• Journal of Sericultural and Entomological Science
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• v.50 no.2
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• pp.93-100
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• 2012

To investigate the effects of Protaetia. brevitarsis extracts on the protection against liver damage by carbon tetrachloride($CCl_4$) in rat, two kinds of experiment were performed, firstly by the primary hepatocyte culture and secondly by the animal feeding. The primary hepatocyte culture with the extracts of P.brevitarsis showed significantly low activities of GPT, bile acid, and bilirubin, indicating an excellent protective effect against liver damage by $CCl_4$. Especially, below molecular weight 1,000 blew the water to have 32.1% recovery degree. In the seconde experiment, serum GPT activity was significantly decreased in water fraction of P. brevitarsis compared to $CCl_4$ treatment by 98.2%. Serum concentration of bile acid and bilirubin were tended to increased by $CCl_4$ treatment, but water fraction of P. brevitarsis and silymarin recovered the level. These consistent results in vitro and in vivo suggest that the extracts of P. brevitarsis may have strong protective effects against liver damage induced by the potential toxicants such as $CCl_4$.

• Korean Journal of Acupuncture
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• v.23 no.2
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• pp.167-176
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• 2006

목 적 : 본 연구는 태충(太衝) 및 양지혈(陽池穴) 에 대한 전침(電鍼)이 galactosamine 을 이용한 백서의 간독성(肝毒性)을 실험적으로 유발시킨 모델에서 예방효과(豫防效果)를 알아보고자 혈청중의 $\gamma\;-GTP$, GOT, GPT, LDH, total bilirubin, total cholesterol, triglyceride 의 변화를 관찰하였다. 방 법 : 간독성은 각 군들은 간독성을 유발하지 않고 무처치한 정상군, 간독성을 유발하고 난 후 무처치한 대조군, 각각 10 Hz, 50 Hz, 100 Hz 전침을 20 일간 10 회 시행한 후 간독성을 유발한 Pre 10, Pre 50, Pre 100군 등으로 분류하였다. 결 과 : 태충(太衝) 양지혈(陽池穴)에 대한 전침(電鍼) 치료(治療)의 예방효과(豫防效果)에서는 Pre 10 군에서는 ${\gamma}\;-GTP$, GOT, GPT, total cholesterol, triglyceride이 Pre 50군에서는 ${\gamma}\;-GTP$GOT, GPT, LDH, total bilirubin, total cholesterol이, Pre 100 군에서는 ${\gamma}\;-GTP$, GOT, LDH, total bilirubin, total cholesterol이 대조군에 비해 감소하였다. 결 론 : 위의 결과를 종합해보면 간독성에 대하여 태충(太衝) 양지혈(陽池穴)의 전침(電鍼)을 시행한 모든 군에서 간능과 지절대사에서 간손상에 대한 유의한 예방효과를 나타내었다.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1993.04a
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• pp.172-172
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• 1993

Acetaminophen(이하 AAP)은 간의 mixed function oxidase system에 의해 toxic metabolite로 대사되어 간괴사를 일으킨다. 최근에는 지금까지 임상적으로 사용되어온 한약이나 생약의 cytochrome P450의 활성과 간의 glutathion 합성에 미치는 영향에 대한 연구가 활발하게 진행되고 있다. 본 연구에서는 AAP의 간독성을 억제하는 물질을 규명하고자 민간이나 한방에서 보간 또는 해독제로 많이 사용되고 있는 생약을 screening하였다. 그 결과 간의 약물대사 효소계에 엉힝을 미치는 것으로 보고된 강활(Angelica koreana)과 민간이나 한방에서 간질환치료의 목적이나 해독제로 쓰여온 시호(Buplerum falcatum), 토복령(Smilax china) 및 금은화(Lonicera japonica)가 AAP로 유발된 간독성에 미치는 효과를 살펴보았다. 방법: 예비실험을 통해 강활, 시호, 토복령 및 금은화의 MeOH ext.가 AAP로 유도된 간독성에 방어효과가 있음을 확인하고 이를 hexane, ether, ethyl acetate 및 butanol로 계통분획하여 랫트에 전처치한 후 고농도의 AAP를 투여하여 간 손상을 일으키고 혈청중의 효소활성과 지질ㆍcholesterolㆍbilirubin함량 등을 측정하였다.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1993.04a
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• pp.97-97
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• 1993

본 연구과제에서는 적출판류간실험법 (isolated perfused liver technique)을 약물의 간독성 유발 및 보간작용에 관한 실험법으로 개발하고자 butylated hydroxyanisole (BHA) 을 이용하여 보간실험을 하였다. BHA를 식이투여한 흰쥐로부터 적출한 간에 간독성 모델물질로 2,6-dichlorophenolindophenol (DCPIP) 을 관류시켜 관류액내의 DCPIP의 유리형, 환원형, glucuronide, sulfate 포합체의 대사체를 측정하여 DCPIP 외 대사양상을 관찰하였으며, 동시에 간세포 손상으로 관류액내로 유출된 lactate dehydrogenase (LDH)의 활성도를 측정하여 DCPIP예 의할 간세포독성 유발정도를 간접적으로 측정하여 대조군과 비교하였다. 그리고 BHA에 의한 보간작용이 약물대사효소의 변와에 기인한 것인가를 관찰하기 위하여 모델약물로 7-ethoxycoumarin (EC) 이나 EC의 phase I 대사산물인 7-hydroxycoumarin (HC) 을 관류시켜 관류액내의 HC의 유리체, glucuronide 포합체, sulfate 포합체로의 대사량을 측정하여 약물대사시 약물의 활성화에 관계하는 phase I mixed function oxidase (MFO) 효소와 약물의 해독화에 관계하는 phase II 포합효소 (UDP-glucuronyltranesferase(UDPGT)와 sulfotransferase (ST))의 활성도 변화를 측정하여 대조군과 비교하였다. 간독성 모델물질인 DCPIP를 적출한 흰쥐의 간에 관규시켰을때 BHA 전처리군이 LDH가 유출되기 시작하는 시간이 대조군에 비하여 유의적으로 늦었으며, LCH가 유출량도 유의적으로 감소되어 DCPIP에 의한 간독성 유발능력이 BHA에 의하여 감소됨을 관찰하였다. 아울러 DCPIP의 대사체중 환원체와 glucuronide 포합체의 생성량이 증가되어 BHA에 의하여 quinone reductase와 UDPGT 활성도가 증가되었음을 알 수 있었다. 그리고 BHA 전처리에 의하여 MFO효소계와 ST의 활성도에는 변화가 없었으나 UDOGT 의 활성도는 약 2.2배 증가되었다. 이상의 결과로 BHA에 의한 보간작용은 간독성 물질을 활성화시키는 phase I MFO 효소의 활성도에는 변화없이 해독작용에 관여하는 phase II효소들의 활성도 증가에 기인된 것을 알 수 있었다. 그리고 이러한 결과는 적출한 관류간실험법은 여러 약물의 보간효과를 관찰하는 실험법으로 적합할 것으로 사료되었다.

• The Journal of Korean Medicine
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• v.15 no.2 s.28
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• pp.253-268
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• 1994

오종(五種) 약침액(藥鍼液)(약침액(藥鍼液)의 명칭(名稱) : V. OK. I. HO. B)의 안전성(安全性)을 실험적(實驗的)으로 검토(檢討)하기 위하여 급성독성여부(急性毒性與否)를 연구보고(硏究報告)한 이후 발열성시험(發熱性試驗), 피부자극시험(皮膚刺戟試驗), 용혈반응(溶血反應) 및 간독성(肝毒性)과 신독성시험(腎毒性試驗)을 실시(實施)하여 유의(有意)한 결과(結果)를 얻었다. 모든 약침액(藥鍼液)은 발열성시험(發熱性試驗)과 피부자극시험(皮膚刺戟試驗), 간독성(肝毒性) 및 신독성시험상(腎毒性試驗上) 이상소견(異常所見)이 발견(發見)되지 않았으나 용혈반응(溶血反應)의 경우 일부(一部) 약침액(藥鍼液)에서 용혈반응(溶血反應)을 의심(疑心)할 수 있으므로 향후(向後) 이에 대(對)한 연구(硏究)와 세포독성(細胞毒性) 및 항원성시험(抗原性試驗)이 필요(必要) 할 것으로 사려(思慮)된다.

• Korean Journal of Microbiology
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• v.45 no.4
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• pp.416-418
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• 2009

The hepatoprotective effect of Cordyceps militaris culture broth was determined using HaM/ICR strain mice. Compared to control, the intra-peritoneal injection of benzo($\alpha$)pyrene (B($\alpha$)P) remarkably increased the activities of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in the serum and the level of lipid peroxide (LPO) in liver tissue, which mean the liver was damaged by B($\alpha$)P. However, compared to B($\alpha$)P, oral administration of C. militaris culture broth showed decrement of AST, ALT, and LPO activities and increment GST activity and GSH level in liver tissue. These suggest that C. militaris culture broth recovered hepatic damage induced by B($\alpha$)P.

• Korean Journal of Food Science and Technology
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• v.53 no.3
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• pp.344-347
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• 2021

In this study, the hepatotoxic mechanism of chaparral (Larrea tridentata) was investigated through in vitro experiments that measured cell death, inflammatory cytokine secretion, and intracellular fat accumulation by treating HepG2 hepatocytes with a 70% ethanol extract of chaparral at concentrations ranging from 0.001 to 100 ㎍/mL. Cell death was observed after treatment with chaparral extract at concentrations of 1-100 ㎍/mL (p<0.05). The secretion of the inflammatory cytokines, interleukin-8 and macrophage-colony stimulating factor, and fat accumulation were significantly increased even at a concentration of 0.1 ㎍/mL, which was 10 times lower than the observed concentration resulting in cell death (p<0.05). Hepatitis caused by inflammatory cytokine secretion and fat accumulation was shown to be a form of hepatotoxicity induced by chaparral extract. Hepatitis was expressed at a concentration lower than that causing serious toxicity such as cell death, suggesting that hepatotoxicity, including hepatitis, may be caused by ingestion of low concentrations of chaparral.

• Journal of the Korean Society of Food Science and Nutrition
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• v.22 no.2
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• pp.144-148
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• 1993

The present study was undertaken to compare the pharmacological activities of crude Lithospermi radix reported with the clinical uses in the oriental medicine. Crude Lithospermi radix uesd for the treatment of burn, eczema, blister, diuretic, scarlet fever and septicemia as antipyretic, antidotic and antiphlogistics. Therefore we tested the effects of Lithospermi radix water extract on the liver-protective activities in the rats. The results obtained from enzyme assay, measurement of serum and liver alanine. aspartate aminotransferase(ALT, AST) and lipid composition indicated that Lithospermi radix water extract showed significant liver-protective activities against benzo(a)pyrene-induced hepatotoxicity.

• The Korean Journal of Pharmacology
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• v.32 no.3
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• pp.407-416
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• 1996

The reactive intermediates formed during the metabolism of therapeutic agents, toxicants and carcinogens by cytochromes P450 are frequently capable of covalently binding to tissue macromolecules and causing tissue damage. It has been shown that YH439, a congener of malotilate, is effective in suppressing hepatic P450 2E1 expression. The present study was designed to further establish the mechanistic basis of YH439 protection against toxicant by assessing its effects against chemical-mediated potentiated hepatotoxicity. Retinoyl palmitate (Vit-A) pretreatment of rats for 7 days substantially enhanced carbon tetrachloride hepatotoxicity, as supported by an ${\sim}5-fold$ increase in serum alanine aminotransferase (ALT) activity, as compared to $CCl_4$ treatment alone. The elevation of ALT activity due to Vit-A was completely blocked by the treatment of $GdCl_3$ a selective inhibitor of Kupffer cell activity. Concomitant pretreatment of rats with both YH439 and Vit-A resulted in a 94% decrease in Vit-A-potentiated $CCl_4$ hepatotoxicity. YH439 was also effective against propyl sulfide-potentiated $CCl_4-induced$ hepatotoxicity. Whereas propyl sulfide (50 mg/kg, 7d) enhanced $CCl_4-induced$ hepatotoxicity by >5-fold, relative to $CCl_4$ treatment alone, concomitant treatment of animals with both propyl sulfide and YH439 at the doses of 100 and 200 mg/kg prevented propyl sulfide-potentiated $CCl_4$ hepatotoxicity by 35% and 90%, respectively. Allyl sulfide, a suppressant of hepatic P450 2E1 expression, completely blocked the propyl sulfide-enhanced hepatotoxicity, indicating that propyl sulfide potentiation of $CCl_4$ hepatotoxicity was highly associated with the expression of P450 2E1 and that YH439 blocked the propyl sulfide-enhanced hepatotoxicity through modulation of P450 2E1 levels. Propyl sulfide- and $CCl_4-induced$ stimulation of lipid peroxidation was also suppressed by YH439 in a dose-related manner, as supported by decreases in malonedialdehyde production. The role of P450 2E1 induction in the potentiation of $CCl_4$ toxicity and the effects of YH439 were further evaluated using pyridine as a P450 2E1 inducer. Pyridine pretreatment substantially enhanced the $CCl_4$ hepatotoicity by 23-fold, relative to $CCl_4$ alone. YH439, however, failed to reduce the pyridine-potentiated toxicity, suggesting that the other form(s) of cytochroms P450 inducible by pyridine, but not suppressible by YH439 treatment, may play a role in potentiating $CCl_4-induced$ hepatotoxicity. YH439 was capable of blocking cadmium chloride-induced liver toxicity in mice. These results demonstrated that YH439 efficiently blocks Vit-A-enhanced hepatotoxiciy through Kupffer cell inactivation and that the suppression of P450 2E1 expression by YH439 is highly associated with blocking of propyl sulfide-mediated hepatotoxicity.

• Journal of Food Hygiene and Safety
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• v.26 no.3
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• pp.235-241
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• 2011

Although the vegetable Angelica keiskei (AK) has widely been utilized for the purpose of general health improvement among Korean population, its functionalities are not very well defined. In this study, we examined the effects of methanol extract of AK in rats on the biochemical changes induced by two hepatotoxins, D-galactosamine (GalN) and carbon tetrachloride ($CCl_4$). AK was orally administered once daily for 7 days to male rats at 200 and 500 mg/kg, before hepatotoxins. Effects of AK were assessed 24 hr later. AK pretreatments at 200 and 500 mg/kg significantly blunted GalN-induced elevation in liver lipid peroxidation, plasma aspartate-transaminase (AST) and alanine-transaminase (ALT) activities. AK also prevented, after 500 mg/kg but not after 200 mg/kg, the GalN-induced elevation in triglyceride, total cholesterol and LDL-cholesterol levels. Differently from against GalN-induced toxicity, AK did further elevate the $CCl_4$-induced rise in AST, ALT and lipid peroxidation. These results suggest that AK, when pre-administered prior to GalN, exerted protective effects against GalN-induced hepatotoxicity, in contrast however, AK exacerbated that induced by $CCl_4$. To explore possible mechanism for the toxicity-potentiating effects of AK on $CCl_4$, the activity of hepatic drug metabolism after AK treatment was assessed. It was observed that AK increased the activity of aniline hydroxaylase, a cytochrome P450 isoenzyme responsible for metabolic activation of $CCl_4$. This finding suggests that hepatoprotective effects of AK are not equally expected depending on hepatotoxins employed.