Study on Cardiotoxicity and Mechanism of "Fuzi" Extracts Based on Metabonomics

Int J Mol Sci. 2018 Nov 7;19(11):3506. doi: 10.3390/ijms19113506.

Abstract

To investigate the toxicity of water and ethanol "Fuzi" (FZ) extracts and to explore the toxicity mechanism in rats. Water and ethanol extracts were prepared. Three groups of rats received the water extract, ethanol extract, or water by oral gavage for seven days. Pathological section staining of heart tissue. Colorimetric analysis was used to determine serum lactate dehydrogenase. The metabolic expression of small molecules in rats was measured by a metabolomics method. Western blotting was used to detect the expression of phosphoinositide 3-kinase (PI3K), protein kinase B (Akt), mammalian target of rapamycin (mTOR), transforming growth factor-β1 (TGF-β1), and caspase-3. Immunohistochemistry was used to detect the expression of CTnI, mTOR, and TGF-β1. The water and ethanol FZ extracts exert cardiotoxic effects via activating the PI3K/Akt/mTOR signaling pathway to induce cardiomyocyte apoptosis.

Keywords: Fuzi; PI3K/Akt/mTOR; cardiotoxicity; caspase-3; metabolomics.

MeSH terms

  • Animals
  • Apoptosis
  • Cardiotoxicity / blood
  • Cardiotoxicity / metabolism*
  • Cardiotoxicity / pathology
  • Caspase 3 / metabolism
  • Diterpenes
  • Drugs, Chinese Herbal
  • Ethanol
  • Male
  • Metabolome
  • Metabolomics*
  • Myocardium / metabolism
  • Myocardium / pathology
  • Myocytes, Cardiac / metabolism
  • Myocytes, Cardiac / pathology
  • Phosphatidylinositol 3-Kinase / metabolism
  • Plant Extracts / toxicity*
  • Proto-Oncogene Proteins c-akt / metabolism
  • Rats, Sprague-Dawley
  • Signal Transduction
  • TOR Serine-Threonine Kinases / metabolism
  • Transforming Growth Factor beta1 / metabolism
  • Troponin I / metabolism
  • Water

Substances

  • Diterpenes
  • Drugs, Chinese Herbal
  • Plant Extracts
  • Transforming Growth Factor beta1
  • Troponin I
  • fuzi drug herbal
  • Water
  • Ethanol
  • Phosphatidylinositol 3-Kinase
  • Proto-Oncogene Proteins c-akt
  • TOR Serine-Threonine Kinases
  • Caspase 3