ABSTRACT
AIM: To investigate the mechanisms underlying the protective effects of quercetin-rutinoside (rutin) and its aglycone quercetin against CCl(4)-induced liver damage in mice. METHODS: BALB/cN mice were intraperitoneally administered rutin (10, 50, and 150 mg/kg) or quercetin (50 mg/kg) once daily for 5 consecutive days, followed by the intraperitoneal injection of CCl(4) in olive oil (2 mL/kg, 10% v/v). The animals were sacrificed 24 h later. Blood was collected for measuring the activities of ALT and AST, and the liver was excised for assessing Cu/Zn superoxide dismutase (SOD) activity, GSH and protein concentrations and also for immunoblotting. Portions of the livers were used for histology and immunohistochemistry. RESULTS: Pretreatment with rutin and, to a lesser extent, with quercetin significantly reduced the activity of plasma transaminases and improved the histological signs of acute liver damage in CCl(4)-intoxicated mice. Quercetin prevented the decrease in Cu/Zn SOD activity in CCl(4)-intoxicated mice more potently than rutin. However, it was less effective in the suppression of nitrotyrosine formation. Quercetin and, to a lesser extent, rutin attenuated the inflammation in the liver by down-regulating the CCl(4)-induced activation of nuclear factor-kappa B (NF-κB), tumor necrosis factor-α (TNF-α) and cyclooxygenase (COX-2). The expression of inducible nitric oxide synthase (iNOS) was more potently suppressed by rutin than by quercetin. Treatment with both flavonoids significantly increased NF-E2-related factor 2 (Nrf2) and heme oxygenase (HO-1) expression in injured livers, although quercetin was less effective than rutin at an equivalent dose. Quercetin more potently suppressed the expression of transforming growth factor-ß1 (TGF-ß1) than rutin. CONCLUSION: Rutin exerts stronger protection against nitrosative stress and hepatocellular damage but has weaker antioxidant and anti-inflammatory activities and antifibrotic potential than quercetin, which may be attributed to the presence of a rutinoside moiety in position 3 of the C ring.
Subject(s)
Carbon Tetrachloride Poisoning/complications , Chemical and Drug Induced Liver Injury/prevention & control , Free Radical Scavengers/therapeutic use , Liver/drug effects , Quercetin/therapeutic use , Rutin/therapeutic use , Animals , Biphenyl Compounds/chemistry , Carbon Tetrachloride Poisoning/enzymology , Carbon Tetrachloride Poisoning/pathology , Chemical and Drug Induced Liver Injury/enzymology , Chemical and Drug Induced Liver Injury/etiology , Chemical and Drug Induced Liver Injury/pathology , Dose-Response Relationship, Drug , Free Radical Scavengers/administration & dosage , Free Radical Scavengers/chemistry , Immunohistochemistry , Injections, Intraperitoneal , Liver/enzymology , Liver/pathology , Liver Function Tests , Male , Mice , Mice, Inbred BALB C , Molecular Structure , Nitric Oxide/chemistry , Oxidative Stress/drug effects , Picrates/chemistry , Quercetin/administration & dosage , Quercetin/chemistry , Rutin/administration & dosage , Rutin/chemistryABSTRACT
AIM OF THE STUDY: Dandelion (Taraxacum officinale) has been traditionally used in the treatment of various liver disorders. The present study was aimed to assess the efficacy of dandelion root water-ethanol extract (DWE) in carbon tetrachloride (CCl(4))-induced hepatic fibrosis. MATERIALS AND METHODS: The mice were treated with CCl(4) dissolved in olive oil (20%, v/v, 2 ml/kg) intraperitoneally (i.p.), twice a week for 4 weeks. DWE was administered i.p. once daily for next 10 days, in doses of 200 and 600 mg/kg of body weight. The degree of hepatic fibrosis was determined by hydroxyproline content and Mallory trichrome staining. Oxidative stress was determined by measuring hepatic superoxide dismutase (Cu/Zn SOD) activity. The expression and specific tissue distribution of glial fibrillary acidic protein (GFAP), alpha-smooth muscle actin (alpha-SMA), and metallothionein (MT) I/II in the liver were determined by immunohistochemistry. RESULTS: Hepatic Cu/Zn SOD activity has been decreased in intoxicated mice and normalized in DWE treated groups. MT I/II immunopositivity was strongly reduced in the CCl(4) group. DWE treatment successfully decreased hepatic fibrinous deposits, restored histological architecture, and modulate the expression of GFAP and alpha-SMA. Concomitantly, MT I/II expression increased in the DWE treated groups. CONCLUSIONS: Our results suggest the therapeutic effect of DWE on CCl(4)-induced liver fibrosis by the inactivation of hepatic stellate cells and the enhancement of hepatic regenerative capabilities. The present results provide scientific evidence to substantiate the traditional use of Taraxacum officinale root in hepatic disorders.