The encapsulation ofellagic acid increases its hepatoprotective potential in cyclophosphamide induced liver injury model

Introduction: Encapsulation and controlled release of compounds from nanoliposomesis rapidly developing strategy for increasingtheir solubility and enable compounds to reach target tissue [1]. Ellagic acid is a naturally occurring polyphenol, with strong antioxidant potential, that can be found in numerous plants including fruit and nuts [2]. In this study we aimed to evaluate whether the encapsulation of ellagic acid into nanoliposomes would improve its potential in preventing cyclophosphamide-induced liver damage. Methods: Experiments were performed on 60 male Wistar rats divided into ten groups of 6 animals, treated daily by an intraperitoneal injection. CP-group received cyclophosphamidein a single dose (200 mg/kg) on the third day; other experimental groups received the same dose of cyclophosphamide and: corn oil (0.2 ml/day) (OCP-group), empty nanoliposomes (10 ml/kg) (NLCP-group), ellagic acid (10 mg/kg) (EACP-group) and encapsulated ellagic acid (10 mg/kg) (EANLCP-group), for 5 days. The remaining five groups served as controls and received for 5 days: saline (0.2 ml/day)(C-group),corn oil (0.2 ml/day) (O-group), empty nanoliposomes (10 ml/kg) (NL-group), ellagic acid (10 mg/kg) (EA-group) and encapsulated ellagic acid (10 mg/kg) (EANL-group). Quantitative evaluation of structural and functional changes of liver was performed by histopathological and biochemical serum analyses and determination of oxidative stress parameters. Results: Cyclophosphamide induced severe functional and morphological alterations of liver with disarrangement of hepatic plates caused by vacuolar degeneration and focal apoptosis. Histological damage was most pronounced in periportal areas(Figure 1F).Pathohistological findings were followed by AST, ALP, γ-GT and ALT increase and disturbances of tissue antioxidant status. Application of both forms of ellagic acid ameliorated changes of serum and oxidative damage markers and markedly reversed structural changes of liver tissue induced by cyclophosphamide. Animals that received nanoliposome-encapsulated ellagic acid showed higher degree of recovery then those treated with free form (Figure 1). Discussion: Encapsulated ellagic acid was shown to possess stronger antioxidant activity which could be possibly related to its higher stability in nanoliposomes which might prolong the presence of ellagic acid in circulationand could significantly increase its hepatoprotective potential [3].

Author(s): Sonja IliÄ

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