ABSTRACT
SUMMARY: Carbon tetrachloride (CCl4) is a manufactured chemical and does not occur naturally in the environment. CCl4 is a clear liquid that evaporates very easily. It has a sweet odor. CCl4 is toxic to the mammalian liver and is hepatocarcinogenic in both rats and mice. Rosemary (Rosmarinus Officinalis) is commonly used as a spice and flavoring agent in food processing. It is known for its antioxidant properties. The present study aims to investigate the antioxidant activity of rosmarinic acid (RA) on CCl4-induced liver toxicity in adult male albino rats. Forty adult male albino rats were divided into 4 groups with 10 rats in each group. Group I (control group). Group II animals received RA at a dose of 50 mg/kg/day by oral gavage for 4 weeks. Group III animals received CCl4 intraperitoneally at a dose of 3ml/kg twice weekly for 4 weeks. Group IV animals received CCl4 Plus RA. At the end of the experiment, liver specimens are processed for histological, immunohistochemical, EM and biochemical studies. Administration of RA deceased the elevated serum liver enzymes (AST, ALT, and ALP), elevated MDA level and immunoexpression of the proapoptotic protein (Bax) induced by CCl4. It increased reduced glutathione (GSH), glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), and immunoexpression of the antiapoptotic protein (Bcl2). It also improved the histological and ultrastructural changes induced by CCl4. It appears that Rosmarinic acid has protective effects against CCl4-induced hepatotoxicity as indicated by biochemical, histological, immunohistochemical and ultrastructural results.
RESUMEN: El tetracloruro de carbono (CCl4) es un producto químico fabricado y no se encuentra de forma natural en el medio ambiente. CCl4 es un líquido transparente que se evapora fácilmente; tiene un olor dulce. CCl4 es tóxico para el hígado de los mamíferos y es hepatocarcinogénico tanto en ratas como en ratones. El romero (Rosmarinus officinalis) se usa comúnmente como condimento y agente aromatizante en el procesamiento de alimentos. Es conocido por sus propiedades antioxidantes. El presente estudio tuvo como objetivo investigar la actividad antioxidante del ácido rosmarínico (RA) sobre la toxicidad hepática inducida por CCl4 en ratas albinas macho adultas. Se dividieron cuarenta ratas albinas macho adultas en 4 grupos con 10 ratas en cada grupo. Grupo I (grupo control). Los animales del grupo II recibieron AR a una dosis de 50 mg / kg / día por sonda oral durante 4 semanas. Los animales del grupo III recibieron CCl4 por vía intraperitoneal a una dosis de 3 ml / kg dos veces por semana durante 4 semanas. Los animales del grupo IV recibieron CCl4 Plus RA. Al final del experimento, las muestras de hígado se procesaron para estudios histológicos, inmunohistoquímicos, EM y bioquímicos. La administración de AR eliminó las enzimas hepáticas séricas elevadas (AST, ALT y ALP), el nivel elevado de MDA y la inmunoexpresión de la proteína proapoptótica (Bax) inducida por CCl4. Aumentó el glutatión reducido (GSH), glutatión peroxidasa (GSH-Px), la superóxido dismutasa (SOD) y la inmunoexpresión de la proteína antiapoptótica (Bcl2). También mejoró los cambios histológicos y ultraestructurales inducidos por CCl4. El ácido rosmarínico puede tener efectos protectores contra la hepatotoxicidad inducida por CCl4, tal como lo indican los resultados bioquímicos, histológicos, inmunohistoquímicos y ultraestructurales.
Subject(s)
Animals , Male , Mice , Carbon Tetrachloride/toxicity , Cinnamates/administration & dosage , Depsides/administration & dosage , Chemical and Drug Induced Liver Injury/drug therapy , Antioxidants/administration & dosage , Superoxide Dismutase/analysis , Immunohistochemistry , Cinnamates/pharmacology , Oxidative Stress/drug effects , Microscopy, Electron, Transmission , Depsides/pharmacology , Glutathione Peroxidase/analysis , Malondialdehyde/analysis , Antioxidants/pharmacologyABSTRACT
The effect of Picroliv on hepatic microsomal mixed-function oxidases (MFO) and glutathione conjugating enzyme system in cholestatic rats was studied. Bile duct ligation in male rats for one weeks caused significant increase in both serum sorbitol dehydrogenase activity and serum bile acide concentration indicating cholestatic liver injury. Furthermore, a rise in the hepatic hydroxyproline level indicating collagen accumulation was observed. As a result of these alterations, the hepatic microsomal MFO system was imparied as evidenced by a decrease in cytochrome P-450 system content and in the activities of NADPH-cytochrome C reductase and aminopyrine demethylase. While the hepatic glutathione content remained unaffected, the cytosolic glutathione S-transferase activity was clearly suppressed due to subchronic cholestasis. Oral administration of Picroliv (25 mg/kg/day for 21 days)--a standardized irioid glycoside fraction of Picrorhiza kurroa in bile ligation induced cholestatic rats, singnificantly prevented the biochemical changes induced in liver and serum of cholestatic rats. These results suggested that picroliv has anti-cholestatic activity which may be attributed to antioxidant property or it's specific role in protein synthesis.