Silymarin Retards the Progression of Alcohol-Induced Hepatic Fibrosis in Baboons

Lieber, Charles S.; Leo, Maria A.; Cao, Qi; Ren, Chaoling; DeCarli, Leonore M.

doi:10.1097/00004836-200310000-00013

Cited by 135 publications

(87 citation statements)

References 9 publications

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“…Such compounds show protective effects against agent-induced hepatic injuries (Berger & Kowdley, 2003;Lieber et al, 2003;Hedayat et al, 2004). Other studies state that silymarin exhibited antioxidant action (Soto et al, 2003;Chlopcikova et al, 2004;Lieber, 2004) and showed promising antineoplastic and immunomodulatory effects (Amirghofran et al, 2000;Hannay & Yu, 2003;Schümann et al, 2003;Yoo et al, 2004).…”

Section: Discussionmentioning

confidence: 99%

Antioxidant and hepatoprotective activities of Egyptian moraceous plants against carbon tetrachloride-induced oxidative stress and liver damage in rats

Singab

Ayoub

Ali

et al. 2010

Pharmaceutical Biology

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Section: Discussionmentioning

confidence: 99%

Antioxidant and hepatoprotective activities of Egyptian moraceous plants against carbon tetrachloride-induced oxidative stress and liver damage in rats

Singab

Ayoub

Ali

et al. 2010

Pharmaceutical Biology

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“…S. marianum or milk thistle (MT) is the most well-researched plant in the treatment of liver disease and has been used to treat ALD and acute and chronic viral hepatitis. In baboons, the active principle called silymarin, administered for 3 years, retarded the development of alcohol-induced hepatic fibrosis [195] . The major mechanism of its hepatoprotective activity is the inhibition of hepatic NF-κB activation.…”

Section: Therapeutic Optionsmentioning

confidence: 99%

Pathogenesis of alcoholic liver disease: Role of oxidative metabolism

Ceni

Mello

Galli

2014

WJG

415

339

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Alcohol consumption is a predominant etiological factor in the pathogenesis of chronic liver diseases, resulting in fatty liver, alcoholic hepatitis, fibrosis/cirrhosis, and hepatocellular carcinoma (HCC). Although the pathogenesis of alcoholic liver disease (ALD) involves complex and still unclear biological processes, the oxidative metabolites of ethanol such as acetaldehyde and reactive oxygen species (ROS) play a preeminent role in the clinical and pathological spectrum of ALD. Ethanol oxidative metabolism influences intracellular signaling pathways and deranges the transcriptional control of several genes, leading to fat accumulation, fibrogenesis and activation of innate and adaptive immunity. Acetaldehyde is known to be toxic to the liver and alters lipid homeostasis, decreasing peroxisome proliferator-activated receptors and increasing sterol regulatory element binding protein activity via an AMP-activated protein kinase (AMPK)-dependent mechanism. AMPK activation by ROS modulates autophagy, which has an important role in removing lipid droplets. Acetaldehyde and aldehydes generated from lipid peroxidation induce collagen synthesis by their ability to form protein adducts that activate transforming-growth-factor-β-dependent and independent profibrogenic pathways in activated hepatic stellate cells (HSCs). Furthermore, activation of innate and adaptive immunity in response to ethanol metabolism plays a key role in the development and progression of ALD. Acetaldehyde alters the intestinal barrier and promote lipopolysaccharide (LPS) translocation by disrupting tight and adherent junctions in human colonic mucosa. Acetaldehyde and LPS induce Kupffer cells to release ROS and proinflammatory cytokines and chemokines that contribute to neutrophils infiltration. In addition, alcohol consumption inhibits natural killer cells that are cytotoxic to HSCs and thus have an important antifibrotic function in the liver. Ethanol metabolism may also interfere with cell-mediated adaptive immunity by impairing proteasome function in macrophages and dendritic cells, and consequently alters allogenic antigen presentation. Finally, acetaldehyde and ROS have a role in alcohol-related carcinogenesis because they can form DNA adducts that are prone to mutagenesis, and they interfere with methylation, synthesis and repair of DNA, thereby increasing HCC susceptibility. Key words: Alcohol metabolism; Acetaldehyde; Reactive oxygen species; Alcoholic liver disease; Protein adducts; Hepatic stellate cells; Liver fibrosis; CYP2E1Core tip: The goal of this article is to review the mechanisms of alcohol-mediated toxicity in parenchymal and non-parenchymal cells of the liver. Specifically, we highlight the effect of oxidative ethanol metabolites such as acetaldehyde and reactive oxygen species in the development of fat accumulation, fibrosis and deranged immune response.Ceni E, Mello T, Galli A. Pathogenesis of alcoholic liver disease: Role of oxidative metabolism.

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“…Silymarin suppressed the expression of pro-fibrogenic procollagen-α1(I) and TIMP-1 most likely via down-regulation of TGF-β1 mRNA in the rats with biliary fibrosis (Jia et al 2001). Silymarin, administered during three years, retarded the development of alcohol-induced hepatic fibrosis in baboons (Lieber et al, 2003).…”

Section: Antifibrotic Activitymentioning

confidence: 99%

Milk thistle in liver diseases: past, present, future

Abenavoli

Capasso²,

Milić

et al. 2010

Phytotherapy Research

503

350

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Silybum marianum or milk thistle (MT) is the most well‐researched plant in the treatment of liver disease. The active complex of MT is a lipophilic extract from the seeds of the plant and is composed of three isomer flavonolignans (silybin, silydianin, and silychristin) collectively known as silymarin. Silybin is a component with the greatest degree of biological activity and makes up 50% to 70% of silymarin. Silymarin is found in the entire plant but it is concentrated in the fruit and seeds. Silymarin acts as an antioxidant by reducing free radical production and lipid peroxidation, has antifibrotic activity and may act as a toxin blockade agent by inhibiting binding of toxins to the hepatocyte cell membrane receptors. In animals, silymarin reduces liver injury caused by acetaminophen, carbon tetrachloride, radiation, iron overload, phenylhydrazine, alcohol, cold ischaemia and Amanita phalloides. Silymarin has been used to treat alcoholic liver disease, acute and chronic viral hepatitis and toxin‐induced liver diseases. Copyright © 2010 John Wiley & Sons, Ltd.

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Silymarin Retards the Progression of Alcohol-Induced Hepatic Fibrosis in Baboons

Cited by 135 publications

References 9 publications

Antioxidant and hepatoprotective activities of Egyptian moraceous plants against carbon tetrachloride-induced oxidative stress and liver damage in rats

Antioxidant and hepatoprotective activities of Egyptian moraceous plants against carbon tetrachloride-induced oxidative stress and liver damage in rats

Pathogenesis of alcoholic liver disease: Role of oxidative metabolism

Milk thistle in liver diseases: past, present, future

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