Nrf2 modulates cell proliferation and antioxidants defenses during liver regeneration induced by partial hepatectomy

Nrf2 调节部分肝切除术诱导的肝再生过程中的细胞增殖和抗氧化剂防御

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作者:Ángel Morales-González, Mirandeli Bautista, Eduardo Madrigal-Santillán, Araceli Posadas-Mondragón, Liliana Anguiano-Robledo, Eduardo Madrigal-Bujaidar, Isela Álvarez-González, Tomás Fregoso-Aguilar, Evila Gayosso-Islas, Cecilia Sánchez-Moreno, José A Morales-González

Abstract

The objective was to determine the regulatory dynamic of Nrf2 during liver regeneration and the administration of EtOH and/or the G. schiedeanum extract. Male Wistar rats weighing 200-230 g were subjected to a 70% partial hepatectomy; they were then divided into three groups (groups 1-3). During the experiment, animals in Group 1 drank only water. The other two groups (2-3) received an intragastric dose of ethanol (1.5 g/kg BW, solution at 40% in isotonic saline solution). Additionally, rats in group 3 received a geranium extract daily at a dose of 300 mg/kg BW i.g. EtOh and/or Geranium schiedeanum was administered to rats with regenerating livers for 7 days. At the end of treatment, the activity was determined of the antioxidant enzymes, DNA concentration, TBARS, and TAC, in addition to the expression of Nrf-2, Cyclin D1, and Nqo1. EtOH increased ROS and Nrf-2, which activated the antioxidant defenses and delayed liver proliferation. On the other hand, Geranium schiedeanum exerted an antioxidant effect, diminishing ROS, but Nrf-2 expression increased, favoring liver proliferation through the increase of DNA concentration and the overexpression of Cyclin D1, however it did not activate the antioxidant defenses. In sum, it can be concluded that Nrf-2 possesses a regulatory dynamic that is evident in the presence of a toxic agent (EtOH) and/or a phytochemical agent with antioxidant capacity (Geranium schiedeanum) during liver regeneration.

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