engleski

Olive oil polyphenols induce protective hormetic response and enhance liver mass restoration after injury

Polyphenols may act as hormetic effectors which affect stress responsive gene signatures under the control of Nrf2. This transcription factor is indispensable for successful cell cycle progression and induction of battery cytoprotective genes associated with the control of a process of liver self-repair, known as the liver regeneration (LR). We tested the possibility to affect liver repair response induced by 1/3 hepatectomy (pH) in mice through the pre-exposure to olive oil polyphenols extract (PFE) by targeting Nrf2 pathway. Prior to pH mice were administered PFE or saline during seven consecutive days, while controls received vehicle alone. Hepatic mRNA level of Nrf2, γ-glutamylcystein synthetase (GCS) and heme oxygenase (HO-1) along with glutathione, lipid peroxidation (LP) and serum α-glutathione S-transferase (GSTα) level was determined at different time intervals after pH. Calculated relative liver weight was used to assess the liver mass restoration. Pre-treatment with PFE increased LP and GSTα level and promoted glutathione depletion within the first three hours after pH, pointing to the increase in oxidant and electrophilic load. These changes were accompanied by the adaptive stress response induction, as indicated by the Nrf2, HO-1 and GCS gene upregulation, leading to the normalization of parameters of oxidative stress, reduced detoxification demands and recovery of glutathione status, with the final outcome in increased liver mass recovery. Pre-exposure to PFE increases overall metabolic load which could play a role in the development of LR by sensitizing cells to acquire proliferative competence through the induction of stress response gene-profiles under the control of Nrf2.

Nrf2, γ-glutamylcystein synthetase, heme oxygenase (HO-1), α-glutathione S-transferase , polyphenols, hepatectomy

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