title: Geraniin and amariin, ellagitannins from Phyllanthus amarus, protect liver cells against ethanol induced cytotoxicity.
abstract: Ethanol mediated free radical generation plays an important role in the pathogenesis of liver injuries and alcoholic liver diseases. In the present study two ellagitannins namely geraniin and amariin isolated from Phyllanthus amarus were examined for their ability to protect mouse liver slices against ethanol induced toxicity and possible mechanism of its protection. Oxidative stress markers such as, lipid peroxidation, protein carbonyl formation, amount of 8-hydroxy-2-deoxyguanosine and antioxidant enzymes levels were measured using specific biochemical assays. Poly (ADP-ribose) polymerase (PARP), Bax and Bcl2 were checked to assess the induction of apoptosis using western blots. The results showed that geraniin and amariin protected mouse liver slices against ethanol induced cytotoxicity. Both compounds inhibited oxidation of lipid, protein and formation of 8-hydroxy-2-deoxyguanosine, all of which were found to be elevated on exposure to ethanol. These compounds restored the antioxidant enzymes altered on ethanol exposure. Compounds also inhibited the cleavage of PARP and bax and restored Bcl2, induced on exposure to ethanol. In summary, both ellagitannins effectively protected mouse liver slices against ethanol induced cytotoxicity and apoptosis by reducing oxidative damage to biological molecules and modulating Bax/Bcl-2 ratio respectively, thus minimizing liver injury.
authors.affiliation: Department of Zoology, University of Pune, Pune 411 007, India.
authors.forename: Jayant S
authors.initials: JS
authors.lastname: Londhe
authors.forename: Thomas P A
authors.initials: TP
authors.lastname: Devasagayam
authors.forename: L Yeap
authors.initials: LY
authors.lastname: Foo
authors.forename: Padma
authors.initials: P
authors.lastname: Shastry
authors.forename: Saroj S
authors.initials: SS
authors.lastname: Ghaskadbi
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D000431:Ethanol / Q000737:chemistry / Q000633:toxicity*; D005786:Gene Expression Regulation / Q000187:drug effects; D005960:Glucosides / Q000737:chemistry / Q000494:pharmacology*; D022781:Hepatocytes / Q000187:drug effects*; D047348:Hydrolyzable Tannins / Q000737:chemistry / Q000494:pharmacology*; D051379:Mice; D010084:Oxidation-Reduction; D029803:Phyllanthus / Q000737:chemistry*; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases / Q000235:genetics / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D000975:Antioxidants; C494827:Bax protein, mouse; D005960:Glucosides; D047348:Hydrolyzable Tannins; D019253:Proto-Oncogene Proteins c-bcl-2; C581165:amariin; D051028:bcl-2-Associated X Protein; D000431:Ethanol; C024603:Geraniin; C499321:Parp1 protein, mouse; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases