Effects of Silymarin MZ-80 on Hepatic Oxidative Stress in Rats with Biliary Obstruction

Correa, José Antonio González; Cruz, J. P. De La; Gordillo, Jorge Esparza; Ureña, I.; Redondo, L; Cuesta, Felipe Sánchez de la

doi:10.1159/000056146

Cited by 15 publications

(12 citation statements)

References 31 publications

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“…The elevation in the status of vitamin E during SIL treatment indicated the antioxidant and free radical scavenging potential of SIL. The protective effects of SIL observed in this study are in accordance with the investigations of Gonzalez-Correa et al (2002), who observed the antioxidant effect of SIL against oxidative stress in rat brain. Further, Zielinska-Przyjemska and Wiktorowicz (2006) have also shown that silydianin, an important and major constituent of SIL, possesses excellent in vitro free radical scavenging activity.…”

Section: Discussionsupporting

confidence: 92%

Silymarin: An Effective Hepatoprotective Agent Against Diethylnitrosamine-Induced Hepatotoxicity in Rats

Pradeep

Chandrasekaran

Gobianand

et al. 2007

Pharmaceutical Biology

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This study investigates the putative hepatoprotective and antioxidant activity of silymarin (SIL) on diethylnitrosamine (DEN)-induced liver damage in male Wistar rats. A single intraperitoneal administration of DEN (200 mg=kg) to rats resulted in significantly elevated serum levels of AST, ALT, ALP, LDH, c-GT, and BIL compared with controls after 30 days in serum. In contrast, the liver tissue showed a significant decrease in the levels of AST, ALT, and ALP, and an increase in LDH and c-GT. Elevated levels of lipid peroxidation (LPO) were observed in the liver tissue after DEN administration. Quantitative analysis of catalase (CAT) and superoxide dismutase (SOD) revealed lower activities of these key antioxidant enzymes in the liver upon DEN administration. The status of antioxidant vitamins, vitamin C and vitamin E, were also found to be decreased in DEN-exposed rats. When rats with DEN-induced hepatotoxicity were treated with SIL (50 mg=kg, orally) for 30 days, the levels of AST, ALT, ALP, LDH, c-GT, and BIL reverted to near normalcy, whereas the hepatic concentration of CAT, SOD, vitamin C, and vitamin E were significantly increased, and that of LPO significantly lowered, when compared with DENexposed, untreated rats. These results suggest that SIL is able to significantly alleviate the hepatotoxicity and oxidative stress induced by DEN in rats.

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Section: Discussionsupporting

confidence: 92%

Silymarin: An Effective Hepatoprotective Agent Against Diethylnitrosamine-Induced Hepatotoxicity in Rats

Pradeep

Chandrasekaran

Gobianand

et al. 2007

Pharmaceutical Biology

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“…Genes related to antioxidation and liver functions were identified based on KEGG pathway database. 7 Previous reports indicated that silymarin exhibits antioxidant activity partly through restoration of intracellular glutathione levels and activation of antioxidation-related enzymes involved in druginduced and carcinogen-induced hepatotoxicity (20,29,30). Indeed, the intracellular glutathione levels of hepatocytes were significantly increased after silymarin treatment (Fig.…”

Section: Cancer Researchmentioning

confidence: 91%

Chemopreventive Effect of Silymarin on Liver Pathology in HBV X Protein Transgenic Mice

Kao

et al. 2008

Cancer Research

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There are currently limited therapeutic regimens available for effective treatment of hepatocellular carcinoma (HCC). Silymarin is a naturally derived polyphenolic antioxidant with hepatoprotective properties and is very widely used in clinical application; however, effect of silymarin on spontaneous HCC has not been studied. Silymarin was evaluated for its efficacy against spontaneous carcinogenesis using the HBV X protein (HBx) transgenic model. Silymarin was p.o. given to the HBx transgenic mice from 4 to 6 weeks of age. Our data indicated that silymarin has therapeutic effects on the early stages of liver damage, reversing fatty changes and recovering liver histopathology in a dose-dependent manner. To study the chemopreventive effects on the later stages of carcinogenesis, the mice at 13 months were split into a precancerous group and a group with significant liver carcinogenesis. After silymarin was given to the precancerous mice from 13 to 16 months of age, in contrast to an 80% incidence of HCC development in the untreated transgenic mice, no HCC was detected in any of these mice. Nonetheless, small hyperplastic nodules were detected in 86% of these precancerous mice. In the second group with notable HCC, silymarin was unable to block cancer progression. Although silymarin did not affect HBx expression, intracellular reactive oxygen species levels were decreased, cell proliferation was stimulated, and hepatocyte ultrastructure was found to significantly recover. In conclusion, silymarin exerts beneficial effects on the early stages of liver pathogenesis, preventing and delaying liver carcinogenesis. This drug should be considered as a potential chemopreventive agent for HBV-related hepatocarcinogenesis.

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“…Similarly, the bile salts (BSs) retained in cholestatic disorders due to the secretory failure are though to produce in part damaging effects by inducing oxidative stress [27,28], and SIL may counteract these harmful effects. This has been recently corroborated in experimental bileduct ligation, where SIL improves the antioxidant status of obstructed livers and prevents lipid peroxidation [29,30]. Oxidative stress is a major feature of alcoholic and non-alcoholic liver steatosis, and a key determinant of their progression to cirrhosis.…”

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confidence: 78%

Silymarin as a New Hepatoprotective Agent in Experimental Cholestasis: New Possibilities for an Ancient Medication

Crocenzi¹,

Roma²

2006

CMC

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Silymarin is a purified extract from milk thistle (Silybum marianun (L.) Gaertn), composed of a mixture of four isomeric flavonolignans: silibinin (its main, active component), isosilibinin, silydianin and silychristin. This extract has been empirically used as a remedy for almost 2000 years, and remains being used as a medicine for many types of acute and chronic liver diseases. Despite its routinely clinical use as hepatoprotectant, the mechanisms underlying its beneficial effects remain largely unknown. This review addresses in detail a number of recent studies showing a novel feature of silymarin as a hepatoprotective drug, namely: its anticholestatic properties in experimental models of hepatocellular cholestasis with clinical correlate. For this purpose, this review will cover the following aspects: 1. The chemistry of silymarin, including chemical composition and properties. 2. The current clinical applications of silymarin as a hepatoprotective agent, including the mechanisms by which silymarin is thought to exert its hepatoprotective properties, when known. 3. The physiological events involved in bile formation, and the mechanisms of hepatocellular cholestasis, focusing on cellular targets and mechanisms of action of drugs used to reproduce experimentally cholestatic diseases of clinical interest, in particular estrogens and monohydroxylated bile salts, where anticholestatic properties of silymarin have been tested so far. 4. The recent findings describing the impact of silymarin on normal bile secretion and its novel, anticholestatic properties in experimental models of cholestasis, with particular emphasis on the cellular/molecular mechanisms involved, including modulation of bile salt synthesis, biotransformation/depuration of cholestatic compounds, changes in transporter expression/activity, and evocation of signaling pathways.

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Effects of Silymarin MZ-80 on Hepatic Oxidative Stress in Rats with Biliary Obstruction

Cited by 15 publications

References 31 publications

Silymarin: An Effective Hepatoprotective Agent Against Diethylnitrosamine-Induced Hepatotoxicity in Rats

Silymarin: An Effective Hepatoprotective Agent Against Diethylnitrosamine-Induced Hepatotoxicity in Rats

Chemopreventive Effect of Silymarin on Liver Pathology in HBV X Protein Transgenic Mice

Silymarin as a New Hepatoprotective Agent in Experimental Cholestasis: New Possibilities for an Ancient Medication

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