Silybin exerts antioxidant effects and induces mitochondrial biogenesis in liver of rat with secondary biliary cirrhosis

Serviddio, Gaetano; Bellanti, Francesco; Stanca, Eleonora; Lunetti, Paola; Blonda, Maria; Tamborra, Rosanna; Siculella, Luisa; Vendemiale, Gianluigi; Capobianco, Loredana; Giudetti, Anna Maria

doi:10.1016/j.freeradbiomed.2014.05.002

Cited by 65 publications

(41 citation statements)

References 39 publications

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“…The antioxidant and anti-inflammatory properties of silybin are considered to be responsible for its hepatoprotective effects (Ligeret et al, 2008; Trappoliere et al, 2009). Recent reports have demonstrated that silybin is also associated with mitochondrial biogenesis and that it prevents mtROS production by increasing the activities of the superoxide dismutase and peroxidase enzymes in response to liver injury (Detaille et al, 2008; Serviddio et al, 2014). In addition, silybin promotes liver repair by membrane stabilization and immunomodulatory and liver-regenerating mechanisms (Polyak et al, 2007; Gharagozloo et al, 2008; Trouillas et al, 2008).…”

Section: Discussionmentioning

confidence: 99%

Activation of Sirtuin 3 by Silybin Attenuates Mitochondrial Dysfunction in Cisplatin-induced Acute Kidney Injury

Lai

et al. 2017

Front. Pharmacol.

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Silybin is a secondary metabolite isolated from the seeds of blessed milk thistle (Silybum marianum) that has anti-inflammatory, antioxidative, antifibrotic, and antitumor properties. Here, we showed that silybin protected against cisplatin-induced acute kidney injury (AKI) by improving mitochondrial function through the regulation of sirtuin 3 (SIRT3) expression. Male SV129 and SIRT3 knockout (KO) mice were administered a single intraperitoneal (i.p.) injection of cisplatin with or without treatment with silybin. Moreover, cultured HK2 cells were used to evaluate mitochondrial morphology and function. Our data suggested that silybin enhanced SIRT3 expression after cisplatin administration both in vivo and in vitro. Silybin treatment improved mitochondrial function and bioenergetics in wild-type, but not SIRT3-defective, cells and mice. Moreover, we demonstrated that silybin markedly attenuated cisplatin-induced AKI and tubular cell apoptosis and improved cell regeneration in a SIRT3-dependent manner. Collectively, these results suggest that silybin is a pharmacological activator of SIRT3 capable of protecting against cisplatin-induced tubular cell apoptosis and AKI by improving mitochondrial function. Thus, silybin could serve as a potential clinical renoprotective adjuvant treatment in cisplatin chemotherapy.

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Section: Discussionmentioning

confidence: 99%

Activation of Sirtuin 3 by Silybin Attenuates Mitochondrial Dysfunction in Cisplatin-induced Acute Kidney Injury

Lai

et al. 2017

Front. Pharmacol.

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“…The primers used for Dloop and Gapdh, mitochondrial and nuclear specific DNA sequences respectively, are reported in Table 1. mtDNA level was expressed as the ratio of mtDNA to nuclear DNA quantity (mtDNA/nDNA) (Serviddio et al, 2014). …”

Section: Methodsmentioning

confidence: 99%

β-Catenin Knockdown Affects Mitochondrial Biogenesis and Lipid Metabolism in Breast Cancer Cells

et al. 2017

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β-catenin plays an important role as regulatory hub in several cellular processes including cell adhesion, metabolism, and epithelial mesenchymal transition. This is mainly achieved by its dual role as structural component of cadherin-based adherens junctions, and as a key nuclear effector of the Wnt pathway. For this dual role, different classes of proteins are differentially regulated via β-catenin dependent mechanisms. Here, we applied a liquid chromatography-mass spectrometry (LC-MS/MS) approach to identify proteins modulated after β-catenin knockdown in the breast cancer cell line MCF-7. We used a label free analysis to compare trypsin-digested proteins from CTR (shCTR) and β-catenin knockout cells (shβcat). This led to the identification of 98 differentially expressed proteins, 53 of them were up-regulated and 45 down-regulated. Loss of β-catenin induced morphological changes and a significant modulation of the expression levels of proteins associated with primary metabolic processes. In detail, proteins involved in carbohydrate metabolism and tricarboxylic acid cycle were found to be down-regulated, whereas proteins associated to lipid metabolism were found up-regulated in shβcat compared to shCTR. A loss of mitochondrial mass and membrane potential was also assessed by fluorescent probes in shβcat cells with respect to the controls. These data are consistent with the reduced expression of transcriptional factors regulating mitochondrial biogenesis detected in shβcat cells. β-catenin driven metabolic reprogramming resulted also in a significant modulation of lipogenic enzyme expression and activity. Compared to controls, β-catenin knockout cells showed increased incorporation of [1-14 C]acetate and decreased utilization of [U-14 C]glucose for fatty acid synthesis. Our data highlight a role of β-catenin in the regulation of metabolism and energy homeostasis in breast cancer cells.

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“…Recently, multiple dynamic mechanisms regulating mitochondrial quality control in mammals have been identified; mitochondrial dynamics including fission/fusion, selective mitochondrial autophagy (mitophagy) and mitochondrial biogenesis (regulating mitochondrial number for cellular adaptation) . Failure of mitophagy or mitochondrial biogenesis affects hepatocellular function during ischemia/reperfusion and cholestasis . Moreover, interplay between these processes and oxidative metabolism, which may contribute to hepatic cell damage, has been suggested to occur in the steatotic liver .…”

Section: Introductionmentioning

confidence: 99%

Melatonin enhances mitophagy and mitochondrial biogenesis in rats with carbon tetrachloride‐induced liver fibrosis

Kang

Hong

Lee

2016

Journal of Pineal Research

201

161

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Liver fibrosis leads to liver cirrhosis and failure, and no effective treatment is currently available. Growing evidence supports a link between mitochondrial dysfunction and liver fibrogenesis and mitochondrial quality control-based therapy has emerged as a new therapeutic target. We investigated the protective mechanisms of melatonin against mitochondrial dysfunction-involved liver fibrosis, focusing on mitophagy and mitochondrial biogenesis. Rats were treated with carbon tetrachloride (CCl4) dissolved in olive oil (0.5 mL/kg, twice a week, i.p.) for 8 wk. Melatonin was administered orally at 2.5, 5, and 10 mg/kg once a day. Chronic CCl4 exposure induced collagen deposition, hepatocellular damage, and oxidative stress, and melatonin attenuated these increases. Increases in mRNA and protein expression levels of transforming growth factor β1 and α-smooth muscle actin in response to CCl4 were attenuated by melatonin. Melatonin attenuated hallmarks of mitochondrial dysfunction, such as mitochondrial swelling and glutamate dehydrogenase release. Chronic CCl4 exposure impaired mitophagy and mitochondrial biogenesis, and melatonin attenuated this impairment, as indicated by increases in mitochondrial DNA and in protein levels of PTEN-induced putative kinase 1 (PINK1); Parkin; peroxisome proliferator-activated receptor-gamma coactivator 1α (PGC-1α); nuclear respiratory factor 1 (NRF1); and transcription factor A, mitochondrial (TFAM). CCl4-mediated decreases in mitochondrial fission- and fusion-related proteins, such as dynamin-related protein 1 (DRP1) and mitofusin 2, were also attenuated by melatonin. Moreover, melatonin induced AMP-activated protein kinase (AMPK) phosphorylation. These results suggest that melatonin protects against liver fibrosis via upregulation of mitophagy and mitochondrial biogenesis, and may be useful as an anti-fibrotic treatment.

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Silybin exerts antioxidant effects and induces mitochondrial biogenesis in liver of rat with secondary biliary cirrhosis

Cited by 65 publications

References 39 publications

Activation of Sirtuin 3 by Silybin Attenuates Mitochondrial Dysfunction in Cisplatin-induced Acute Kidney Injury

Activation of Sirtuin 3 by Silybin Attenuates Mitochondrial Dysfunction in Cisplatin-induced Acute Kidney Injury

β-Catenin Knockdown Affects Mitochondrial Biogenesis and Lipid Metabolism in Breast Cancer Cells

Melatonin enhances mitophagy and mitochondrial biogenesis in rats with carbon tetrachloride‐induced liver fibrosis

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