title: Prophylactic role of Enhydra fluctuans against arsenic-induced hepatotoxicity via anti-apoptotic and antioxidant mechanisms.
abstract: OBJECTIVE
  The present study was undertaken to evaluate the prophylactic effect of aqueous extract of Enhydra fluctuans (AEEF) against NaAsO2-induced hepatotoxicity.
  
  
  METHODS
  The cytoprotective effect of AEEF against NaAsO2 (10 µM) toxicity was measured on isolated murine hepatocytes. The effect on lipid peroxidation, protein carbonylation, cellular redox markers and signal proteins were measured after incubating the hepatocytes with NaAsO2 (10 µM) + AEEF (400 µg/ml). Finally, the prophylactic effect of AEEF (50 and 100 mg/kg) against NaAsO2 (10 mg/kg) toxicity was measured by in vivo assay in experimental mice.
  
  
  RESULTS
  In vitro bioassay on isolated mouse hepatocytes confirmed cytoprotective effect of AEEF. The NaAsO2 treatment significantly (P<0.01) increased the levels of lipid peroxidation, protein carbonylation with concomitant reduction (P<0.01) of antioxidant enzymes and reduced glutathione levels in hepatocytes. In addition, NaAsO2 significantly (P<0.05-0.01) altered the expression of intrinsic (Bad↑, Bcl-2↓, cleaved-caspase 3↑ and cleaved-caspase 9↑) and extrinsic (Fas↑, Bid↑, cleaved-caspase 8↑) transcription proteins participating in the apoptotic event. However, AEEF treatment could significantly rescue the aforementioned parameters near-normal levels. In in vivo bioassay, NaAsO2 intoxication increased (p<0.01) bioaccumulation of As along with the abnormalities in haematological parameters and redox imbalance in the livers of experimental mice. Treatment with AEEF, however, could significantly (P<0.05-0.01) restore the hematological and redox parameters to the near-normal levels, with histological studies of livers supporting the protective role of AEEF.
  
  
  CONCLUSIONS
  Presence of substantial quantity of ascorbic acid, phenolics and flavonoids in the extract may be responsible for overall protective effect.
authors.affiliation: a Advanced Pharmacognosy Research Laboratory, Department of Pharmaceutical Technology , Jadavpur University , Kolkata 700032 , India.
authors.forename: Tarun K
authors.initials: TK
authors.lastname: Dua
authors.affiliation: a Advanced Pharmacognosy Research Laboratory, Department of Pharmaceutical Technology , Jadavpur University , Kolkata 700032 , India.
authors.forename: Saikat
authors.initials: S
authors.lastname: Dewanjee
authors.affiliation: a Advanced Pharmacognosy Research Laboratory, Department of Pharmaceutical Technology , Jadavpur University , Kolkata 700032 , India.
authors.forename: Ritu
authors.initials: R
authors.lastname: Khanra
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D017209:Apoptosis / Q000187:drug effects; D001151:Arsenic / Q000633:toxicity*; D019659:Asteraceae / Q000737:chemistry*; D001681:Biological Assay; D022781:Hepatocytes / Q000187:drug effects*; D015227:Lipid Peroxidation / Q000187:drug effects; D051379:Mice; D018384:Oxidative Stress / Q000187:drug effects; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D050050:Protein Carbonylation / Q000187:drug effects
chemical_list: D000975:Antioxidants; D010936:Plant Extracts; D001151:Arsenic
keywords: Apoptosis; Arsenic toxicity; Enhydra fluctuans; NaAsO2; Oxidative stress