Chemico-Biological Interactions 2014-04-01

Protective effects of neohesperidin dihydrochalcone against carbon tetrachloride-induced oxidative damage in vivo and in vitro.

Lihua Hu, Lingrui Li, Demei Xu, Xiaomin Xia, Ruxian Pi, Duo Xu, Wenchao Wang, Hong Du, Erqun Song, Yang Song

Index: Chem. Biol. Interact. 213 , 51-9, (2014)

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Abstract

The purpose of this study was to investigate the possible hepatoprotective effects of neohesperidin dihydrochalcone (NHDC) on carbon tetrachloride (CCl4)-induced acute oxidative injury in vivo and in vitro. In a mouse model, intraperitoneal injection of CCl4 resulted in a significant increase in serum aspartate transaminase (AST) and alanine transaminase (ALT) activities. Histopathological examination revealed severe hepatocyte necrosis and destruction of architecture in liver lesions, and immunohistochemical staining illustrated a remarkable enhancement of COX-2 and iNOS expression. The levels of hepatic antioxidant, such as, catalase (CAT), total superoxide dismutase (T-SOD), glutathione peroxidase (GP-X) and glutathione (GSH) were decreased, compared to the control group. However, pretreatment of NHDC for six consecutive days significantly ameliorated these changes. Moreover, Western blotting assay indicated pretreatment with NHDC also down-regulated CCl4-induced protein expressions of NF-_B, IL-6, caspase 3 and caspase 8. In HepG2 cell model, CCl4-treatment caused significant decrease in cell viability, antioxidant activities and GSH level, increase in intracellular reactive oxygen species (ROS) and thiobarbituric acid reactive substances (TBARS) level. Interestingly, pretreatment of NHDC effectively relieved CCl4-induced oxidative damage in a dose-dependent manner. In conclusion, NHDC appeared to possess promising anti-oxidative and anti-inflammatory capacities, it is possible to be used as a hepatoprotective agent.