• Journal of Yeungnam Medical Science
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• 제40권2호
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• pp.115-122
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• 2023

Hepatic ischemia-reperfusion injury is a major complication of liver transplantation, trauma, and shock. This pathological condition can lead to graft dysfunction and rejection in the field of liver transplantation and clinical hepatic dysfunction with increased mortality. Although the pathological mechanisms of hepatic ischemia-reperfusion injury are very complex, and several intermediators and cells are involved in this phenomenon, oxidative stress and inflammatory responses are the key processes that aggravate hepatic injury. This review summarizes the current understanding of oxidative stress and inflammatory responses and, in that respect, addresses the therapeutic approaches to attenuate hepatic ischemia-reperfusion injury.

• 대한약침학회지
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• 제22권2호
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• pp.109-114
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• 2019

Objectives: Oxidative stress plays a central role in diabetes-induced complications. In the present study, the protevtive effect of Artemisia turanica (A. turanica) was evaluated against diabetes-induced liver oxidative stress and dysfunction. Methods: Fifty male Wistar rats were randomly divided into five groups: control, diabetic, diabetic + metformin, diabetic + A. turanica extract, and diabetic + A. turanica extract + metformin. Experimental diabetes was induced by a single-dose (55 mg/kg, intraperitoneally (ip)) injection of streptozotocin (STZ). Metformin (300 mg/kg) and A. turanica extract (70 mg/kg) were orally administrated three days after STZ injection for four weeks. The levels of malondialdehyde (MDA), total thiol content and superoxide dismutase (SOD) and catalase activities were measured in the liver tissue. Serum glucose concentration, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities were also determined. Results: In the diabetic group, serum glucose concentration, serum AST and ALT activities and liver MDA level were significantly higher while tissue total thiol content as well as catalase and SOD activities were lower, compared to the control group. Serum glucose in diabetic rats treated with metformin + A. turanica extract showed a significant decrease compared with the diabetic group. In all the A. turanica extract and metformin treated groups, serum ALT, tissue MDA level, total thiol content and SOD activity significantly improved compared with the diabetic rats. However, treatment of the diabetic rats only with metformin could not significantly change the activities of catalase and AST compared with the diabetic group. Conclusion: These findings suggested that A. turanica extract had a therapeutic effect on liver dysfuncyion and oxidative stress induced by diabetes, that may be probably due to its antioxidant and antiinflammatory effects.

• Toxicological Research
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• 제30권3호
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• pp.193-198
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• 2014

Degradation of glucose is aberrantly increased in hyperglycemia, which causes various harmful effects on the liver. Methylglyoxal is produced during glucose degradation and the levels of methylglyoxal are increased in diabetes patients. In this study we investigated whether methylglyoxal induces mitochondrial impairment and apoptosis in HepG2 cells and induces liver toxicity in vivo. Methylglyoxal caused apoptotic cell death in HepG2 cells. Moreover, methylglyoxal significantly promoted the production of reactive oxygen species (ROS) and depleted glutathione (GSH) content. Pretreatment with antioxidants caused a marked decrease in methylglyoxal-induced apoptosis, indicating that oxidant species are involved in the apoptotic process. Methylglyoxal treatment induced mitochondrial permeability transition, which represents mitochondrial impairment. However, pretreatment with cyclosporin A, an inhibitor of the formation of the permeability transition pore, partially inhibited methylglyoxal-induced cell death. Furthermore, acute treatment of mice with methylglyoxal increased the plasma levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), indicating liver toxicity. Collectively, our results showed that methylglyoxal increases cell death and induces liver toxicity, which results from ROS-mediated mitochondrial dysfunction and oxidative stress.

• 대한한의학방제학회지
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• 제32권3호
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• pp.203-221
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• 2024

Objective: Hyangsanondam-tang (⾹⼭溫膽湯, HSODT) is one of the Korean herbal formula for treatment of insomnia, neurosis and anxiety induced by liver Qi stagnation and unhealthy heart. We investigated the hepatoprotective effect of HSODT against arachidonic acid (AA) + iron-mediated cytotoxicity in HepG2 cells. Methods: AA + iron induced oxidative stress and mitochondrial dysfunction in HepG2 cells. The cytoprotective effects of HSODT were determined by MTT assay, western blot and fluorescence activated cell sorting analysis. Results: In HepG2 cells, pretreatment with HSODT significantly suppressed cytotoxicity and the expression of proteins related to apoptosis induced by AA + iron. In addition, pretreatment with HSODT significantly prevented the increase of H₂O₂ production, and decrease GSH depletion and mitochondrial membrane potential induced by AA + iron. Conclusions : These results indicated that HSODT could protect against oxidative stress-induced liver damage.

• 동의생리병리학회지
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• 제30권1호
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• pp.20-26
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• 2016

Prunellae Spica, the herbaceous plant in the genus Prunella, is a traditional herbal medicine and has been reported to have diuretic, anti-bacterial and anti-oxidant effects. However, the mechanism of its action was not clearly identified. In the present study, we investigated the hepatoprotective effect of Prunellae Spica extract (PSE) against the damage of mitochondria and death in hepatocyte induced by oxidative stress. Treatment of arachidonic acid (AA)+iron significantly induced oxidative stress and apoptosis in the hepatocytes. However, PSE protected cells and inhibited apoptosis by altering the protein levels such as poly(ADP-ribose) polymerase and pro-caspase 3. Moreover, AA+iron induced reactive oxygen species production and mitochondrial dysfunction, and Both of them were inhibited by PSE treatment. PSE markedly activated AMP-activated protein kinase (AMPK), an important regulator in cell survival. Furthermore, this activation by PSE was mediated with liver kinase B1, a major upstream kinase that phosphorylates Thr 172 of AMPKα, and this activation was associated with its cell protection, as assessed by an experiment of a chemical inhibitor. In conclusion, this study demonstrate that PSE protects hepatocytes against oxidative stress as mediated with activation of LKB1-dependent AMPK pathway.

• Nutrition Research and Practice
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• 제10권4호
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• pp.386-392
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• 2016

BACKGROUND/OBJECTIVES: Changes in nutritional status during gestation and lactation have detrimental effects on offspring metabolism. Several animal studies have shown that maternal high-fat diet (HFD) can predispose the offspring to development of obesity and metabolic diseases, however the mechanisms underlying these transgenerational effects are poorly understood. Therefore, we examined the effect of maternal HFD consumption on metabolic phenotype and hepatic expression of involved genes in dams to determine whether any of these parameters were associated with the metabolic outcomes in the offspring. MATERIALS/METHODS: Female C57BL/6 mice were fed a low-fat diet (LFD: 10% calories from fat) or a high-fat diet (HFD: 45% calories from fat) for three weeks before mating, and during pregnancy and lactation. Dams and their male offspring were studied at weaning. RESULTS: Dams fed an HFD had significantly higher body and adipose tissue weights and higher serum triglyceride and cholesterol levels than dams fed an LFD. Hepatic lipid levels and mRNA levels of genes involved in lipid metabolism, including $LXR{\alpha}$, SREBP-2, FXR, LDLR, and ABCG8 were significantly changed by maternal HFD intake. Significantly lower total liver DNA and protein contents were observed in dams fed an HFD, implicating the disturbed liver adaptation in the pregnancy-related metabolic demand. HFD feeding also induced significant oxidative stress in serum and liver of dams. Offspring of dams fed an HFD had significantly higher serum cholesterol levels, which were negatively correlated with liver weights of dams and positively correlated with hepatic lipid peroxide levels in dams. CONCLUSIONS: Maternal HFD consumption induced metabolic dysfunction, including altered liver growth and oxidative stress in dams, which may contribute to the disturbed cholesterol homeostasis in the early life of male mice offspring.

• 대한한의학방제학회지
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• 제24권3호
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• pp.163-174
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• 2016

Objectives : Rheum undulatum Linne and Glycyrriza uralensis Fischer are widely used herbal medicine. In this study, anti-oxidant and liver protective effects of R. undunlatum extract (RUE) and G. uralensis extract (GUE) were investigated in HepG2 cells, respectively. Oxidative stress and liver fibrosis were induced by arachidonic acid (AA) and iron, and CCl₄.Methods : MTT assay was assessed for cell viability, and immunoblotting analysis was performed to detect expression of apoptosis related proteins. In addition, reactive oxygen species (ROS) and mitochondrial dysfunction were measured. In vivo, BALB/c mouse were orally administrated with the aqueous extract of 10 mg/kg RUE and 100 mg/kg GUE for 3 days and then, injected with CCl₄ 0.5 ml/kg body weight to induce acute liver damage. Serum ALT level was measured, and histological change was observed in Harris's hematoxylin and eosin stainResults : RUE and GUE pre-treatment increased relative cell viability in concentration dependent manner and altered the expression levels of apoptosis-related proteins such as procaspase 3, PARP and Bcl-xL. RUE and GUE also inhibited the mitochondrial dysfunction and excessive reactive oxygen species (ROS) production induced by AA and iron. In addition, RUE and GUE activated liver kinase B1 (LKB1), by increasing phosphorylation. Moreover, RUE and GUE treatment decreased liver injuries induced by CCl₄, as evidenced by decreases in histological liver damage as well as serum alanine amino transferase (ALT) level.Conclusions : These data suggest that RUE and GUE has anti-oxidant and liver protective effects against AA and iron-induced oxidative stress and CCl₄-induced liver injury.

• 한국식품영양과학회지
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• 제35권10호
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• pp.1329-1335
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• 2006

AIDS로의 진행과정은 단순히 몇몇 기작에 의한 것이 아니라 여러 경로를 거쳐 발생하며 그 진행속도도 개개인에 따라 다양하게 나타나고 있다. 본 연구에서는 쥐 AIDS 모델을 이용하여 항산화호르몬으로 알려진 DHEAS의 면역조절 효과를 확인하고자 하였다. DHEAS의 투여는 LP-BM5 retrovirus 감염으로 인한 T와 B 임파구의 mitogenesis를 증가시켰으며 Th1/Th2 type cytokines의 발현에도 영향을 미쳤는데 주로 전사수준에서 작용한 것으로 생각된다/ 또한 retrovirus 감염으로 인한 간조직의 지질과산화 유발을 억제하여 조직 내의 항산화제인 vitamin E의 함량을 유지시킴으로 NF-kB의 활성화를 통한 retrovirus의 복제를 억제시켜 Th1/Th2 type cytokines의 불균형적인 발현을 저해하였을 것으로 여겨진다. 따라서 쥐 AIDS모델에 있어서 DHEAS의 면역조절 효과를 확인한 본 연구는 향후 HIV감염 이후 AIDS로의 진행 과정 시 항산화제의 역할과 기작 규명에 대한 가능성을 제시할 수 있을 것으로 생각된다.

• 대한한의학방제학회지
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• 제31권4호
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• pp.265-281
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• 2023

Objectives : Ukgan-san plus Citri Pericarpium and Pinelliae Rhizoma (UCP) is used as a traditional herbal formula in Korea and Japan for treatment of fever, fever-induced convulsions, and liver dysfunction and so on. In this study, we investigated the cytoprotective effect and underlying mechanism of UCP against oxidative stress induced by cotreatment of arachidonic acid (AA) and iron. Methods : To evaluate the hepatoprotective effects of UCP against AA + iron-induced oxidative stress in HepG2 cell, cell viability and changes on apoptosis-related proteins were assessed by MTT and immunoblot analyses. The changes in intracellular reactive oxygen species (ROS), glutathione (GSH), and mitochondrial membrane permeability (MMP) were investigated against to the oxidative stress. Furthermore, to verify underlying molecular mechanism, NF-E2-related factor 2 (Nrf2) and its downstream target genes were examined by immunoblot analysis. Results : Treatment of UCP increased the cell viability and altered the expression levels of apoptosis-related proteins such as PARP, caspase-9, caspase-3, Bcl-2. UCP also inhibited the GSH depletion, excessive ROS production and mitochondrial dysfunction induced by AA + iron. In addition, the Nrf2 and the Nrf2 target genes activation were increased by UCP. Conclusions : These results indicated that UCP has the ability to protect against oxidative stress-induced hepatocyte damage, which may be mediated with Nrf2 pathway.

• Biomolecules & Therapeutics
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• 제27권2호
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• pp.222-230
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• 2019

Intestinal barrier dysfunction always accompanies cirrhosis in patients with advanced liver disease and is an important contributor facilitating bacterial translocation (BT), which has been involved in the pathogenesis of cirrhosis and its complications. Several studies have demonstrated the protective effect of Vitamin D on intestinal barrier function. However, severe cholestasis leads to vitamin D depletion. This study was designed to test whether vitamin D therapy improves intestinal dysfunction in cirrhosis. Rats were subcutaneously injected with 50% sterile $CCl_4$ (a mixture of pure $CCl_4$ and olive oil, 0.3 mL/100 g) twice a week for 6 weeks. Next, $1,25(OH)_2D_3$ ($0.5{\mu}g/100g$) and the vehicle were administered simultaneously with $CCl_4$ to compare the extent of intestinal histologic damage, tight junction protein expression, intestinal barrier function, BT, intestinal proliferation, apoptosis, and enterocyte turnover. Intestinal heme oxygenase-1 (HO-1) expression and oxidative stress were also assessed. We found that vitamin D could maintain intestinal epithelial proliferation and turnover, inhibit intestinal epithelial apoptosis, alleviate structural damage, and prevent BT and intestinal barrier dysfunction. These were achieved partly through restoration of HO-1 and inhibition of oxidative stress. Taken together, our results suggest that vitamin D ameliorated intestinal epithelial turnover and improved the integrity and function of intestinal barrier in $CCl_4$-induced liver cirrhotic rats. HO-1 signaling activation was involved in these above beneficial effects.