Hepatoprotective activity of Dodonaea viscosa leaf extract nanoparticles against N-nitrosodiethylamine induced tumor initiation in rat liver: Modulation of apoptosis and signaling pathways

Abstract

Aim: To evaluate the hepatoprotective activity of extract and silver nanoparticles of Dodonaea viscose leaves against hepatocellular carcinoma in male rats. Methodology: Eighty adult Wistar male rats were exposed to N-nitrosodiethylamine to induce hepatocellular carcinoma and allocated in different groups supplemented with 125, 250 and 500 mg kg-1 b.wt. of Dodonaea viscosa (DVLE) and DVLE-AgNPs for 12 weeks. Liver samples of treated groups were used to estimate the activities of alanine transaminase (ALT), aspartate aminotransferase (AST), glutathione peroxidase (GPx) and albumin levels. DNA damage, DNA adducts, ROS generation, apoptosis rate, and the expression analysis of the genes associated with the apoptosis (Bcls, Bax and p53) were also determined. Results: HCC group exhibited alterations in the activities of ALT, AST, GPx and levels of albumin compared with the control group. High rates of DNA damage, DNA adducts and ROS generations as well as changes in the apoptosis rates and the expression levels of Bcls, Bax and p53 genes were observed in HCC-induced rats compared with those in control group. DVLE and DVLE-AgNPs prevented the NDEA action on liver damage in a dose-dependent manner by reducing the alteration in the enzymatic and protein levels, decrease ROS generation, diminish genetic toxicity (DNA damage and DNA adducts), increased the apoptosis rate and suppressed the expression changes of Bcls, Bax and p53 genes. Interpretation: The action mechanism of DVLE and DVLE-AgNPs could probably attribute to the presence of polyphenolic and sesquiterpenes which are considered as potent inhibitors of cancer progression of liver cells.