Effects of Asphodeline lutea Compounds on Toxicity Models in Isolated Rat Microsomes and Hepatocytes

Abstract

Background: 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 μg/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 perturbated 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. Keywords: Microsomes, hepatocytes, malondialdehyde, Asphodeline lutea (L.) Rchb., anthraquinones, naphthalenes.