RESUMO
Reactive oxygen species (O2(*-), OH(-), H2O2) are known to play an important role in tumor initiation in hepatocarcinoma. Hepatocarcinoma was developed in the Swiss Albino rats by administration three doses of diethylnitrosamine (DEN) (200 mg/kg b. wt.) (i.p.) at 15 days interval. Quercetin (QC), herbal polyphenolic compound, is a potent anticancer drug. Clinical trials are difficult for its hydrophobic nature. To overcome this problem, our study was aimed to formulate soluble liver specific, galactosylated liposomal QC and to investigate its efficacy against hepatocarcinoma in rat model. Galactosylated liposomal QC was formulated and the suspension was introduced intravenously to rats (8.98 microM/kg) once in a week for 16 weeks. Hepatocarcinoma in rat model and its pathological improvement were evaluated histopathologically, histochemically and electron microscopically. Severe oxidative damage was noticed in the whole liver and its microsomal fraction of DEN treated rats. Huge numbers of hyperplastic nodules (HNs) with pre-neoplastic lesions appeared in rat liver by DEN administration. Galactosylated liposomal QC injections prevented DEN mediated development of hepatocarcinoma and oxidative damage in rat liver. Quercetin in liver specific galactosylated liposomal drug delivery system may be recommended as a potent therapeutic formulation against DEN-induced hepatocarcinoma.
Assuntos
Alquilantes/antagonistas & inibidores , Alquilantes/toxicidade , Anticarcinógenos , Antioxidantes/farmacologia , Carcinógenos/antagonistas & inibidores , Carcinógenos/toxicidade , Dietilnitrosamina/antagonistas & inibidores , Dietilnitrosamina/toxicidade , Neoplasias Hepáticas/prevenção & controle , Quercetina/farmacologia , Animais , Antioxidantes/administração & dosagem , Antioxidantes/metabolismo , Catalase/metabolismo , Portadores de Fármacos , Composição de Medicamentos , Galactose/química , Glutationa Peroxidase/metabolismo , Substâncias Intercalantes/química , Substâncias Intercalantes/farmacologia , Peroxidação de Lipídeos/efeitos dos fármacos , Lipossomos , Neoplasias Hepáticas/induzido quimicamente , Neoplasias Hepáticas Experimentais/induzido quimicamente , Neoplasias Hepáticas Experimentais/patologia , Masculino , Microscopia Eletrônica , Microssomos Hepáticos/efeitos dos fármacos , Microssomos Hepáticos/patologia , Tamanho do Órgão/efeitos dos fármacos , Quercetina/administração & dosagem , RatosRESUMO
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 microM/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.