Low dose pterostilbene-mediated hepatic chemoprevention in diethylnitrosamine-treated rats: Modulation of Ppar alpha, Nrf2 and Capase3 expression

Abstract

Background: Chronic liver disease (CLD) is a leading cause for liver cancer development. Pterostilbene (PTS) is a new promising natural agent with chemo- preventive effects. We hypothesized that low dose of PTS may have a hepato-protective role. This role may result from the cross talk between peroxisome-proliferator activated receptors alpha (Ppar alpha), nuclear factor erythroid 2-related factor 2 (Nrf2) and capase3 signaling pathways. Methods: We established diethyl nitrosamine (DENA) induced liver injury rat model then low dose of PTS was given by oral gavage for 16 weeks. We investigated serum liver function tests and hepatic levels of oxidative markers and alpha fetoprotein (AFP). Expression of Ppar alpha, Nrf2 and caspase3 by real-time quantitative polymerase chain reaction (qPCR) analysis were evaluated. Histopathological changes and immunohistochemistry for arginase-1 and glypican-3 reactivity were measured. Results: PTS significantly improved liver function tests and hepatic oxidative stress state and decreased hepatic glypican-3 and arginase-1 expression. Moreover, PTS significantly increased Ppar alpha, Nrf2 and caspase3 expression (p < 0.01). There was significant positive correlation between Ppar alpha, Nrf2 and caspase3 mRNA expression (r = 0.8) (p < 0.01). The damage of hepatocytes architecture was hampered with PTS in DENAtreated rats. In conclusion: PTS may be a promising natural hepatoprotective agent in the DENA-induced liver injury. This effect could be mediated through the interaction between Ppar alpha, Nrf2 and caspase3.