Hepatoprotective Activity of Liposomal Flavonoid against Arsenite-Induced Liver Fibrosis

• Published in: The Journal of pharmacology and experimental therapeutics 2007-03, Vol.320 (3), p.994-1001
• Main Authors: Mandal, Ardhendu K, Das, Subhankar, Basu, Mukul K, Chakrabarti, Rohini N, Das, Nirmalendu
• Format: Article
• Language: English
• Subjects: Animals; Antioxidants - administration & dosage; Antioxidants - chemistry; Antioxidants - therapeutic use; Arsenites - toxicity; Collagen - metabolism; Galactosides - chemistry; Hydroxyproline - metabolism; Lipid Peroxidation - drug effects; Liposomes; Liver - drug effects; Liver - enzymology; Liver - metabolism; Liver - pathology; Liver Cirrhosis - chemically induced; Liver Cirrhosis - metabolism; Liver Cirrhosis - pathology; Liver Cirrhosis - prevention & control; Male; Membrane Fluidity - drug effects; Mitochondria, Liver - drug effects; Quercetin - administration & dosage; Quercetin - chemistry; Quercetin - therapeutic use; Rats; Rats, Inbred Strains; Sodium Compounds - toxicity
• ISSN: 0022-3565; 1521-0103
• DOI: 10.1124/jpet.106.114215

Arsenic, the environmental metalloid toxicant, is known to induce oxidative damage to liver and produce hepatic fibrosis. The theme of our study was to optimize and evaluate the therapeutic efficacy of galactosylated liposomal flavonoidal antioxidant, quercetin (QC), in combating arsenic-induced hepatic fibrogenesis. The rats of the hepatic damage group were injected s.c. a single dose of sodium arsenite (NaAsO 2 ) (100.06 μM/kg b. wt. in 0.5 ml of physiological saline). Hepatocytes and stellate cells were separated. Mitochondrial membranes were isolated from all those separated cells. Oxidative damage was monitored at different isolated subcellular parts of different hepatic cells. Liver fibrosis was also induced by the injection of NaAsO 2 . Galactosylated liposomal QC injection before NaAsO 2 treatment checked fibrogenesis completely by protecting the liver from oxidative attack in cellular and subcellular levels. The maximal protections from hepatocellular and fatty metamorphosis, necrosis, Kupffer cell hyperplasia, fibrosis, and in the deposition of collagen contents were observed and reconfirmed by our histopathological and histochemical analysis when rats were treated with galactosylated liposomal QC before NaAsO 2 injection. Application of galactosylated liposomal QC may be a potent therapeutic approach for NaAsO 2 -induced fibrogenesis through a complete protection against oxidative attack in cellular and subcellular parts of rat liver.