title: Hepatoprotective and antioxidant activity of Melaleuca styphelioides on carbon tetrachloride-induced hepatotoxicity in mice.
abstract: BACKGROUND
  Liver disease is a serious problem. Polyphenolic compounds have marked antioxidant effect and can prevent the liver damage caused by free radicals. In vitro studies have revealed the strong antioxidant activity of an ellagitannin-rich plant, namely, Melaleuca styphelioides Sm. (Myrtaceae).
  
  
  OBJECTIVE
  In view of the limited therapeutic options available for the treatment of liver diseases, the hepatoprotective potential of the methanol extract of M. styphelioides leaves (MSE) was investigated against CCl4-induced liver injury in mice.
  
  
  METHODS
  MSE was administered (500 and 1000 mg/kg/d p.o.) along with CCl4 for 6 weeks. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) were determined in the serum. Glutathione (GSH), superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GR), glutathione transferase (GST), and malondialdehyde (MDA) were estimated in the liver homogenate. The bioactive components of MSE were identified by NMR, UV and HRESI-MS/MS data.
  
  
  RESULTS
  MSE treatment (500 and 1000 mg/kg/d) markedly inhibited the CCl4-induced increase in the levels of AST (31 and 38%), ALT (29 and 32%), ALP (13 and 19%), and MDA (22 and 37%) at the tested doses, respectively. MSE treatment markedly increased the levels of GSH (29 and 57%) and antioxidant enzymes compared with the CCl4-treated group. MSE was more effective than silymarin in restoring the liver architecture and reducing the fatty changes, central vein congestion, Kupffer cell hyperplasia, inflammatory infiltration, and necrosis induced by CCl4. The LD50 of MSE was more than 5000 mg/kg.
  
  
  CONCLUSIONS
  MSE confers potent antioxidant and hepatoprotective effects against CCl4-induced toxicity.
authors.affiliation: Department of Pharmacognosy, Faculty of Pharmacy, Ain-Shams University , Cairo , Egypt .
authors.forename: Eman
authors.initials: E
authors.lastname: Al-Sayed
authors.forename: Naglaa M
authors.initials: NM
authors.lastname: El-Lakkany
authors.forename: Sayed H
authors.initials: SH
authors.lastname: Seif El-Din
authors.forename: Abdel-Nasser A
authors.initials: AN
authors.lastname: Sabra
authors.forename: Olfat A
authors.initials: OA
authors.lastname: Hammam
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity; D002251:Carbon Tetrachloride / Q000633:toxicity; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D007928:Lethal Dose 50; D008107:Liver Diseases / Q000517:prevention & control*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D031650:Melaleuca / Q000737:chemistry*; D051379:Mice; D010936:Plant Extracts / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity; D018515:Plant Leaves; D021241:Spectrometry, Mass, Electrospray Ionization; D013056:Spectrophotometry, Ultraviolet; D053719:Tandem Mass Spectrometry
chemical_list: D000975:Antioxidants; D010936:Plant Extracts; D002251:Carbon Tetrachloride
keywords: Ellagitannins; glutathione; lipid peroxidation; liver enzymes; superoxide dismutase