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Query: UMLS:C0023890 (cirrhosis)
 42,195 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cirrhosis of the liver is a major complication of various chronic liver diseases and results from excess production and decreased degradation of extracellular matrix. Proinflammatory cytokines, toxic metabolites and certain drugs can trigger enhanced fibrogenesis in hepatic stellate cells and myofibroblasts, the major matrix-producing cells. Since treatment of established cirrhosis is limited, therapeutic interventions that inhibit or mitigate fibrogenesis are needed. Numerous drugs have been investigated for their antifibrotic potential and botanicals constitute a significant fraction of them. Colchicine has been used to treat various chronic liver diseases with controversial results. To date, there is a lack of studies in appropriate animal models and well-controlled human trials to demonstrate its antifibrotic properties. Silymarin has so far failed to clearly show an antifibrotic effect in human studies, whereas animal experiments suggest that this mixture of flavolignanes may be beneficial in patients which have not yet developed cirrhosis. Animal studies indicate an antifibrotic potential of Shosaiko-to, a herbal combination frequently used in China and Japan for the treatment of chronic viral hepatitis, but mechanisms of action need to be further explored. Other botanicals include trans-resveratrol, a flavonoid extracted from grapevine, and Salvia miltiorrhiza which were shown to interfere with the process of hepatic stellate cell activation. Herbal combinations, such as compound 861 and LIV.52 were advocated as antifibrotics or hepatoprotectives, but studies in humans have either been of questionable design or resulted in cessation of the trial due to adverse outcomes.
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PMID:Antifibrotic properties of botanicals in chronic liver disease. 1214 13

Liver cirrhosis (LC) is a chronic disease with high mortality rate and its pathophysiology includes hepatic parenchymal cell destruction, connective tissue formation, and nodular regeneration. Colchicine has been used in liver diseases as an anti-inflammatory and anti-fibrotic drug. However, there is controversy over the beneficial effects of colchicine in LC treatment. In the present study, we injected rats with multiple doses of dimethylnitrosamine for 4 weeks and used rats with severe LC to determine whether colchicine treatment improved liver functions and resolved cirrhotic nodules. Colchicine (30-150microg/kg per day, i.p., for 4 weeks) failed to significantly increase the survival rate of LC rats. Animals were subjected to blood biochemical, liver histopathological and immunochemical analyses. The plasma albumin level, decreased in cirrhotic rats, was restored by colchicine treatment along with reduction of ascites. Colchicine decreased the accumulated extracellular matrix and the multiple fibrotic nodules formed in cirrhotic liver, and eliminated alpha-smooth muscle actin (alpha-SMA)-positive cells. In activated stellate cells, colchicine inhibited alpha-SMA and transforming growth factor-beta1 (TGFbeta1) expression. The results of the present study showed that colchicine resolves cirrhotic nodules and accumulated fibers in the liver of LC rats, but failed to significantly improve the survival rate of LC animals, and that the beneficial effects of colchicine in cirrhotic animals result from stellate cell inactivation and inhibition of TGFbeta1 expression.
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PMID:Effects of colchicine on liver functions of cirrhotic rats: beneficial effects result from stellate cell inactivation and inhibition of TGF beta1 expression. 1472 49

The purpose of this work was to obtain a suitable model of fibrosis, in which spontaneous reversion was minimal, to study the ability of silymarin, silibinin, colchicine and trimethylcolchicinic acid (TMCA) to reverse it. Reversal of liver fibrosis was studied in male Wistar rats after one, two or three months of CCl(4) administration (0.4 g/kg intraperitoneally, three times per week), by discontinuation of the toxin for 2 months. Silymarin (50 mg/kg), silibinin (50 mg/kg), colchicine (10 microg/rat) and trimethylcolchicinic acid (100 microg/rat) were administered daily, by gavage, after 3 months of CCl(4) administration. Collagen content was determined by measuring hydroxyproline in liver samples; glycogen, was determined utilizing the anthrone reagent; Mallory's trichromic stains of liver sections were performed. The best scheme of treatment was obtained when CCl(4) was administered during three months (collagen increased 6 times). Discontinuation of the toxin for two months produced a significant but relative small reduction of fibrosis (collagen was still 4.5 times over control). Colchicine, TMCA, silymarin or silibinin treatment showed no significant fibrolitic effect. This scheme of treatment may be an excellent tool to study the ability of drugs to reverse fibrosis. The hepatoprotective properties of silymarin, silibinin, colchicine and trimethylcolchinic acid may be irrelevant to reverse established cirrhosis.
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PMID:Resolution of liver fibrosis in chronic CCl4 administration in the rat after discontinuation of treatment: effect of silymarin, silibinin, colchicine and trimethylcolchicinic acid. 1617 51

Colchicine, which has been reported to inhibit fibrosis, has been successfully used to treat fibrotic disorders, such as liver cirrhosis, scleroderma, and idiopathic pulmonary fibrosis. We hypothesized that besides its ability to prevent amyloid deposition, colchicine may prevent the development of interstitial fibrosis (IF) in amyloidosis patients who had undergone renal transplantation. We evaluated the influence of colchicine therapy on the development of IF in 25 patients with systemic amyloidosis secondary to familial Mediterranean fever (group 1). Twenty-five nonamyloidotic patients who did not receive colchicine therapy served as controls (group 2). The incidences of recurrence and development of IF in the first, second, and third years after transplantation were evaluated from follow-up allograft biopsies. Only four patients showed amyloid recurrence in their renal allografts. IF developed in 44% (11/25) of group 1 patients and 80% (20/25) of group 2 patients during the 36 months posttransplantation (P < .01). Development of IF in the first, second, and third years posttransplantation was significantly greater among group 2 recipients than group 1 recipients (P < .01). The overall 1-, 2-, and 3-year graft survival rates for group 1 recipients were 96%, 92%, and 80%, and those for group 2 recipients were 96%, 88%, and 60%, respectively. Our results support the thesis that colchicine therapy may help prevent the development of interstitial fibrosis in renal allografts.
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PMID:Does colchicine have an antifibrotic effect on development of interstitial fibrosis in renal allografts of recipients with familial Mediterranean fever? 1654 51


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