Piceatannol Mediated Modulation of Oxidative Stress and Regeneration in the Liver of Endotoxemic Mice

Abstract

Liver plays a pivotal role in host defense mechanisms related to endotoxemia. However, liver dysfunction often occurs in early sepsis. This study investigated the hepatoprotective potential of natural stilbenoid piceatannol (PIC) in lipopolysaccharide (LPS)-induced endotoxemic mice. Swiss Albino mice were divided into four groups: Control (C), LPS administrated (LPS), PIC administrated (PIC), and LPS administrated/PIC preadministrated (LPS+PIC) animals. PIC was administrated intraperitoneally (i.p.) at the dose of 4 mg/kg/day during 7 days. Endotoxemia was induced with a single i.p. administration of LPS at the dose of 4 mg/kg. Superoxide dismutase (SOD), catalase (CAT) and lipid peroxidation (LP) levels, light microscopic pathology, and genotoxicity were investigated. Proliferating cell nuclear antigen and SQSTM1/p62 immunofluorescence were measured. PIC preadministration restored SOD activity, reduced LP and genotoxicity. However, moderate level of oxidative stress (OS) had been progressed in PIC preadministrated animals depending upon prolonged autophagic response and selective degradation of CAT. Positive OS stimulated liver regeneration by upregulating oval cells' and downregulating hepatocytes' proliferation and resulted in the maintanence of hepatic tissue integrity in PIC preadministrated animals. These results suggested that PIC may be a useful hepatoprotective agent in LPS-induced endotoxemia as a modulator of OS and genotoxicity, as an inducer of autophagy, and as a promoter of liver regeneration.