• Archives of Pharmacal Research
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• 제23권6호
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• pp.620-625
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• 2000

The mechanisms of liver injury from cold storage and reperfusion are not completely under-stood. The aim of the present study was to investigate whether the inactivation of Kupffer cells (KCs) by gadolinium chloride ($GdCl_3$) modulates ischemia-reperfusion injury in the rat liver. Hepatic function was assessed using an isolated perfused rat liver model. In livers subjected to cold storage at $4^{\circ}C$ in University of Wisconsin solution for 24 hrs and to 20 min rewarm-ing ischemia, oxygen uptake was markedly decreased, Kupffer cell phagocytosis was stimulated, releases of purine nucleoside phosphorylase and lactate dehydrogenase were increased as compared with control livers. Pretreatment of rats with $GdCl_3$) , a selective KC toxicant, suppressed kupffer cell activity, and reduced the grade of hepatic injury induced by ischemia-reperfusion. While the initial mixed function oxidation of 7-ethoxycoumarin was not different from that found in the control livers, the subsequent conjugation of its meta-bolite to sulfate and glucuronide esters was suppressed by ischemia-reperfusion, CdCl$_3$restored sulfation and glucuronidation capacities to the level of the control liver. Our findings suggest that Kupffer cells could play an important role in cold/warm ischemia-reperfusion hepatic injury.

• 약학회지
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• 제42권6호
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• pp.598-606
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• 1998

The liver expresses a considerable amount of nitric oxide (NO) upon induction with cytokines or/and endotoxin. The NO synthesized by inducible NO synthase (NOS) of the liver see ms to play a role in various hepatic physiological processes. Here we investigate the effects of NO on acetaminophen (AA)-induced liver injury. The treatment of S-nitros-N-acetyl penicillamine (SNAP, exogenous NO donor) at the dose of 0.1mM decreased AA-induced hepatotoxicity suggesting the possibility of NO to play a role in protection from the hepatotoxicity induced by AA. On the other hand, the excessive NO produced by NO donor (SNAP: 0.5, 2.5, 6.25mM) has been shown to cause a concentration dependent hepatotoxicity, and such damages was decreased by Superoxide and increased by superoxide dismutase, indicating that the hepatotoxicity induced by excessive NO depends on balancing between NO and superoxide. Taken together, the results indicate that NO has biphasic effects on hepatotoxicity.

• 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.

• Environmental Analysis Health and Toxicology
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• 제8권1_2호
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• pp.31-35
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• 1993

The present study was undertaken to find a protective effect of Coptis Rhizoma Extract on liver injury induced by benzo(a)pyrene in rats. This crude drug significantly suppressed the increase of several biochemical parameters such as transaminase, lactate dehydrogenase and alkaline phosphatase in serum and liver and total cholesterol. But there were little changes in elevated serum phospholipid level. The results suggested that Coptis Rhizoma prevent bezo(a)pyrene-induced hepatic injury.

• Asian Pacific Journal of Cancer Prevention
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• 제15권23호
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• pp.10413-10420
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• 2015

Side effects are an unavoidable consequence of chemotherapy drugs, during which liver injury often takes place. The current study was designed to investigate the protective effect of Astragalus polysaccharides (APS) against the hepatotoxicity induced by frequently-used chemical therapy agents, cyclophosphamide (CTX), docetaxel (DTX) and epirubicin (EPI)) in mice. Mice were divided into five groups, controls, low or high dose groups ($DTX_L$, $CTX_L$, $EPI_L$ or $DTX_H$, $CTX_H$, $EPI_H$), and low or high dose chemotherapeutics+APS groups ($DTX_L$+APS, $CTX_L$+APS, $EPI_L$+APS or $DTX_H$+APS, $CTX_H$+APS, $EPI_H$+APS). Controls were treated with equivalent normal saline for 28 days every other day; low or high dose group were intraperitoneal (i.p) injected with low or high doses of CTX, DTX and EPI for 28 days every other day; low or high dose chemotherapeutics+APS group were separately intraperitoneal (i.p) injected with chemotherapeutics for 28 days every other day and i.p with APS (100 mg/kg) for 7 days continually from the 22th to the 28th days. The body weight, serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), histopathological features, and ultrastructure morphological change of liver tissues, protein expression level of caspase-3 were estimated at different time points. With high dose treatment of DTX, CTX and EPI, weight gain was inhibited and serum levels of ALT and AST were significantly increased. Sections of liver tissue showed massive hepatotoxicity in $CTX_H$ group compared to the control group, including hepatic lobule disorder, granular and vacuolar degeneration and necrosis in hepatic cells. These changes were confirmed at ultrastructural level, including obvious pyknosis, heterochromatin aggregation, nuclear membrane resolution, and chondrosome crystal decrease. Western blotting revealed that the protein levels of caspase-3 increased in $CTX_H$ group. The low dose groups exhibited trivial hepatotoxicity. More interestingly, after 100 mg/kg APS, liver injury was redecued not only regarding serum transaminase activities (low or high dose chemotherapeutics+APS group), but also from pathological and ultrastructural changes and the protein levels of caspase-3 ($CTX_H$+APS group). In conclusion, DTX, CTX and EPI induce liver damage in a dose dependent manner, whereas APS exerted protective effects.

• 대한한방내과학회지
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• 제44권4호
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• pp.751-756
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• 2023

목적: 본 연구는 임상에서 많은 빈도로 사용되고 있는 향정신성 약물이 간독성을 발생시킬 수 있음을 임상 예를 통해 보여줌으로써, 한의진료현장에서 이에 대한 경각심과 더불어 약인성간손상에 대한 최신 정보를 제공하고자 한다. 방법: 본 임상 예의 논문은 향정신성 약물을 사용한 후 약인성간독성의 의심과 진단 및 약물의 중단 후 증상과 간손상 효소의 개선과정을 자세히 제시하였다. 결과: 평소 혼합결합조직병으로 한방병원에서 수년 동안 침과 뜸 치료 등으로 잘 유지되고 있던 56세의 여성 환자가, 어느날부터 갑자기 심한 피로감과 전신적 불편편함을 호소하였다. 혈액검사를 시행한 결과, 혈청 AST, ALT가 정상 경계의 2.5-배 이상 증가하였고, 촤근 복용한 향정신성약물에 대한 RUCAM score가 9점으로 약인성간손상 진단에 부합하였다. 이 의심 약물들을 중지한 뒤에 주관적 불편함이 빠르게 개선되었으며, 혈청 간손상 효소 수치 또한 2주 안에 정상화되었다. 결론: 본 증례는 향정신성약물로 생길 수 있는 간손상의 전형적인 임상 예로서, 향정신성약물의 일반화된 상황에 비추어 한의원에서 환자의 진료 과정에서 하나의 중요한 고려사항을 암시한다.

• 대한한의학회지
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• 제44권4호
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• pp.163-169
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• 2023

Methods: This study presents a comprehensive case study of an elderly male diagnosed with acute kidney injury (AKI) resulting from severe dehydration, supported by an extended follow-up with laboratory findings. Results: An 83-year-old male patient experienced severe diarrhea overnight, leading to hospitalization due to symptoms of dehydration and hypotension. His laboratory results displayed a typical AKI pattern, including a significant increase in creatinine levels (5.19 mg/dL) and the presence of hyperkalemia and hyponatremia. Following general treatments, including the administration of an herbal drug (Bulhwangeumjeonggi-san), the estimated glomerular filtration rate (eGFR) improved from 10 ml/min (Stage 5) to 34 ml/min (Stage 3) within five days when he was discharged. Although subsequent eGFR tests, conducted one and two months later as an outpatient, revealed an improvement of 42 ml/min, the patient still experienced mild chronic dysfunction as a consequence. Conclusion: This study presents a noteworthy case of acute kidney injury attributed to severe dehydration, emphasizing the importance of medical awareness regarding diarrhea-induced kidney function impairment, especially in the elderly population.

• Preventive Nutrition and Food Science
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• 제13권4호
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• pp.269-275
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• 2008

Dandelion (Taraxacum officinale) has been widely used as an anti-inflammatory agent in oriental medicine. In the current study, we investigated the protective effect, and the possible mechanism, of dandelion extracts against ethanol-induced acute hepatotoxicity in C57BL/6 mice. Dandelion water and ethanol extract was administered at 2 g/kg body weight (BW) once daily for 7 consecutive days, whereas control and ethanol groups received water by gavage. Ethanol (50% ethanol; 6 g/kg BW) was administered 12 hr before sacrificing the mice in order to generate liver injury. Significantly increased serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities as well as liver triglyceride (TG) and cholesterol levels were attenuated by dandelion supplementation. In addition, dandelion extracts not only enhanced alcohol dehydrogenase (ADH) and anti-oxidative enzyme activities, but reduced lipid peroxidation. Cytochrome P450 2E1 (CYP 2E1), one of the critical enzymes xenobiotic metabolism, expression was lower with ethanol treatment but restored by dandelion supplementation. These results were confirmed by improved histopathological changes in fatty liver and hepatic lesions induced by ethanol. In conclusion, dandelion could protect liver against ethanol administration by attenuating of oxidative stress and inflammatory responses.

• 대한본초학회지
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• 제33권1호
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• pp.37-46
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• 2018

Objectives : Liver disease is an inflammatory reaction caused by oxidative stress, viral, alcohol, and drug properties. Inflammatory reaction causes hepatitis and chronic hepatitis is persistent, it progresses to liver fibrogenesis and liver cancer. The aim of this study was to confirm the hepatoprotective effect of Tongyuhwalhyeol-tang(Tongqiaohuoxue Decoction) (TH) and Gamtongyuhawlhyeol-tang(GTH) in TAA-induced liver injury animal model. Methods : The antioxidant activities were evaluated through in vitro experiments, such as 1, 1-diphenyl-2-picrylhydrazyl (DPPH) and 2, 2'-azinobis-3-ethyl-benzothiazoline-6-sulfonic acid (ABTS) radical scavenging assays, total polyphenol and total flavonoid content measurement. To confirm the liver protective effect, induced by Thioacetamide (TAA) for 3 days injection at 200 mg/kg rats. TH and GTH were treated 3 days at 200 mg/kg/day. The changes of reactive oxygen species (ROS), peroxynitrite ($ONOO^-$), alanine aminotransferanse (ALT) and aspartate aminotransferase (AST) in serum were analyzed after experiment. Also, expression of anti-inflammation, anti-oxidant related proteins were investigated by western blot analysis. Results : TH was inhibited the antioxidant activities. In the TAA-induced rat, TH decreased ROS, $ONOO^-$, ALT, AST level in serum. Inflammation related protein expressions increased in TAA-induced rat compared to normal rat. However, TH group inhibited the down expression of these proteins. Also, anti-oxidant related protein expressions increased in TH group compared TAA-induced rat. Conclusion : Therefor, these results suggested that TH provided hepatoprotective effects on the hepatic injury leading to the reduction of inflammatory response. In addition, the effect of TH was superior to that of GTH.

• Environmental Analysis Health and Toxicology
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• 제17권3호
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• pp.261-264
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• 2002

The heartwood of Caeralpinia sappan L. (Leguminosae) has been used to activate blood flow, remove blood stasis, reduce swelling and relieve pain in Korean folk medicine. In this study. the antioxidant effects of this crude drug and its hepatoprotective activity on CCl$_4$-induced liver injury in rats were evaluated. The levels of antioxidant enzymes, superoxide dismutase (SOD) and catalase (CAT) reduced by CCl$_4$treatment, were recovered by this crude drug. It is suggested that Caesalpinia sappan L. have antioxidant effect. The increased levels of glutamic oxaloacetic transaminase (GOT) and glutamic pyruvic transaminase (GPT) by CCl$_4$were also recovered by treatment with this crude drug. These results can be attributed to the agent's antioxidant and membrane - stabilizing actions.