Sagittaria sagittifolia polysaccharide protects against six-heavy-metal-induced hepatic injury associated with the activation of Nrf2 pathway to regulate oxidative stress and apoptosis

J Inorg Biochem. 2022 Jul:232:111810. doi: 10.1016/j.jinorgbio.2022.111810. Epub 2022 Mar 28.

Abstract

The hepatic protective role of Sagittaria sagittifolia polysaccharide (SSP) and its possible mechanism were discussed in mice and L02 hepatocytes injured by heavy metals mixture of Cd + Cr (VI) + Pb + Mn + Zn + Cu. After 30-day intervention, blood and liver samples were collected for the relevant assessments. Methyl thiazolyl tetrazolium (MTT) assay showed 24 h was the best protecting point and the SSP protection at 1 mg/mL was strongest in L02 hepatocytes. SSP can alleviated hepatic injury, as evidenced by significantly decreased the activities of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and the malondialdehyde (MDA) content, also increased the superoxide dismutase (SOD) activity and glutathione (GSH), total sulphydryl (T-SH) contents. SSP effectively reduced pathological damage of mice and accumulation of heavy metals in liver, as well as decreased the level of reactive oxygen species (ROS) in L02 hepatocytes. After SSP treatment, the protein expressions or gene transcription of nuclear factor erythroid 2-related factor 2 (Nrf2), NAD(P)H dehydrogenase, quinone 1 (NQO1) and heme oxygenase1 (HO-1) decreased in L02. The protein expression of Nrf2 and NQO1 were increased while HO-1 was decreased in liver. Besides, SSP can attenuates apoptosis through reducing the protein expression of Bcl-2-associated X protein (Bax) and caspase-3, and increasing B-cell lymphoma gene 2 (Bcl-2) and B-cell lymphoma-extra large (Bcl-xl). SSP protects against six-heavy-metal-induced hepatic injury in mice and L02 hepatocytes. Supported by Nrf2 gene silencing, the mechanisms may correlate with activating Nrf2 pathway to mitigate oxidative stress and apoptosis.

Keywords: Hepatic injury; Multiple heavy metals; Nrf2; Oxidative stress; Sagittaria sagittifolia polysaccharide.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis
  • Glutathione / metabolism
  • Heme Oxygenase-1 / genetics
  • Heme Oxygenase-1 / metabolism
  • Heme Oxygenase-1 / pharmacology
  • Liver / metabolism
  • Lymphoma, B-Cell* / metabolism
  • Lymphoma, B-Cell* / pathology
  • Metals, Heavy* / metabolism
  • Metals, Heavy* / toxicity
  • NF-E2-Related Factor 2 / metabolism
  • Oxidative Stress
  • Polysaccharides / metabolism
  • Polysaccharides / pharmacology
  • Sagittaria* / metabolism
  • Signal Transduction

Substances

  • Metals, Heavy
  • NF-E2-Related Factor 2
  • Polysaccharides
  • Heme Oxygenase-1
  • Glutathione