Antioxidant activity of silybin in vivo during long-term iron overload in rats

Pietrangelo, Antonello; Borella, F; Casalgrandi, Giovanna; Montosi, Giuliana; Ceccarelli, Daniela; Gallesi, Daniela; Giovannini, Fabiola; Gasparetto, A; Masini, Alberto

doi:10.1016/0016-5085(95)90762-9

Cited by 149 publications

(76 citation statements)

References 37 publications

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“…Mitochondria are a target of oxidative stress, but also the main source of free radicals and the impairment in MRC activity is directly responsible for the increase in cellular ROS in a vicious cycle [13]. Our results are consistent with previous findings on MRC restoration by silibinin in a rodent model of iron overload [20] and with recent data in another model of NASH [39].…”

Section: Discussionsupporting

confidence: 92%

“…Although being used in clinical practice worldwide, its therapeutic efficacy has been questioned for years. Potent scavenging properties have been demonstrated in vitro and in vivo, in different hepatic and non-hepatic cells [18,19]; and strong evidences for silibinin therapeutic efficacy have been reported in different types of experimental liver injury [20][21][22].…”

Section: Introductionmentioning

confidence: 99%

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Silibinin improves hepatic and myocardial injury in mice with nonalcoholic steatohepatitis

Salamone¹,

Galvano²,

Marino³

et al. 2012

Digestive and Liver Disease

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a b s t r a c tBackground: Nonalcoholic fatty liver disease is a chronic metabolic disorder with significant impact on cardiovascular and liver mortality. Aims: In this study, we examined the effects of silibinin on liver and myocardium injury in an experimental model of nonalcoholic fatty liver disease. Methods: A four-week daily dose of silibinin (20 mg/kg i.p.) was administrated to db/db mice fed a methionine-choline deficient diet. Hepatic and myocardial histology, oxidative stress and inflammatory cytokines were evaluated. Results: Silibinin administration decreased HOMA-IR, serum ALT and markedly improved hepatic and myocardial damage. Silibinin reduced isoprostanes, 8-deoxyguanosine and nitrites/nitrates in the liver and in the heart of db/db fed the methionine-choline deficient diet, whereas glutathione levels were restored to lean mice levels in both tissues. Consistently, liver mitochondrial respiratory chain activity was significantly impaired in untreated mice and was completely restored in silibinin-treated animals. TNF-␣ was increased whereas IL-6 was decreased both in the liver and heart of db/db fed methionine-choline deficient diet. Silibinin reversed heart TNF-␣ and IL-6 expression to control mice levels. Indeed, liver JNK phosphorylation was reduced to control levels in treated animals. Conclusions: This study demonstrates a combined effectiveness of silibinin on improving liver and myocardial injury in experimental nonalcoholic fatty liver disease.

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Section: Discussionsupporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Silibinin improves hepatic and myocardial injury in mice with nonalcoholic steatohepatitis

Salamone¹,

Galvano²,

Marino³

et al. 2012

Digestive and Liver Disease

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“…The latter phenomenon might be particularly true for those species, such as aldehydes, which have a long half-life and can elict their effect far from the site of generation. 38 However, by using monospecific antisera to MDA-lysine adducts, which have been shown to be highly sensitive for the detection of aldehyde-protein adducts in livers of CCl 4 39 or iron-treated rats, 14,37 we did find a dramatic increase of specific signal, but this signal was confined to cells that accumulate iron, mainly nonparenchymal cells. 5,6 It might be argued that a minimal amount of low-molecular-weight iron-chelates and/or nanomolar amounts of aldehydes that escape immunochemical detections may accumulate within HSC and turn on specific genetic programs through an oxidant stress (in the case of iron) or by forming adducts with key cytoplasmic or nuclear proteins (in the case of aldehydes).…”

Section: Discussionmentioning

confidence: 72%

“…14,[33][34][35][36] Protein-MDA adducts have been also found in plasma and in the liver of iron-loaded rats, 14,37 and in vivo antioxidant treatment significantly decreases their production. 37 Although it is quite clear that accumulation of lipid peroxidation by-products is a phenomenon secondary to cell (mem- brane) damage induced by oxidant stress, their role as an initiator of fibrogenic events remains undefined in vivo. In fact, the possibility exists that lipid peroxidation by-products: 1) are generated inside the HSC by free-radical attack exerted on cellular membranes; or 2) reach the HSC from neighboring iron-loaded cells and enhance collagen gene expression.…”

Section: Discussionmentioning

confidence: 98%

Hepatic stellate cells are not subjected to oxidant stress during iron-induced fibrogenesis in rodents

et al. 1998

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Oxidant stress plays a key role in hepatic fibrogenesis. This study was undertaken to assess whether, during iron overload-associated liver fibrosis in vivo, oxidant stress occurs in hepatic stellate cells (HSC) during active fibrogenesis. Gerbils were treated with iron-dextran, and, after hepatic fibrosis developed, livers were subjected to various combination of in situ hybridization and immunocytochemistry analyses. In iron-treated animals, no specific accumulation of ferritin protein was found in collagen mRNAexpressing cells. Moreover, the activity of the iron regulatory protein, the main sensor of cellular iron status, was unchanged in HSC from iron-treated animals. Although a significant amount of malondialdehyde-protein adducts was detected in gerbil liver during fibrogenesis, accumulation of these lipid peroxidation by-products was restricted to iron-laden cells adjacent to activated HSC. In cultured gerbil HSC, iron, aldehydes, and other pro-oxidants were able to enhance the expression of an oxidant stressresponsive gene, heme oxygenase (HO), with no change in collagen mRNA accumulation. In keeping with these findings, we found that, in vivo, activation of HO gene was present in iron-filled nonparenchymal cell aggregates, but absent in HSC. In conclusion, the data indicate that during iron overload-associated fibrogenesis, HSC are not directly subjected to oxidant stress, but are likely to be activated by paracrine signals arising in neighboring cells. (HEPATOLOGY 1998;27:1611-1622

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“…25,26 Its pharmacological profile is well defined, and studies in cell culture and animal models clearly show its hepatoprotective action with little or no toxicity. 26,27,[33][34][35][36][37][38][39][40][41] Silymarin enhances the activity of hepatocyte RNA-polymerase I, 26 complexes toxic free iron, 33 protects the cell membrane from radical-induced damage, 34 and blocks the uptake of toxins such as Amanita phalloides toxin. 32,35 A potent scavenger, it prevents lipid peroxidation and normalizes the lipid profile of hepatocyte membranes.…”

Section: Studies Of Defined Formulations Of Herbal Medicinesmentioning

confidence: 99%

Herbal products for liver diseases: A therapeutic challenge for the new millennium

et al. 1999

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Antioxidant activity of silybin in vivo during long-term iron overload in rats

Cited by 149 publications

References 37 publications

Silibinin improves hepatic and myocardial injury in mice with nonalcoholic steatohepatitis

Silibinin improves hepatic and myocardial injury in mice with nonalcoholic steatohepatitis

Hepatic stellate cells are not subjected to oxidant stress during iron-induced fibrogenesis in rodents

Herbal products for liver diseases: A therapeutic challenge for the new millennium

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