The Extracts from Natural Product Complex (DW) Suppress Lipid reroxidation and Inhibit Liver Fibrosis (Cirrhosis) in Rats

실험동물에서 복합천연물(DW)의 지질 과산화 억제와 간섬유화 저해 효과 검색

  • Published : 2001.10.01

Abstract

The chronic cholestasis induce to biliary liver fibrosis (cirrhosis) and the increased products of ROS(reactive oxygen species) cause to the liver damage. In this study ; the antioxidant and antifibrotic effect of dried extracts of oriental medicine (DW) was investigated under the liver fibrotic (cirrhotic) condition. The female Sprague-Dawley rats were divided in 5 groups (Normal, Op-2, Op-4, OpDW-2, OpDW-4). Except for normal group, the rats were induced to biliary liver fibrosis (cirrhosis) by the operation of bile duct ligation/scission (BDU/S) and were observed in 2 weeks or 4 weeks. And the prepared DW was treated p.o.2 ml/day/rats in 2 weeks or 4 weeks for OpDW groups. At the time of sacrifice, the liver, kidney, spleen were weighed and the ratio of organ weight/body weight was calculated. The MDA, the hyp and biochemical parameters (GOT GTP, ALP, t-bili) were measured in sera and liver tissue of rats. The biochemical change was observed on liver tissue. In the result, the hepatomegaly and spleenomegaly appeared in all BDL/S operated rats, and significantly lower liver weight was observed in OpDW-4 group compared with in Op-4 group (p<0.05). The level of clinical parameters in sera of all liver fibrosis (cirrhosis) developed rats was higher than in normal group. Especial1y, the value of GOT in OpDW-2 group and ALP in OpDW-4 group showed significantly lower than in Op-2 group and Op-4 group (p<0.01, p<0.005). The content of hyp in all operation groups was significantly higher than in normal group (p<0.05∼<0.005), and showed significantly lower value in the OpDW-4 group than in Op-4 group (p<0.05). The product of lipid peroxidationUDA) increased significantly under the fibrotic(cirrhotic) condition (p<0.05∼ <0.005), and the MDA value in OpDW-4 group decreased significantly in Op-4 group (p<0.005). The histological change (bile duct proliferation, fibrosis, collagen bundle) was similarly observed in Op-2 group and in OpDW-2 group, but the weak fibrosis and bile duct proliferation were observed in OpDW-4 group compared with in Op-4 group. In conclusion, lipid peroxidation and severe liver damage were activated by bile duct obstruction, and the measurement of MDA and hap can be useful monitor for the screening of antioxidant and antifibrotic effect in experimental liver fibrosis (cirrhosis). The 4 weeks treatment with DW extracts suppressed lipid peroxidation and inhibited fibrotic (cirrhotic) process in BDL/S operated rats.

Keywords

References

  1. Arch.lmmunol.Ther.Exp.(Warsz) v.49 no.2 Alcohol-related cirrhosis with pancreatitis.The role of oxidative stress in the progression of the disease Szuster-Ciesielska,A.;Daniluk,J.;Kandefr-Szerszen,M.
  2. GUT v.47 no.5 Evidence of a systemic phenomena for oxidative stress in cholestatic liver disease Ljubuncic,P.;Tanne,Z.;Bomzon,A.
  3. Pathol.Intern.Soc.Nephrol. v.59 no.2 Lipid Peroxidation in human proteinuric disease.Cell Biol.lmmunol Maria-Liisa,S.;Heikki,A.;Anni,H.;Fulvio,U.;Tom,M.;Antonella,R.;Dontscho,K.;Harry,H.
  4. Am.J.Kidney Dis. v.19 no.292 The role of reactive oxygen species in animal models of glomerular disease Diamond,J.R.
  5. Arthritis Rheum v.44 no.5 Enhanced in vivo lipid peroxidation in scleroderma spectrum disorders Cracoski,J.L.;Marpeau,C.;Carpentier,P.H.;Imbert,B.;Hunt,M.;Stanke-Labesque,F.;Bessard,G.
  6. Phytother.Res. v.15 no.3 Antioxidant action of Tinospora cordifolia root extract in alloxan diabetic rats Stanely Mainzen Prince,P.;Menon,V.P.
  7. Biochem.Soc.Trans. v.29 no.2 Lipoprotein oxidation and atherosclerosis Young,I.S.;McEneny,J.
  8. Circulation v.98 no.22 Effect of dietary patterns on measures of lipid peroxidation.Results from a randomized clinical trial Miller,E.R.;Appel,L.J.;Risby,T.H.
  9. Arch.Biochem.Biophys. v.288 no.481 Peroxynitrite-induced membrane lipid peroxidation;The cytotoxic potential of superoxide and nitric oxide Radi,R.;Beckman,J.S.;Bush,K.M.;Freeman,B.A.
  10. Nucleic Acids Res. v.12 no.2569 Ascorbate stimulation of PAT cells causes an increase in transcription rates and adecrease in degradation rates of procollagen mRNA Lyon,B.L.;Schwarz,R.I.
  11. J.Clin.Invest. v.96 no.2461 Activation of hepation of hepatic stellate cells by TGFα and collagen typeⅡs mediated by oxidative stress through c-myb expression Lee,K.S.;Bruck,M.;Houglum,K.;Chojkier,M.
  12. Anal.Biochem. v.95 no.351 Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction Ohkawa,H.;Ohishi,N.;Yagi,K.
  13. J.Clin.Invest v.71 no.429 Hepatic lipid peroxidation in vivo in rats with chronic iron overload. Bacon,B.R.;Tavill,A.S.;Brittenham,G.M.;Park,C.H.;Recknagel,R.O.
  14. Physiol.Rev. v.59 no.527 Hydroperoxide metaolism in mammalian organs Chance,B.;Sies,H.;Boveris,A.
  15. Clin.Chim.Acta v.215 no.41 Changes of lipid levels in blood and liver tissues of patients with obstructive jaundice Tasi,L.Y.;Lee,K.T.;Tsai,S.M.;Lee,S.C.;Yu,S.H.
  16. Kidney International v.57 no.2 Contribution of gamma glutamyl transpeptidase to oxidative damage of ischemic rat kidney Cutrin,J.C.;Zingaro,B.;Camandola,S.;Boveris,A.;Pompella,A.;Poli,G.
  17. J.Hepatol. v.28 no.3 Reduction in hepatic cytochrome P-450 is correlated to the degree of liver fat content in animal models of steatosis in the absence of inflammation Leclercq,I.;Horsmans,Y.;Desager,J-P;Delzenne,N.;Geubel,A.
  18. Hepatology v.29 no.719 Suppressive effects of estradiol on dimethylnitro-samine-induced fibrosis of the liver in rats Yasuda,M.;Shimizu,I.;Shiba,M.;Ito,S.;Ito,S.
  19. Hepatology v.6 no.225 Cell types involved in collagen and fibronectin production in nomal and frbrotic human liver Clement,B.;Grimaud,J.A.;Campion J.P.;Deugnier,Y.;Guillouzo,A.
  20. J.Clin.Invest. v.82 no.450 Collagen measured in primary culture of normal rat hepatocytes derives from lipocytes within the monolayer Mather,J.J.;Bissell,D.M.;Friedmann,S.L.;Roll,F.J.
  21. Proc.Nutr.Soc. v.53 no.77 Carotenoids;functions and fallacies Thurnham,D.I
  22. Lancet v.337 no.1 Risk of angina pectoris and plasma concentrations of vitamin A,C,and E and carotene Riemersma,R.A.;Wood,D.A.;Macintyre,CCA.;Elton,R.A.;Gey,K.F.;Oliver,M.F.
  23. C.Am.J.Clin.Nutr. v.57 no.787S Increased risk of cardiovascular disease at suboptimal plasma concen-trtions of essential antioxidants:An epidemiological update with special attention to carotene and vitamin Gey,K.F.;Moser,U.K.;Jordan,P.Stahelin,H.B.;Eichholzer,M.;Ludin,E.
  24. Phytother.Res. v.15 no.3 Antioxidant and hepatoprotective effects of punicalagin and puvicalin on acetaminophen induced liver damage in rats Lin,C.C.;Hsu,Y.F.;Lin,T.C.;Hsu,H.Y.
  25. Indian J.Exp.Biol. v.39 no.1 Hepatoprotective and antioxidant property of andrographis paniculata(Nees)in BHC induced liver damage in mice Trivedi,N.P.;Rawal,U.M.
  26. Hepatology v.29 no.149 Effects of Sho-saiko-to,a Japanese herbal medicine,on gepatic fibrosis in rats Shimizu,I.;Ma,Y.R.;Mizobuchi,Y.;Liu,F.;Miura,T.;Nakai,Y.;Yasuda,M.;Shiba,M.;Horie,T.;Amagaya,S.;Kawada,N.;Hori,H.;Ito,S.
  27. Arzneim-Forsch v.48 no.Ⅰ Ingibitory action of silybinin on low density lipoprotein oxidation Locher,R.;Suter,P.M.;Weyhenmeyer R.;Vetter,W.
  28. 四物 陽 設興가 CCl/sub4/ 中 에 미치는 에 關한 的 硏究 v.1 no.1 林正
  29. 약학회지 v.38 no.3 영지로부터 추출한 다당체의 실험적 간경화에 대한 섬유화 억제효과 박은전;김기영;김재백;김수웅;이승룡;손동환
  30. Z.Allg.Med. v.71 no.11531 Chronische Hepatitis-Antifibrotische Therapieausaetze Suhuppan,D.
  31. Hepatology v.10 no.414 Effect of ursodeoxycholic acid on bile acid metabolism in primary biliary cirrhosis Batta,A.K.;Saken,G.;Arora,R.;Sheffer,S.
  32. J.Ethnopharmacol. v.66 no.355 Hepatoprotective activity of leaves Cassia occidentalis against paracetamaol and ethyl alcohol intoxication in rats Jafri M,M.A.;Jalis,S.;Kalim,J.;Surender,S.
  33. Eur.J.Pharmacol. v.378 no.1 Strong antiproliferative effects of baicalein in culure rat hepatic stellate cells Inoue,T.;Jackson,E.K.
  34. Biol.Pharm.Bull. v.23 no.6 Hepatoprotective aliphatic glycosides from three Goodyera species Xiao-Ming,D.;Ning-Yi,S.;Yang,C.;Nobuta,I.;Yukihiro,S.
  35. J.Toxicology in press The bile duct obstruction stimulated lipid peroxidation and liver fibrosis(cirrhosis)in animal Kim,K.Y.;Suh,E.S.;Park,S.Y.;Lim,J.A.
  36. Br.J.Exp.Path. v.65 no.305 Prolonged bile duct obstruction:a new experimental model for cirrhosis in the rat Kountras,J.;Billing,B.H.;Scheuder,P.J.
  37. Anal.Biochem. v.112 no.70 A single method to determine nanogram levels of 4-hydroxyproline in biological tissue Jamall,I.S.;Finelli,V.N.
  38. Proc.Natl.Acad.Sci. v.87 no.1620 Apparent hydroxyl radical production by peroxynitrite; Implications for endothelial injury iron nitric oxide and superoxide Beckman,J.S.;Beckman,T.W.;Chen,J.;Marshall,P.A.;Freeman,B.A.
  39. Kidney Int. v.59 no.2 Lipid peroxidation in human proteinuric disease Solin,M.L.;Ahola,H.;Hatia,A.;Ursini,F.;Montine,T.;Roveri,A.;Kerjaschki,D.;Holthoefer,H.
  40. Kidney Int. v.45 no.352 Role of oxidants and proteases in glomerular injury Johnson,R.J.;Lovett,D.;Lehrer,R.I.Couser,W.G.;Klebanoff,S.;J.
  41. GUT v.26 no.114 Double blind controlled trial of d-penicillamine in patients with primary biliary cirrhosis Neubauer,J.;Cristensen,E.;Portmann,B.;Caballeri,J.;Rodes,J.;Ranek,L.
  42. Hepatology v.7 no.1025 A controlled clinical trial evaluating cyclosporin in the treatment of primary biliary cirrhosis:A preliminary report Wiesner,R.M.;Dickson,E.R.;Lindor,D.;Jorgensen,R.;LaRusso,N.F.;Baldus,W.
  43. Hepatology v.10 no.801 The intergrated value of serum procollagen Ⅲ peptide over time predicts hepatic hydroxyproline content and stainalble collagen in a model of dietary cirrhosis in the rat Ruwart,M.J.;Wilkinson,K.F.;Rus,B.D.;Vidmazr,T.J.Hahn,E.G.;Peters,K.M.;Hendley,K.S.;Appelman,H.D.;Kim,K.Y.;Schuppan,D.
  44. Biolog & Pharmaceut.Bulletin v.23 no.2 Artifibrotic effects of the methanol extract of Polygonum aviculare in fibrotic rats induced by bile duct ligation and scission Nan,J.X.;Park,E.J.;Kim,H.J.;Ko.G.Sohn,D.H.
  45. Hepatology v.7 no.1104 Effectiveness of colchichine in patients with cirrhosis Kershenobich,H.D.;Vargas.;Garcia-Tsao,G.;Perez-Tamayo,R.;Rojkind,M.
  46. Gastroenterology v.86 no.897 Glucocorticoids suppress formation of collagen by the hepatocyte:Studies in primary monlayer cutures of paraenchymal cells prepared from rat liver Guzelian,D.S.;Lindblad,W.J.;Diegelmann,R.F.
  47. J.Lab.Clin.Med. v.113 no.177 Preventive effect of malotiate on dimethylnitro-samine-induced liver fibrosis in the rat Ala-Kokko,L.;Stenback,F.;Ryhanen,L.
  48. Hepatology v.18 no.209A Interferon-gamma reduces liver injury and collagen deposition in dimethylnitrosamine-induced cirrhosis Svegliati Beroni,G.;Curto,P.;Recchioni,A.;Mancini,R.;Benedetti,A.;Jezequel,A.M.;Oralan,F.
  49. Hepatology v.17 no.486 Pentoxifylline prevents fibrosis in an animal model and ingibits platelet-derived growth factor-driven proliferation of fibroblasts Peterson,T.C.
  50. J.Hepatol. v.13 no.35 Fibrosis of the liver in rats induced by bile duct ligation:Effects of inhibition of prolyl 4-hydroxylase Boder,K.;Schwarting,G.;Kaule,G.;Gunzler,V.;Schmidt,E.
  51. Dig.Dis.Sci. v.45 no.10 Ursodeoxycholic acid suppresses extent of lipid peroxidation in diseased liver in experimental cholestatic liver disease Liubuncic,P.;Tanne,Z.;Bomzon,A.
  52. Dissertation Pharmakologische Pruefung potentieller Antifibrotika in einem Ratten-Leberfibrose-Modell sowie Ermittlung der Stoffwechselwege zirkulierender Prokollagen-Peptide Kim,K.Y.