title: Protective effect of Terminalia muelleri against carbon tetrachloride-induced hepato and nephro-toxicity in mice and characterization of its bioactive constituents.
abstract: BACKGROUND
  Terminalia is used in folk medicine for the treatment of various diseases.
  
  
  OBJECTIVE
  The objective of this study is to investigate the hepatonephro protective activity of a polyphenol-rich fraction (TMEF) obtained from Terminalia muelleri Benth. (Combretaceae) against CCl4-induced toxicity in mice.
  
  
  METHODS
  TMEF was administered (100, 200, and 400 mg/kg/d) for 5 d. CCl4 was administered at the end of the experiment. Hepatic and renal biomarkers were measured in the serum. Glutathione (GSH), superoxide dismutase (SOD), and malondialdehyde (MDA) were estimated in the liver and kidney tissues. The active constituents of TMEF were identified by HPLC-PDA-ESI/MS/MS.
  
  
  RESULTS
  TMEF is rich in ellagitannins, galloyl esters, phenolic acids, and flavone-C-glucosides. TMEF pretreatment significantly (p < 0.001) inhibited the CCl4-induced increase in ALT (17, 43, and 53%), AST (20, 46, and 58%), ALP (20, 48, and 56%), LDH (21, 47, and 58%), hepatic MDA (23, 49, and 54%), renal MDA (22, 35, and 52%), creatinine (48, 66, and 91%), uric acid (16, 34, and 59%), urea (22, 39, and 59%), and cholesterol (20, 27, and 46%). Furthermore, TMEF administration significantly (p < 0.001) increased hepatic GSH (15, 51, and 79%), renal GSH (23, 45, and 73%), hepatic SOD (9, 52, and 95%), renal SOD (39, 66, and 85%) and protein levels (17, 24, and 29%) at the tested doses of TMEF, respectively. Pretreatment with TMEF preserved the hepatic architecture and protected from ballooning degeneration, liver necrosis, renal inflammation, and degeneration of the kidney tubules.
  
  
  CONCLUSIONS
  TMEF has a marked hepato-nephro protective effect.
authors.affiliation: a Department of Pharmacognosy , Faculty of Pharmacy, Ain-Shams University , Cairo , Egypt .
authors.forename: Nouran Mohamed
authors.initials: NM
authors.lastname: Fahmy
authors.affiliation: a Department of Pharmacognosy , Faculty of Pharmacy, Ain-Shams University , Cairo , Egypt .
authors.forename: Eman
authors.initials: E
authors.lastname: Al-Sayed
authors.affiliation: b Department of Pharmacology , Faculty of Veterinary Medicine, Suez Canal University , Ismailia , Egypt , and.
authors.forename: Mohamed M
authors.initials: MM
authors.lastname: Abdel-Daim
authors.affiliation: c Laboratory of Organic Chemistry and Chemical Biology, Department of Chemistry , University of Turku , Turku , Finland.
authors.forename: Maarit
authors.initials: M
authors.lastname: Karonen
authors.affiliation: a Department of Pharmacognosy , Faculty of Pharmacy, Ain-Shams University , Cairo , Egypt .
authors.forename: Abdel Nasser
authors.initials: AN
authors.lastname: Singab
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D002251:Carbon Tetrachloride / Q000633:toxicity; D056486:Chemical and Drug Induced Liver Injury / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D004305:Dose-Response Relationship, Drug; D007677:Kidney Function Tests; D007684:Kidney Tubules / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008111:Liver Function Tests; D008297:Male; D051379:Mice; D015394:Molecular Structure; D009393:Nephritis / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D010936:Plant Extracts / Q000302:isolation & purification / Q000627:therapeutic use* / Q000633:toxicity; D018515:Plant Leaves / Q000737:chemistry; D059808:Polyphenols / Q000302:isolation & purification / Q000627:therapeutic use* / Q000633:toxicity; D020011:Protective Agents / Q000302:isolation & purification / Q000627:therapeutic use* / Q000633:toxicity; D029766:Terminalia / Q000737:chemistry*; D023382:Toxicity Tests, Acute
chemical_list: D000975:Antioxidants; D010936:Plant Extracts; D059808:Polyphenols; D020011:Protective Agents; D002251:Carbon Tetrachloride
keywords: Antioxidant; ellagitannins; flavone-C-glucosides; glutathione; hepatoprotective; lipid peroxidation; nephroprotective