• 대한한의학방제학회지
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• 제11권2호
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• pp.135-146
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• 2003

Objectives : Wolguk-whan has been used as a prescription of natural drug for the treatment of stress digestive system disease. Recently, we reported that Wolguk-whan methnol extract (WGWM) exerted a significant protective effect against oxidative damage to the liver of ICR mice. This study was purposed to investigate the effects of Wolguk-whan water extract (WGWW) on liver injury induced by oxidative stress. Methods : In order to investigate the effects of WGWW on acute liver injury, ICR mice were pretreated with WGWW for 6days, starved for 24hrs, and administerated acetamirtophen(500mg/kg, i.p.). In the liver homogenates, lipid peroxide and glutathione(GSH) levels were measured. In addition, activities of hepatic enzyme, such as catalase, glutathione peroxidase(GSH-Px), glutathione S-transferase(GST) were measured in the hepatic mitochondrial and cytosolic fractions. Results : In vivo administeration of WGWW showed effective inhibition of acetaminophen induced lipid peroxidation, and showed elevations of GSH level, catalase, GSH-Px, GST activities. Conclusions : These results suggested that WGWW might suppress the formation of oxidative metabolites, and prevent acetaminophen induced hepatotoxicity.

• 한국전자현미경학회:학술대회논문집
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• 한국현미경학회 1994년도 제25회 학술대회 연제 초록
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• pp.21-21
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• 1994

• Korean Journal of Acupuncture
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• 제20권4호
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• pp.41-52
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• 2003

Objectives : Circii Herba has been used as a natural drug for the treatment of stress digestive system disease. The aim of this study is to investigate the role of Circii Herba aqua-acupuncture solution (CHAS) in experimental oxidative liver injury. Methods : In order to investigate the effects of CHAS on acute liver injury, male ICR mice were pretreated with CHAS(0.2 ml/mouse/day) at the loci of BL18 and CV12 for 6days, starved for 24hrs, and administerated acetaminophen(500 mg/kg, i.p.). After acetaminophen administeration, mice were sacrificed, and the liver was removed, rinsed with ice-cold $1.15{\%}$ KCI buffer, and homogenized at $4^{\circ}C$. Fractions(fraction Ⅰ, Ⅱ, Ⅲ) were isolated by differential centrifugation. Lipidperoxide, total SH, and glutathione(GSH) levels were measured in the Fraction Ⅰ. In addition, activities of hepatic enzyme, such as catalase, glutathione peroxidase(GSH-Px) were measured in the Fraction Ⅱ, and glutathione S-transferase(GST) was measured in the Fraction Ⅲ. Results : In vivo treatment of CHAS(BL18 and CV12) showed effective inhibition of acetaminophen induced lipid peroxidation, and showed elevations of total SH, GSH level, catalase, GSH-Px, GST activities. Conclusions : These results suggested that CHAS might suppress the formation of oxidative metabolites, and prevent acetaminophen induced hepatotoxicity.

• 대한한의학방제학회지
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• 제16권2호
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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.

• 한국식품위생안전성학회지
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• 제13권3호
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• pp.258-267
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• 1998

해혈 및 진동 효과를 가진 APAP는 과량 복용시 CYP-450에 의해 독성 유발 물질인 NAPQI로 대사되어 간장과 세포막을 붕괴시켜 세포 내 calcium 유입을 증가시킴으로서 간세포의 괴사를 일으킨다. DIL은 CYP-450 작용을 억제하는 것으로 알려진 칼슘채널차단제이다. 따라서 본 연구에서는 APAP 300mg/kg을 경구 투여한 후 3, 6. 9 및 12시간에 DIL을 복상내로 투여하여 DIL이 APAP의 독성에 미치는 영향을 조사하였다. APAP 투여 12시간후 DIL 투여군에서 혈청과 간조직의 생화학 분석과 조직학적 관찰에서 간손상의 개선 효과가 확인되었으며, 이는 세포내로의 calcium 유입과 지질과산화의 억제 및 GST의 활성도 증가에 기인한 것으로 보인다. 그러므로 APAP 과량 복용 12시간 후의 DIL 투여는 간손상의 억제에 효과적일 것으로 사료된다.

• 한국환경독성학회:학술대회논문집
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• 한국환경독성학회 1996년도 제19회정기학술대회(The 19th Symposium of the Korean Society of Environmental Toxicology)
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• pp.54-54
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• 1996

• BMB Reports
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• 제52권3호
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• pp.190-195
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• 2019

Acetaminophen (APAP) overdose can cause hepatotoxicity by inducing mitochondrial damage and subsequent necrosis in hepatocytes. Sirtuin2 (Sirt2) is an $NAD^+$-dependent deacetylase that regulates several biological processes, including hepatic gluconeogenesis, as well as inflammatory pathways. We show that APAP decreases the expression of Sirt2. Moreover, the ablation of Sirt2 attenuates APAP-induced liver injuries, such as oxidative stress and mitochondrial damage in hepatocytes. We found that Sirt2 deficiency alleviates the APAP-mediated endoplasmic reticulum (ER) stress and phosphorylation of the p70 ribosomal S6 kinase 1 (S6K1). Moreover, Sirt2 interacts with and deacetylates S6K1, followed by S6K1 phosphorylation induction. This study elucidates the molecular mechanisms underlying the protective role of Sirt2 inactivation in APAP-induced liver injuries.

• 한국식품과학회지
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• 제39권6호
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• pp.688-693
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• 2007

아세트아미노펜(APAP)으로 유도된 간독성 모델에 미치는 잔대를 주재료로 하는 추출물(ATJH)의 간보호 효능을 관찰하기 위하여 동물모델에서 혈청 간기능 지표효소의 활성도를 측정하고 조직학적인 변화를 관찰하였다. APAP를 투여한 동물군은 ALT와 AST활성을 현저하게 증가시켰다. ATJH를 1000 mg/kg의 용량으로 3일간 전투여한 후 APAP로 간 독성을 유도한 동물은 증가된 AST, ALT활성을 약 60-80% 감소시켰으며, 500 mg/kg의 용량으로 장기간(7일간) 전투여한 동물에서도 APAP독성방어효과가 현저하였다. APAP를 고농도(450 mg/kg)로 투여하여 간손상에 의한 사망을 유도한 동물군에서 ATJH는 생존율을 대조군에 비하여 130% 증가시켰다. APAP 단독 투여한 군에서 80-90% 정도 간세포 괴사가 관찰되었으나 ATJH(500, 1000 mg/kg)를 3일간 전투여 한 군에서는 간조직 손상이 억제되었다. 동물모델에서 ATJH에 의한 간독성 방어효능의 기전을 연구하기 위하여 간세포에서 제2상 해독화 효소인 GST의 단백 발현 변화를 면역화학적으로 관찰하였다. ATJH는 농도의존적으로 GSTA2, GSTA3/5의 단백 발현을 유의성있게 유도하였다. 본 연구에서는 잔대를 주원료로 한 추출물이 간세포의 해독화효소의 발현을 증가시킴으로서 APAP에 의해 유발된 간손상을 억제함을 처음으로 증명하였고, 간조직 보호를 위한 화학적 예방 효능을 갖는 활성물질로서 ATJH의 가능성을 제시한다.

• Biomolecules & Therapeutics
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• 제17권4호
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• pp.455-460
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• 2009

Foods of plant origin, especially fruits and vegetables, have attracted attention because of their potential benefits to human health. In this report, Rubi Fructus (RF), the dried unripe fruit of Rubus coreanus Miq (Rosaceae) and ellagic acid (EA) purified from RF were used to test their potential hepatoprotective effect against acetaminophen (AAP)-induced hepatotoxicity in rats. RF extract (RFext) and EA reduced the elevated levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) in serum and the content of lipid peroxide in liver by AAP administration, while the increment of the cellular glutathione (GSH) content and the induction of glutathione S-transferase (GST) and glutathione peroxidase (GSH-PX) which were decreased by AAP administration. RFext and EA from RFext did not affect the two major form of cytochrome P450s, cytochrome P450 2E1 (CYP2E1) and cytochrome P450 1A2 (CYP1A2), but downregulated the cytochrome P450 3A4 (CYP3A4) related to the conversion of AAP to N-acetyl-P-benzoquinone imine (NAPQI). These results suggest that RFext and EA from RF exhibit a hepatoprotective effect not only by increasing antioxidant activities but also by down-regulating CYP3A4 in the AAP-intoxicated rat.

• 동의생리병리학회지
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• 제16권4호
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• pp.707-713
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• 2002

Astragali radix (AR) is one of the oldest and mast frequently used crude drug for traditional medicine in many Asian countries. This study designed to investigate the hepatoprotective effects of the aqueous extracted AR (ARE) against acetaminophen (APAP)-induced hepatic damage in ICR mice. APAP at the dose of 450 mg/kg i.p produced liver damage in ICR mice. Serum enzyme activities of alanine aminotransferase, aspartate aminotransferase and sorbitol dehydrogenese was dramatically decreased up to control level by pretreatment of ARE. However, hepatic glutathione level did not show a significant change between the tested groups. We also investigated TNF α mRNA gene expression on APAP-induced liver damage by RT-PCR. APAP dramatically induced TNF α mRNA gene expression in ICR mice. Pretreatment of mice with ARE led to a marked decrease of TNF α mRNA gene expression. These data indicate that 1) ARE has clearly revealed a hepatoprotective effect against APAP-induced hepatic damage in ICR mice, and 2) the protective effect of ARE may be, in part, associated with the regulation of TNF α mRNA gene expression.