Silymarin retards collagen accumulation in early and advanced biliary fibrosis secondary to complete bile duct obliteration in rats

Abstract

rate hepatic collagen accumulation even in advanced (biliary) Silymarin (SIL), a standardized plant extract containing fibrosis; and 3) PIIINP appears to be a suitable serum marker about 60% polyphenole silibinin, is used as a hepatoprotective to monitor the inhibition of hepatic fibrogenesis in this model agent. Its antifibrotic potential in chronic liver diseases has of biliary fibrosis. (HEPATOLOGY 1997;26:643-649.) not been explored. Therefore, we applied SIL to adult Wistar rats that were subjected to complete bile duct occlusion (BDO) by injection of sodium amidotrizoate (Ethibloc). ThisProven therapy that halts the progression of liver fibrosis treatment induces progressive portal fibrosis without signifior induces regression of established cirrhosis is urgently cant inflammation. Rats with sham-operation that received needed. For several reasons, such therapy is not available: SIL at 50 mg/kg/d (n Å 10) and rats with BDO alone (n Å 1) the evolution of fibrosis in man is usually slow; 2) fibrosis 20) served as controls, whereas groups of 20 animals were is difficult to quantify from needle biopsies; 3) sampling error fed SIL at a dose of 25 and 50 mg/kg/d during weeks 1 through poses a severe problem in small tissue specimens; and 4) 6 or doses of 50 mg/kg/d during weeks 4 through 6 of BDO.suitable animal models that mirror at least a subgroup of Animals were sacrificed after 6 weeks for determination of human chronic liver diseases are lacking. Serum markers blood chemistries, total and relative liver collagen (as hyof liver fibrosis that could be used as suitable noninvasive droxyproline [HYP]), and the serum aminoterminal propeppredictors of the enhanced synthesis and deposition of hetide of procollagen type III (PIIINP). BDO in untreated rats patic collagen, i.e., fibrogenesis, or its removal, i.e., fibrolysis, caused an almost ninefold increase in total liver collagen (16.1 would be an attractive alternative for monitoring patients { 3.1 vs. 1.8 { 0.4 mg HYP, P õ .001). SIL at 50 mg/kg/d under therapy with a potential antifibrotic agent. However, reduced total HYP by 30% to 35%, either when given from final proof that such parameters are clinically useful, alweek 1 through 6 or from week 4 through 6 after BDO (10. 6 though suggested in several recent reports, is still needed.1,2 { 2.7 and 10.2 { 3.9 mg HYP, both P õ .01 vs. BDO alone), For these reasons, we selected and improved the rat model whereas 25 mg/kg/d were ineffective. Because SIL at 50 mg/ of biliary fibrosis secondary to bile duct obstruction (BDO). kg/d also reduced the collagen content per gram of liver tissue, This model can induce progressive portal fibrosis and finally it acted as a true antifibrotic agent. The single value of PIIINP cirrhosis, being almost devoid of the generation of toxic radiat killing paralleled the antifibrotic activity of SIL with 11.6 cals, massive hepatocyte necrosis, or major inflammation. It { 3.8 and 9.9 { 3.7 vs. 15.3 { 5.2 mg/L in both high-dose therefore resembles human (biliary) liver fibrosis and allo...

Hepatoprotective effect of silymarin

“…The regulation of cysteine synthesis may subsequently contribute to the antioxidant defense [29] . Silymarin reduced collagen accumulation by 30% in biliary fibrosis induced in rats [30] . A study in humans reported a slight increase in the survival of patients with cirrhotic alcoholism compared with untreated controls [31] .…”

Depletion of Thymosin �4 Promotes the Proliferation, Migration, and Activation of Human Hepatic Stellate Cells

“…A total of 30 male Sprague-Dawley rats (200-250 g) underwent bile duct ligation surgery as described previously [17,18] and were sacrificed after 4 or 6 weeks. The animal study was approved by the Animal Care and Use Committee of Xinhua Hospital, Shanghai, China.…”

Protective Effect of Iridoid Glucosides fromBoschniakia rossicaon Acute Liver Injury Induced by Carbon Tetrachloride in Rats

“…15,16) Various plants used in traditional medicine contain significant amounts of iridoid glucosides. [8][9][10]21,22) Some iridoid and phenylpropanoid compounds have rencently been isolated from Boschniakia rossica and presumed to be responsible for its major pharmacological function.…”

“…13) By inhibiting lipid peroxidation, silymarin protects against the hepatic toxicity induced by a wide variety of agents. 14,15) Pharmacological studies have indicated that silymarin was not toxic, even at high doses. 16) To evaluate the hepatoprotective mechanism of BRI, serum tumor necrosis factor-(TNF-), hepatic inducible nitric oxide synthase (iNOS), liver oxidative stress and the antioxidative defense system, as well as cytochrome P450 2E1 (CYP2E1), were determined.…”