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Öğe Effects of Asphodeline lutea Compounds on Toxicity Models in Isolated Rat Microsomes and Hepatocytes(BENTHAM SCIENCE PUBL LTD, 2018) Kondeva-Burdina, Magdalena; Simeonova, Rumyana; Vitcheva, Vessela; Lazarova, Irina; Gevrenova, Reneta; Zheleva-Dimitrova, Dimitrina; Zengin, GökhanBackground: In the current study, we evaluate the possible in vitro hepatoprotective and antioxidant activity of Asphodeline lutea (L.) Rchb. dry root extract (ALE), and isolated from the same extract 2-acetyl-1,8-dimethoxy-3-methylnaphthalene (1). The potential of the main root compounds, chrysophanol (2) and caffeic acid (3), was studied as well. A model of non-enzyme lipid peroxidation (LPO) in isolated liver microsomes was induced by iron-ascorbic acid (Fe2+/AA) mixture and assessed by the quantity of malondialdehyde (MDA) -an LPO product. The incubation of the microsomes with ALE (1 mg/ml) and 1-3 (100 mu g/ml) resulted in a significant decrease in MDA production, compared to the Fe2+/AA incubated samples with 23% (ALE), 61 % (1), 62% (3), while classical hepatoprotector silymarin decreased the parameter with 64 %. Methods: Studied compounds showed some toxicity in isolated rat hepatocytes discerned by increased LDH leakage and MDA quantity, decreased cell viability and reduced glutathione (GSH) levels compared to the control (non-treated hepatocytes). Results: The antioxidant and hepatoprotective potential of 1-3 was observed in vitro against carbon tetrachloride (CCl4)-induced toxicity, where they normalize all the examined parameters pertur-bated by CCl4 administration. The effects of 1 are lower than 3 and silymarin, but were better than those of 2. Conclusion: On the basis of these results, we discuss a bidirectional potential of the assayed parameters that might be explained with naphthalene transformation in cytochrom P450-dependent oxidation by CYP3A. The lack of metabolism and bioactivation of CCl4 could explain the cytoprotective effects of 1-3. The pro-oxidant effects of 1 and 2, in in vitro models, could be due to naphthalene and anthraquinone bioactivation pathways involving toxic metabolites.Öğe Hepatoprotective and antioxidant potential of Asphodeline lutea (L.) Rchb. roots extract in experimental models in vitro/in vivo(ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER, 2016) Lazarova, Irina; Simeonova, Rumyana; Vitcheva, Vessela; Kondeva-Burdina, Magdalena; Gevrenova, Reneta; Zheleva-Dimitrova, Dimitrina; Zengin, GökhanThe aim of this study was to investigate the effect of Asphodeline lutea (L.) Rchb. dry root extract (ALE) administered alone and against carbon tetrachloride (CCl4)-induced liver injury in vitro/in vivo. The dried roots of A. lutea were extracted with 70% ethanol and was characterized with HPLC-UV. Hepatoprotective potential was investigated by in vivo/in vitro assays in Wistar rats as well as antioxidant properties. At concentrations ranging from 10 to 200 mg/mL of ALE significant cytotoxic effects on isolated hepatocytes were found. ALE showed some toxicity in Wistar rats discerned by increased ALT (Alanine transaminase), ALP (Alkaline phosphatase) activities and MDA (malondialdehyde) quantity, decreased GSH (reduced glutathione) levels without affecting the activity of the antioxidant enzymes (GPx (Gluthatione peroxidase), GR (Glutathione reductase) and GST (Glutathione-S-transferase activity)). The antioxidant and hepatoprotective potential of ALE was also observed in vitro/in vivo against CCl4-induced liver injury, where ALE normalizes all the examined parameters perturbated by CCl4 administration. In addition, ALE preserved the decreased cytochrome P450 level and EMND (Ethylmorphine-N-Demethylase) activity without affecting AH (Aniline 4-Hydroxylase) activity. ALE is rich in anthraquinones, naphthalenes and caffeic acid. The pro-oxidant effects of ALE could be due to naphthalene and anthraquinone bioactivation pathways involving toxic metabolites. (C) 2016 Elsevier Masson SAS. All rights reserved.