Inhibition of carbon tetrachloride-induced liver injury by liposomes containing vitamin E

Yao, Tony; Esposti, Silvia Degli; Huang, Lu-Qi; Arnon, Ron; Spangenberger, A.; Zern, Mark Α.

doi:10.1152/ajpgi.1994.267.3.g476

Cited by 19 publications

(29 citation statements)

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“…The activated Kupffer cell population is expanded and the cells release cytokines that are crucial for HSC activation. 15 Antioxidants, such as vitamin E, reduce hepatocellular injury 16,17 and inhibit HSC activation and matrix production in normal mice and in patients with hepatitis C virus infection. 18,19 Activated Kupffer cells are a major source of the enhanced expression of TGF-and PDGF, two potent profibrogenic cytokines.…”

Section: Activation Of Hscmentioning

confidence: 99%

Hepatic stellate cells: a target for the treatment of liver fibrosis

Zern

2000

Journal of Gastroenterology

241

169

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Hepatic fibrosis is a wound-healing process that occurs when the liver is injured chronically. Hepatic stellate cells (HSC) are responsible for the excess production of extracellular matrix (ECM) components. The activation of HSC, a key issue in the pathogenesis of hepatic fibrosis, is mediated by various cytokines and reactive oxygen species released from the damaged hepatocytes and activated Kupffer cells. Therefore, inhibition of HSC activation and its related subsequent events, such as increased production of ECM components and enhanced proliferation, are crucial goals for intervention in the hepatic fibrogenesis cascade. This is especially true when the etiology is unknown or there is no established therapy for the cause of the chronic injury. This review explores the rationale for choosing HSC as a target for the pharmacological, molecular, and other novel therapeutics for hepatic fibrosis. One focus of this review is the inhibition of two cytokines, transforming growth factor-beta and platelet-derived growth factor, which are important in hepatic fibrogenesis. A number of new agents, such as Chinese herbal recipes and herbal extracts, silymarin, S-adenosyl-L-methionine, polyenylphosphatidylcholine, and pentoxifylline are also discussed.

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Section: Activation Of Hscmentioning

confidence: 99%

Hepatic stellate cells: a target for the treatment of liver fibrosis

Zern

2000

Journal of Gastroenterology

241

169

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“…8) It also protects against carbon tetrachloride-induced hepatotoxicity. 9,10) The a-tocopherol analogue, PMC (2,2,5,7,8-pentamethyl-6-hydroxychromane), in which the phytyl chain is replaced by a methyl group, is more hydrophilic than other a-tocopherol derivatives, and has potent radical scavenging activity and potent inhibition of nuclear factor-kB activity. 11,12) The antiperoxidative potency of PMC was approximately 18-times than that of a-tocopherol.…”

mentioning

confidence: 99%

The Protective Effects of PMC against Chronic Carbon Tetrachloride-Induced Hepatotoxicity in Vivo.

Hsiao

Lin

et al. 2001

Biological & Pharmaceutical Bulletin

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Many studies have shown that reactive oxygen species including oxygen free radicals are causative factors in the etiology of degenerative diseases, including some hepatopathies. 1)Carbon tetrachloride (CCl 4 ) is most frequently used as a chemical inducer of experimental liver cirrhosis.2) It has been suggested that hepatic necrosis caused by carbon tetrachloride involves bioactivation by the microsomal cytochrome P450-dependent monooxygenase system, resulting in the formation of trichloromethyl free radical and reactive oxygen species that initiate lipid peroxidation and protein oxidation.3) Free radicals in both in vitro and in vivo models have also been shown to modify and damage proteins, carbohydrates, and DNA. 4) Therefore, under such disseminated oxidative stress, biomembrane and bioactive molecules are disturbed or inactivated. Furthermore, hepatic microsomes, mitochondria, and the nuclei of hepatocytes are also impaired by lipid peroxide, with hepatocytes ultimately being destroyed. 5)According to in vitro and in vivo studies, several classical antioxidants have been shown to protect hepatocytes against lipid peroxidation or inflammation, therefore preventing the occurrence of hepatic necrosis.6,7) a-Tocopherol is well known for its antioxidant properties in biomembranes where it acts to prevent lipid peroxidation.8) It also protects against carbon tetrachloride-induced hepatotoxicity.9,10) The a-tocopherol analogue, PMC (2,2,5,7,8-pentamethyl-6-hydroxychromane), in which the phytyl chain is replaced by a methyl group, is more hydrophilic than other a-tocopherol derivatives, and has potent radical scavenging activity and potent inhibition of nuclear factor-kB activity.11,12) The antiperoxidative potency of PMC was approximately 18-times than that of a-tocopherol.12) Recently, we reported that PMC is a potentially effective antioxidant and antiplatelet agent through the inhibition of cyclooxygenase.13) Therefore, we suggested that PMC may be effective against diseases in which reactive oxygen species play a role as potent causative factors.In the present study, we examined and compared the relative inhibitory activities of PMC with silymarin in chronic carbon tetrachloride-induced liver injury in mice. We also evaluated the role of oxidative stress in this model of liver injury. MATERIALS AND METHODSMaterials PMC was obtained from Wako Pure Chemical Ind. (Osaka, Japan). Carbon tetrachloride, silymarin, hydrogen peroxide, sodium azide, 5,5Ј-dithiobis (2-nitro benzoic acid) (DTNB), 2-thiobarbituric acid and other reagents in the study were obtained from Sigma Chemical Co. (St Louis, MO, U.S.A.). Diagnostic kits for assaying alanine aminotransferase (GPT) and aspartate aminotransferase (GOT) were also purchased from Sigma.Animals Male ICR mice, 5 weeks old, weighing 20-25 g used in this study were obtained from the Laboratory Animal Center of National Taiwan University. All the animal experiments and care were performed according to the Guide for the Care and Use of Laboratory Animals (National Academy Pre...

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“…Conventional liposomes with a composition of egg PC/Cholesterol/NGPE (60:30:10 molar ratio) were prepared by a method described previously (Yao et al 1994). 14 C-labelled small unilamellar vesicles were also prepared by following the same method.…”

Section: Preparation Of Liposomes (Suvs)mentioning

confidence: 99%

Hepatitis B surface protein docked vesicular carrier for site specific delivery to liver

Khatri

Rawat

Mahor

et al. 2005

Journal of Drug Targeting

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The intrinsic liver tropism of liposomes can be augmented by the addition of targeting features such as the incorporation of hepatotropic elements of the hepatitis viruses. Hepatitis B virus is known to infect hepatocytes after viremia by asialoglycoprotein receptor mediated uptake. However, the specificity of hepatitis B virus surface protein (HBsAg) towards hepatocytes has confronting reports. In the present study, we evaluated the functional ability of HBsAg to be employed as a ligand for targeting hepatocytes. We prepared (14)C labeled small unilamellar vesicles (SUVs) composed of egg PC/Cholesterol/N-glutarylphosphatidylethanolamine (NGPE) in a 60:30:10 molar ratio. HBsAg was covalently linked to SUVs using a water-soluble carbodiimide (EDC) mediated conjugation with NGPE. In vitro cell binding and uptake studies revealed that bioprotein docked carrier system was efficiently taken up by HepG2 cells by the receptor mediated endocytosis. The biodistribution behaviour of plain and HBsAg coated liposomes was also examined followed by intravenous injection. The study revealed that almost 75% of the radioactivity was recovered in the liver after 4 h of injection that was nearly three-fold greater in magnitude than the plain liposomes. Further, fractionation of liver into liver parenchymal cells (PC) and non-parenchymal cells confirmed the preferential localization of the HBsAg coated liposomal carrier in the parenchymal cells.

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Inhibition of carbon tetrachloride-induced liver injury by liposomes containing vitamin E

Cited by 19 publications

References 0 publications

Hepatic stellate cells: a target for the treatment of liver fibrosis

Hepatic stellate cells: a target for the treatment of liver fibrosis

The Protective Effects of PMC against Chronic Carbon Tetrachloride-Induced Hepatotoxicity in Vivo.

Hepatitis B surface protein docked vesicular carrier for site specific delivery to liver

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