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

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.

Keywords: Liver regeneration; Nrf-2; ethanol; free radicals; geranium schiedeanum.

Figure 1

Representative-band DNA and DNA concentrations in each experimental group after 7 days of treatment with PH, EtOH, and the Geranium schiedeanum (Gs) extract. PH: Partial Hepatectomy; EtOH: Ethanol; Gs: Geranium schiedeanum.

Figure 2

Catalase (CAT) (A) and Superoxide dismutase (SOD) (B) activity in the distinct study groups. Values are expressed as mean ± Standard Error of the Mean (SEM) in each experimental group (n = 5-6). aP<0.05 vs the control group; bP<0.05 vs the PH group; cP<0.05 vs the PH-Gs-EtOH group. PH: Partial Hepatectomy; EtOH: Ethanol; Gs: Geranium schiedeanum.

Figure 3

Gluthathione peroxidase (GPx) (A) and glutathione reductase (GR) (B) activity in the distinct study groups. Values are expressed as mean ± Standard Error of the Mean (SEM) in each experimental group; (n = 5-6). aP<0.05 vs the control group; bP<0.05 vs the PH group; cP<0.05 vs the PH-Gs-EtOH group. PH: Partial Hepatectomy; EtOH: Ethanol; Gs: Geranium schiedeanum.

Figure 4

Representative-band protein of Nrf2, Nqo1, CD1, and β-actin tested by Western blotting (upper panel) and its quantification by scanning densitometry (lower panel). Values are expressed as the percentage ± Standard Error of the Mean (SEM) in each experimental group (n = 3). aP<0.05 vs the control group; bP<0.05 vs the PH group; cP<0.05 vs the PH-Gs-EtOH group. PH: Partial Hepatectomy; EtOH: Ethanol; Gs: Geranium schiedeanum.