alcoholic liver damage. FEPA (50, 25, and 10 mg/kg body weight/day) as well as the reference control silymarin (25 mg/kg body weight/day) were administered along with the ethanol diet. FEPA protected against increases in alanine aminotransferase and aspartate aminotransferase in serum and attenuated alcohol-induced increases in triglycerides, tumor necrosis factor alpha, thiobarbituric acid-reactive substances, and cytochrome P450 2E1 enzyme activity in the liver compared with the group treated with ethanol only. Anti-oxidative defenses such as the total glutathione level and glutathione peroxidase activity were increased by FEPA treatment. These results suggest that FEPA exerts protective effects against chronic alcohol-induced liver damage by attenuating hepatosteatosis and pro-inflammatory cytokine production and enhancing anti-oxidative defense mechanisms in the liver.

• The Korean Journal of Physiology and Pharmacology
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• 제17권3호
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• pp.209-216
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• 2013

Soybean polyunsaturated phosphatidylcholine (PC) is thought to exert anti-inflammatory activities and has potent effects in attenuating acute renal failure and liver dysfunction. The aim of this study was to investigate the effects of PC in protecting multiple organ injury (MOI) from lipopolysaccharide (LPS). Six groups of rats (N=8) were used in this study. Three groups acted as controls and received only saline, hydrocortisone (HC, 6 mg/kg, i.v.) or PC (600 mg/kg, i.p.) without LPS (15 mg/kg, i.p.) injections. Other 3 groups, as the test groups, were administered saline, HC or PC in the presence of LPS. Six hours after the LPS injection, blood and organs (lung, liver and kidney) were collected from each group to measure inflammatory cytokines and perform histopathology and myeloperoxidase (MPO) assessment. Serum cytokines (TNF-${\alpha}$, IL-6 and IL-10) and MPO activities were significantly increased, and significant histopathological changes in the organs were observed by LPS challenge. These findings were significantly attenuated by PC or HC. The treatment with PC or HC resulted in a significant attenuation on the increase in serum levels of TNF-${\alpha}$ and IL-6, pro-inflammatory cytokines, while neither PC nor HC significantly attenuated serum levels of IL-10, anti-inflammatory cytokine. In the organs, the enhanced infiltration of neutrophils and expression of ED2 positive macrophage were attenuated by PC or HC. Inductions of MPO activity were also significantly attenuated by PC or HC. From the findings, we suggest that PC may be a functional material for its use as an anti-inflammatory agent.

• Asian-Australasian Journal of Animal Sciences
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• 제27권5호
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• pp.749-756
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• 2014

The present study was carried out to investigate the effects of dietary antioxidants on pro-inflammatory cytokines, heat shock protein (HSP) and antioxidant status in broiler chicks under summer conditions. A total of 162, 3-d-old broiler chicks were randomly assigned to a basal diet (CON) and the basal diet supplemented with vitamin C (200 mg/kg diet, VCD) or vitamin E (100 mg/kg, VED) until 35 day of age. All birds were exposed to summer diurnal heat stress at average daily fluctuations of temperature between $32^{\circ}C$ to $34^{\circ}C$ at day to $27^{\circ}C$ to $29^{\circ}C$ at night for the entire feeding periods. There was no significant difference in body weight, feed to gain ratio and the relative organ weight except the thymus in response to dietary vitamin C or E supplementation. However, the mRNA expression of interleukin (IL)-$1{\beta}$, IL-6, interferon (IFN)-${\gamma}$, Toll like receptor (TLR)-4 and HSP70 in the liver of birds fed diet containing vitamin C significantly (p<0.05) decreased compared with those in birds fed basal diet. Dietary vitamin E also showed a significant (p<0.05) decrease in the mRNA expression of IL-6 and HSP70 compared with a basal diet. Total antioxidant status (TAS) in serum of birds fed vitamin C supplemented diet was significantly (p<0.05) higher with than that in birds a basal diet. Lipid peroxidation in serum and liver resulted in a significant (p<0.05) decrease in response to dietary vitamin C or E supplementation. In conclusion, dietary supplementation with antioxidant vitamins, especially vitamin C resulted in a significant decrease in the mRNA expression of pro-inflammatory cytokines and HSP70, and higher antioxidant parameters than that of birds on the basal diet under summer conditions.

• 한국자원식물학회지
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• 제24권5호
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• pp.604-612
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• 2011

씀바귀추출물이 LPS shock 염증반응에서 항염증효과에 미치는 영향을 검토하기 위하여 생체 및 세포배양실험에서 전염증성 cytokine들의 생성과 혈액 내 생물학적 수치를 조사했다. 그 결과 LPS 염증유도 rat에서 씀바귀 추출물은 혈액 내 전염증성 cytokines 들, 즉 IL-$1{\beta}$, IL-6 및 TNF-${\alpha}$의 생산을 저해하고, 한편으로는 IL-10의 생산을 촉진하였다. 간장 IL-$1{\beta}$ 및 IL-6의 농도는 씀바귀추출물 처리군이 대조군보다 유의하게 낮은 값을 나타내었으나, TNF-${\alpha}$ 및 IL-10의 농도는 모든 처리군 간에 유의한 차이를 나타내지 않았다. Raw 264.7 cell의 세포배양실험에서는 TNF-${\alpha}$의 농도가 유의한 차이를 나타내지는 않았지만, 3개 cytokine 모두가 씀바귀 투여량이 증가함에 따라 감소하는 경향을 보였다. IL-10의 농도는 씀바귀 처리군 들 모두가 높은 경향을 나타내었다. 혈액 내 total protein 및 albumin의 농도는 대조군과 유의한 차이를 나타내지는 않았으나, 씀바귀추출물 처리 군에서 높은 경향을 보였다. 이상의 결과들을 종합해 보면 씀바귀 추출물에는 항염증반응에 관여하는 기능성물질이 내재하고 있음을 시사해 준다.

• Asian-Australasian Journal of Animal Sciences
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• 제24권10호
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• pp.1440-1446
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• 2011

The study investigated the effects of dietary Vitamin E (VE) on nitric oxide (NO) metabolism, immune function and analyzed the correlation between NO free radical and cytokines (IL-2 and IL-6) in broilers. One hundred and fifty 2-week-old broilers were randomly divided into three groups. Control group and lower VE ($VE^-$) group were provided with a basic diet supplemented with 12.55 mg/kg VE and 2.55 mg/kg VE for 30 days, respectively. Higher VE ($VE^{-}-VE^+$) group was supplemented with 2.55 mg/kg VE in the first 15 days and then 32.55 mg/kg VE in the next 15 days. Five broilers in each group were then sacrificed on the 5th, 10th, 15th, 20th, 25th and 30th days, respectively, and the content of NO free radical, superoxide dismutase (SOD), glutathione peroxidase (GSHPx), malondialdehyde (MDA) and cytokines, IL-2 and IL-6, were measured. The results showed that lower VE could decrease growth performance of broilers while higher VE could increase growth performance and eliminate differences resulted from feeding lower VE dietary in early stages (p<0.05). Compared with the control group, lower VE could increase significantly NO and MDA concentration, and increase IL-2 concentration in serum (p<0.05). Higher VE could significantly increase activities of SOD and glutathione GSH-Px (p<0.05). IL-2 is positively correlated with NO in heart (p<0.05) and IL-6 is negatively correlated with NO in liver (p<0.05) and heart (p<0.01). These results indicate that dietary VE could regulate antioxidant capacity and NO metabolism of broilers and higher VE-supplemented diet could directly decrease production of IL-2.

• Molecules and Cells
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• 제44권12호
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• pp.893-899
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• 2021

BLT2 is a low-affinity receptor for leukotriene B₄, a potent lipid mediator of inflammation generated from arachidonic acid via the 5-lipoxygenase pathway. The aim of this study was to investigate whether BLT2 plays any role in sepsis, a systemic inflammatory response syndrome caused by infection. A murine model of cecal ligation and puncture (CLP)-induced sepsis was used to evaluate the role of BLT2 in septic inflammation. In the present study, we observed that the levels of ligands for BLT2 (LTB₄ [leukotriene B₄] and 12(S)-HETE [12(S)-hydroxyeicosatetraenoic acid]) were significantly increased in the peritoneal lavage fluid and serum from mice with CLP-induced sepsis. We also observed that the levels of BLT2 as well as 5-lipoxygenase (5-LO) and 12-LO, which are synthesizing enzymes for LTB₄ and 12(S)-HETE, were significantly increased in lung and liver tissues in the CLP mouse model. Blockade of BLT2 markedly suppressed the production of sepsis-associated cytokines (IL-6 [interleukin-6], TNF-α [tumor necrosis factor alpha], and IL-1β [interleukin-β] as well as IL-17 [interleukin-17]) and alleviated lung inflammation in the CLP group. Taken together, our results suggest that BLT2 cascade contributes to lung inflammation in CLP-induced sepsis by mediating the production of inflammatory cytokines. These findings suggest that BLT2 may be a potential therapeutic target for sepsis patients.

• 대한한의학회지
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• 제24권1호
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• pp.190-201
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• 2003

Object : This study was designed to investigate the effects of Chungganhaeju-tang (Qingganjiejiu-tang) on cytotoxicity, growth inhibition, apoptosis and expression of cytokine in damaged HepG2 cells. Method : Toxicity on HepG2 cell induced by ethanol and acetaldehyde was measured for viability, cell growth, DNA replication and generation of apoptosis and cytokine. The recovery of the cell activity by Chungganhaeju-tang was estimated for the measured parameters using PCR with different cycle numbers, DNA gel-electrophoresis, and densitometric analysis, Results : Chungganhaeju-tang improves the recovery of HepG2 cells damaged by ethanol or acetaldehyde. The suppressed DNA synthesis of the cell damaged by ethanol or acetaldehyde is improved by Chungganhaeju-tang. A liver-protection effect was shown by the reduction of apoptosis and $TNF-{\alpha},{\;}IL-1{\beta}$ expressions that are induced by ethanol or acetaldehyde. Conclusion : The result indicates that Chungganhaeju-tang reduces toxicity induced by ethanol or acetaldehyde and recovers damaged liver function.

• 한국수의병리학회:학술대회논문집
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• 한국수의병리학회 2003년도 추계학술대회초록집
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• pp.16-16
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• 2003

Hepatic fibrosis is a common response to various chronic hepatic injuries and occurs as a consequence of the transformation of hepatic stellate cells into myofibroblasts (MFBs) producing abnormal extracellular matrix which is mainly induced by transforming growth factor-beta (TGF-${\beta}$), especially TGF-${\beta}$1 [1,2]. As the liver becomes fibrotic, there are both quantitative and qualitative changes in several pathological markers related to the hepatic fibrosis. These fibrotic markers in liver are mainly consisted of several proteins and cytokines, but sometimes included specific type cells. The aim of this study was to detect expression and change of markers (TGF-${\beta}$, mallory body, cytokeratin, ${\alpha}$-SMA, hypoxia, collagen) during hepatic fibrogenesis. (omitted)

• Journal of Veterinary Science
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• 제22권3호
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• pp.34.1-34.7
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• 2021

Anti-lipopolysaccharide (LPS) antibody administration has the potential benefits of neutralizing and consequently controlling rumen-derived LPS during subacute ruminal acidosis. Four Holstein bulls were used in this crossover study with a 2-week wash-out period. Anti-LPS antibody (0 or 4 g) was administered once daily for 14 days. Significantly lower ruminal LPS and higher 1-h mean ruminal pH were identified in the 4 g group. However, blood metabolites, acute-phase proteins, cytokines, and hepatic transcriptomes were not different between the two groups. Therefore, anti-LPS antibody administration mitigated ruminal LPS release and pH depression without accompanying responses in acute-phase inflammation or hepatic transcriptomic expression.