• 제목/요약/키워드: $CCl_4$-induced hepatotoxicity

검색결과 180건 처리시간 0.029초

황련해독탕(黃連解毒湯)의 전투여(前投與)가 $CCL_4$와 ethanol 중독(中毒) 흰쥐의 간장(肝臟) 및 신장(腎臟)에 미치는 조직병리학적(組織病理學的) 연구(硏究) (A Histological Study of the effects of $CCL_4$ and Ethanol on the Liver and Kidneys of Rats after Preadministration of Hwangryunhaedoktang)

  • 윤주현;김승모;임명현;박재현
    • 대한한방내과학회지
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    • 제22권1호
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    • pp.5-11
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    • 2001
  • Object : This study was carried out to examine the effect of Hwangryunhaedoktang on the liver and kidney of rats induced by carbon tetrachloride and ethanol. Methods : The histopathological changes were examined after preadministration of 100 and 200mg/100g Hwangryunhaedoktang. Results : The perivenular ballooning degeneration and infiltration of basophilic inflammatory cells were decreased in the experimental group when compared with the control group. No abnormalities were observed in the kidneys of both groups. But, interstitial nephritis was observed only in the experimental group. Conclusion : This study suggests that Hwangryunhaedoktang may be of benefit to the prevention of hepatotoxicity induced by carbon tetrachloride and ethanol, and it is more effective in high dosages.

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음양곽의 항산화작용에 의한 간 보호 효과 (The Hepatoprotective Effects of Epimedii Herba through the Antioxidation)

  • 하배진;김희진;이상헌;하종명;이상현;이재화;이동근;박은경;남천석
    • 생명과학회지
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    • 제15권4호
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    • pp.572-577
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    • 2005
  • 음양곽의 항산화 효과를 규명하기 위하여 흰쥐(Sprague-Dawley계)를 사용하여 음양곽 추출물을 2주간 복강내로 투여하고 $CCl_4$에 의한 간독성 경감기전을 혈액 및 간 조직에서의 효소 변동과 간 조직을 병리학적으로 관찰하였다. $CCl_4$의 투여로 AST, ALT, MDA가 증가하였으나 음양곽을 전처리하고 $CCl_4$를 후 투여한 경우에는 AST, ALT, MDA가 감소하였다. $CCl_4$의 투여로 SOD, catalase, GPx가 감소하였으나 음양 곽 전처리 한 후 $CCl_4$를 투여 한 경우에는 SOD, catalase, GPx가 증가하였다. 음양곽은 $CCl_4$로 유도된 free radicals를 scavenging함으로써 간독성을 경감시키는 것으로 사료된다. 위의 생리활성과 항산화계 변화 지표에서 나타난 음양곽의 간기능 보호효과를 형태학적으로 확인하기 위한 조직병리학적 검사결과 음양곽이 세포막의 소기관들을 과산화로부터 보호함으로써 효소활성의 최적구조를 유지시켜 간 손상을 완화시키는 것으로 사료된다.

Riboflavin Tetrabutylate가 약물대사 효소 및 지질 과산화효소에 미치는 영향 (Effect of Riboflavin Tetrabutylate on the Activity of Drug Metabolizing Enzyme and Lipid Peroxidation in Liver Microsomes of Rats)

  • 이향우;김원준;홍사석;곽창열;홍사오
    • 대한약리학회지
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    • 제16권2호
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    • pp.45-53
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    • 1980
  • Lipid peroxidation in vitro has been identified as a basic deteriorative reaction in cellular mechanism of aging processes, such as air pollution oxidant damage to cell and to the lung, chlorinated hydrocarbon hepatotoxicity. Many experimental evidences were reported by several investigators that lipid peroxidation could be one of the principle causes for the hepatotoxicity produced by $CCl_4$. It is now reasonably established that $CCl_4$ is activated to a free radical in vivo, that lipid peroxidation occurs very quickly in microsomes prepared from damaged livers, that the peroxidation is associated with loss of enzyme activity of microsomes, and that various antioxidants can protect animals against the hepatotoxic effect of $CCl_4$. Recent studies have drawn attention to some other feature of microsomal lipid peroxidation. Incubation of liver microsomes in the presence of NADPH has led to a loss of cytochrome $P_{450}$. However, the presence of an antioxidant prevented lipid peroxidation and preserved cytochrome $P_{450}$. Decrease of cytochrome $P_{450}$ in microsomes under in vitro incubation can be enhanced by $CCl_4 and these changes were parallel to a loss of microsomal polyunsaturated fatty acid and formation of malonaldehyde. The primary purpose of this experiment was to study the effect of riboflavin tetrabutylate on lipid peroxidation, specially, the relationship between lipid peroxidation and drug metabolizing enzyme system which is located in smooth endoplasmic recticulum as well as the effect of ritoflavin tetrabutylate on drug metabolizing enzyme system of animal treated with $CCl_4$. Albino rats were used for experimental animal. In order to induce drug metabolizing enzyme system, phenobarbital was injected intraperitoneally. $CCl_$ and riboflavin tetrabutylate were given intraperitoneally as solution in olive oil. Microsomal fraction was isolated from liver of animals and TBA value as well as the activity of drug metabolizing enzyme were measured in the microsomal fractions. The results are summerized as following. 1) The secobarbital induced sleeping time of $CCl_4$ treated rat was about 2 times longer than that of the control group. However, the pretreatment with riboflavin tetrabutylate inhibited completely the lengthened sleeping time due to $CCl_4$ treatment. Furthermore TBA value was significantly increased in $CCl_4$ treated rat in comparison to control group tut the increase of TBA value was prevented by the pretreatment with riboflavin tetrabutylate. On the other hand, the activity of hepatic drug metabolizing enzyme was decreased in $CCl_4$ group, however, the pretreatment with riboflavin tetrabutylate also prevented the decrease of the enzyme activity caused by $CCl_4$. 2) The effect of riboflavin tetrabutylate on TBA value and the activity of drug metabolizing enzyme in vitro was similar to in vivo results. Incubation of liver microsome from rat in the presence of $CCl_4$, $Fe^{++}$, or ascorbic acid has led to the marked increase of TBA value, however, the addition of riboflavin tetrabutylate in incubation mixture prevented significantly the increase of TBA value, suggesting the inhibition of lipid peroxidation. In accordance with TBA value, the activity of drug metabolizing enzyme was inhibited in the presence of $CCl_4$, $Fe^{++}$, ascorbic acid but the addition of riboflavin tetrabutylate protected the loss of the enzyme activity in microsome under in vitro incubation.

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Synergistic Effects of Jerusalem Artichoke in Combination with Pegylated Interferon Alfa-2a and Ribavirin Against Hepatic Fibrosis in Rats

  • Abdel-Hamid, Nabil Mohie;Wahid, Ahmed;Nazmy, Maiiada Hassan;Eisa, Marwa Abdel-Moniem
    • Asian Pacific Journal of Cancer Prevention
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    • 제17권4호
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    • pp.1979-1985
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    • 2016
  • Background: Complementary and alternative medicine has been highly appreciated as a supportive regimen for classical treatment strategies. Here we offer a nutrition-based adjuvant therapy for liver fibrosis, a major risk factor for cirrhosis and hepatocellular carcinoma. Aim of the study: To evaluate the possible hepatoprotective effects of Jerusalem artichoke tubers (JAT) in combination with interferon and ribavirin. Materials and Methods: Twelve groups of rats were administered JAT, interferon and ribavirin either separately or in combination from day one of $CCL_4$ administration until the end of the study. Animals were killed after 8 weeks of $CCL_4$-induced hepatotoxicity. Results: Hepatocytes from rats treated with triple combination of interferon, ribavirin, and JAT showed more less normal architecture compared to $CCL_4$-treated rats. We also detected significantly higher hepatic protein expression levels of p53, BAX and transforming growth factor-${\beta}$ (TGF-${\beta}$) in the $CCL_4$-intoxicated group compared to normal controls, as evidenced by immunohistochemical staining and western blotting analyses. Addition of JAT as a supportive regimen improved response to ribavirin and interferon and effectively participated in retaining normal histopathological and biochemical criteria and significantly lowered protein expression of p53, BAX, and TGF-${\beta}$. Conclusions: We suggest that addition of JAT as a supportive r egimen to interferon and ribavirin effectively potentiates their anti-fibrotic effects.

Screening of Momordica dioica for Hepatoprotective, Antioxidant, and Antiinflammatory Activities

  • Shreedhara, C.S.;Vaidya, V.P.
    • Natural Product Sciences
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    • 제12권3호
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    • pp.157-161
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    • 2006
  • The alcoholic extract of Momordica dioica roots significantly reduced $CCl_4$ induced hepatotoxicity in rats upon oral administration (200 mg/kg), as judged from the serum enzyme levels [serum glutamate oxaloacetate transaminases (SGOT), serum glutamate pyruvate transminases (SGPT), and alkaline phosphatase (ALP)]. These results were comparable with sylimarin (1.25 mg/kg, p.o.). The alcoholic extract inhibited the formation of oxyten derived free radicals (ODFR) in vitro with $4000\;{\mu}g/ml$ ascorbic system. The alcoholic extract also significantly reduced carrageenan-induced paw edema when administered orally (200 mg/kg) and the activity was comparable with ibuprofen(200 mg/kg, p.o.).

An isolation of the active component of Carthamus tinctorius L. Semen and the evaluation of its hepato-protective effect

  • Jeong, Jeong-Suk;Jeong, Choon-Sik;Jung, Ki-Hwa
    • 한국응용약물학회:학술대회논문집
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    • 한국응용약물학회 1998년도 Proceedings of UNESCO-internetwork Cooperative Regional Seminar and Workshop on Bioassay Guided Isolation of Bioactive Substances from Natural Products and Microbial Products
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    • pp.179-179
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    • 1998
  • We previously reported the hepato-protective effect of butanol soluble fraction of methanolic extract of Carthamus tinctorius L. Semen on carbon tetrachloride induced hepatotoxicity. In this study, the active component from the butanol soluble fraction was isolated by column chromatographic separation using Silica gel and Sephadex LH -20 and identified by spectroscopic methods such as Mass, $^1$H - NMR and $\^$13/C-NMR. The hepato-protective effect of the isolated active component on the CCl$_4$-induced liver damaged rats has been evaluated by performing blood chemical analysis and biotransformational enzyme analysis.

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산수유의 유리자유기에 의한 간손상 보호효과 및 기전에 대한 연구 (Study on the Protective Effect of Corni Fructus Against Free Radical Mediated Liver Damage)

  • 하기태;김영미;김철호;최달영;김준기
    • 동의생리병리학회지
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    • 제22권1호
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    • pp.82-88
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    • 2008
  • We evaluated the potential protective activity of the traditional Korean medicinal herb, Corni fructus (CF), in an experimental model of hepatotoxicity induced by carbontetrachloride $(CCl_4)$. The CF exhibited a hepatoprotective activity against Chang cell. And The expression of cytochrome P450 2E1 (CYP2E1), measured by RT-PCR and western blot, was significantly decreased in the CF treated Chang cell. But $CCl_4$ and CF has no significant effect on 1A1 and 3A1 isoform of cytochrome P450. Based on these findings, it is suggested that hepatoprotective effects of CF possibly related to antioxidative effects and downregulation of CYP2E1 expression.

Opuntia ficus-indica가 과산화지질 및 콜레스테롤에 미치는 영향 (Effects of Opuntia ficus-indica on Lipidperoxide and cholesterol level)

  • 전홍기;정영기;하배진
    • 생명과학회지
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    • 제13권6호
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    • pp.865-870
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    • 2003
  • 본 연구는 손바닥 선인장 투여 후 급성 $CCl_4$ 로 처리한 흰쥐의 간과 혈청을 사용하여, total cholesterol, HDL-cholesterol, LDL-cholesterol, total lipid, triglyceride (TG)를 간조직중에서 MDA를 측정함으로써 과산화지질 활성도와 콜레스테롤의 양을 조사하였다 OFC군은 손바닥 선인장 200mg/kg을, CTA 군은 saline을 2주간 매일 투여한 다음 간 손상의 유도는 사염화탄소를 olive oil에 1:1 비율로 용해시켜 체중 1kg당 50% $3.3m\ell$ 의용량을 복강으로 해부하기 24시간 전에 반 투여, 12시간 전에 나머지 반 투여하였다. 그 후 10시간 절식 후 혈액과 간을 채취하여 관찰하였다. 간 조직 중의 과산화지질 함량은 CTA 군은 NCT 군에 대하여 31.9% 증가를 보였으나, OFC 군에서는 CTA 군에 대해 32.6% 감소하는 경향을 나타내었다. 혈중 total lipid와 TG의 양은 손바닥 선인장을 투여한 군 (OFC) 이 CTA 군에 비해 각각 16.8%, 52.3%의 유의성 있는 감소를 보였다. Total cholesterol과 LDL-cholesterol은 OFC 군이 CTA 군에 대해 각각 12.7% 17.4% 정도로 크게 감소되는 것으로 나타났다. HDL-cholesterol은 CTA 군이 NCT 군에 대해 42.8% 감소하였으나, 손바닥 선인장을 투여함으로써 CTA 군에 대해 19.7% 증가를 나타냈다. 동맥경화지수는 CTA 군이 NCT 군에 비해 3.6배 높고, OFC 군이 CTA 군에 비해 1.8배 낮은 것으로 나타났다. 이상의 결과로, 손바닥 선인장을 투여한 후 간 독성을 유발하였을 때 과산화지질 및 콜레스테롤이 유의적인 수준으로 억제되었다.

사염화탄소에 의해 유발된 흰쥐의 간독성에 미치는 흰점박이꽃무지 추출물의 간보호 효과 (Protective Effects of Extracts of Protaetia brevitarsis on Carbon tetrachloride-induced Hepatotoxicity in the Mice)

  • 전정우;권해용;조유영;여주홍;이희삼
    • 한국잠사곤충학회지
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    • 제50권2호
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    • pp.93-100
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    • 2012
  • 본 연구는 사염화탄소에 의하여 유발되는 지질과산화에 의한 간독성에 대한 흰점박이꽃무지 추출물의 보호효과를 일차배양한 간세포와 간독성 흰쥐에서 GPT, bile acid, bilirubin 등의 활성 지표를 통해 간독성 회복효과를 알아보고자 하였다. 사염화탄소로 유발시킨 일차배양 간세포에 대한 흰점박이꽃무지와 장수하늘소 추출물의 간독성 회복효과는 각각 41.2%와 8.4%로 흰점박이꽃무지 유충 추출물이 간독성 회복 효과가 높게 나타났으며, 용매 추출별로는 흰점박이꽃무지 메탄올 추출물보다는 물 추출물이 농도의존적으로 간독성 회복효과가 있음을 확인하였다. 사염화탄소에 의해 간독성이 유도된 흰쥐에 흰점박이꽃무지 물추출물 분획별로 처리하였을 때, 분자량 낮을수록 효과적이었으며, 분자량이 1,000이하의 분획물에서 32.1%로 간독성 회복 효과가 우수하였다. 또한 흰쥐에 사염화탄소를 복강투여로 간독성을 유발한 후 흰점박이꽃무지 물분획물을 경구투여할 경우에 혈청 GPT, bile acid와 bilirubin의 활성이 정상군보다는 높았지만 사염화탄소군보다 유의적으로 감소하였고, 간섬유화와 관련된 hydroxyproline의 생성 억제에서는 분자량이 1000이하의 분획물에서 사염화탄소군보다 유의성 있게 생성을 억제하여 간섬유화를 예방하는 것으로 확인하였다. 중심정맥 쪽에 아주 경미한 허혈성 변성 이외에는 다른 병변을 찾을 수 없었고 세포내에 organelle이 유지된 편이고 콜라겐 형성이 매우 많이 줄어들어 병리조직학적으로도 간보호 효과가 있었음을 확인하였다. 이에 간독성 지표 활성을 긍정적으로 결과를 확인한 흰점박이꽃무지 추출물의 간질환 치료보조제나 건강기능성식품 소재 개발 가능성을 확인하였다.

Propugnating Effect of Bark of Rhizophora mucronata Against Different Toxicants Viz Carbon Tetrachloride, Ethanol and Paracetamol on HepG2 Cell Lines

  • Jairaman, Chitra;Yacoob, Syed Ali Mohamed;Venkatraman, Anuradha;Nagarajan, Yogananth;Murugesan, Gnanadesigan
    • 대한약침학회지
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    • 제22권1호
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    • pp.41-48
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    • 2019
  • Objective: The aim of the study was to evaluate the hepatoprotective activity of the bark extract (Ethanol: Water) in the ratio of (3:1) of Rhizophora mucronata (BERM) by intoxicating the $HepG_2$ cell lines with different toxicants viz, $CCL_4$, Ethanol and Paracetamol with different concentrations of the extract were used. The $HepG_2$ cell lines were subjected to MTT Assay for studying the cytotoxicity. Methods: $HepG_2$ cells were plated using 96 well plate in 10% bovine serum, exposed to different toxicants viz, 2% $CCl_4$, 60% Ethanol and 14 mM Paracetamol respectively. The various test concentrations (18.85, 37.5, 75, 150 and $300{\mu}g/ml$) of bark extract of Rhizophora mucronata was added and incubated for 24 hours. Medium was removed after incubation period and 0.5 mg/ml MTT(3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) was added and again incubated for 4 hours at 37oC. Then MTT was removed the crystals was dissolved in DMSO and absorbance was measured at 570 nm. Results: The result showed that dose dependent increase in percentage of viability at the doses of 18.85, 37.5, 75, 150, $300{\mu}g/ml$. Te results for the $CCl_4$ intoxicated, at $300{\mu}g/ml$ of the concentration of the extract, the % of viable cells was found out to be 99.6%, for Ethanol intoxicated, 97.67%, and Paracetamol induced, 75.37%, IC50 was $21.53{\mu}g/ml$, $12.61{\mu}g/ml$ and $21.42{\mu}g/ml$ respectively. Conclusion: Thus, we conclude that, the extract possesses defensive effect against different toxicants and can be used as an alternate drug for hepatotoxicity.