Pracaxi oil affects xenobiotic metabolisms, cellular proliferation, and oxidative stress without cytotogenotoxic effects in HepG2/C3A cells

Toxicol In Vitro. 2022 Sep:83:105392. doi: 10.1016/j.tiv.2022.105392. Epub 2022 May 20.

Abstract

Pentaclethra macroloba (Willd.) Kuntze seeds oil has been used as a topical healing agent, applied mainly to parturients and snake bites. The objective was to investigate the effects of pracaxi oil (POP) on HepG2/C3A cells under cytogenotoxicity, cell cycle and apoptosis influence, and expression of metabolism and other related cell types proliferation genes. Cytotoxicity was analyzed by MTT test and apoptosis and cell cycle interferences by flow cytometry. To identify genotoxicity were used comet and micronucleus tests. RT-qPCR investigated gene expression. PO chemical characterization has shown two significant triterpenes, identified as oleanolic acid and hederagenin. The results showed that the PO did not reduce cell viability at concentrations ranging from 31 to 500 μg/ml. Comet and micronucleus assays revealed the absence of genotoxic effects, and flow cytometry showed no cell cycle or apoptosis disturbance. RT-qPCR indicated that PO up-regulated genes related to metabolism (CYP3A4, CYP1A2, CYP1A1), cell proliferation (mTOR), and oxidative stress (GPX1). The data indicate that PO has no cytogenotoxic effects and suggest that it activated the PI3/AKT/mTOR cascade of cell growth and proliferation. Inside the cells, the PO activated xenobiotic metabolizing genes, responsible for reactive oxygen species (ROS) generation, can neutralize ROS with increased GPX1 gene expression without genetic damage, interruption of the cell cycle, or induction of apoptosis.

Keywords: Cell proliferation; Comet assay; Gene expression of CYP; Micronucleus test; Pentaclethra macroloba seed oil; mTOR.

MeSH terms

  • Cell Proliferation
  • DNA Damage
  • Hep G2 Cells
  • Humans
  • Oxidative Stress*
  • Reactive Oxygen Species / metabolism
  • TOR Serine-Threonine Kinases / metabolism
  • Xenobiotics* / pharmacology

Substances

  • Reactive Oxygen Species
  • Xenobiotics
  • TOR Serine-Threonine Kinases