Protective effects of schizandrin and schizandrin B towards cisplatin nephrotoxicity in vitro

J Appl Toxicol. 2014 Dec;34(12):1311-9. doi: 10.1002/jat.2951. Epub 2013 Oct 24.

Abstract

Renal proximal tubular epithelial cells are the main targets of toxic drugs such as cisplatin (CisPt), an alkylating agent indicated for the treatment of solid organ tumors. Current techniques aiming at reducing nephrotoxicity in patients receiving CisPt are still not satisfactory as they can only partially prevent acute kidney injury. New nephroprotective strategies remain to be developed. In the present in vitro study, schizandrin (Schi) and schizandrin B (Schi B), major phytochemicals from Schisandra chinensis (Turcz.) Baill. fruits, were tested on HK-2 cells along four processes that could help alleviate CisPt toxicity. Results indicated that: (i) both Schi and Schi B enhanced cell survival via reducing apoptosis rate; (ii) only Schi showed moderate effects towards modulation of regeneration capacities of healthy cells; (iii) both Schi and Schi B limited extracellular matrix deposition; and (iv) both compounds could help preventing dedifferentiation processes via the β-catenin pathway. Schi and Schi B present promising activities for future development of protective agents against CisPt nephrotoxicity.

Keywords: Apoptosis; Cisplatin; HK-2 cells; Regeneration; Schizandrin; Schizandrin B; β-catenin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / toxicity*
  • Cell Culture Techniques
  • Cell Cycle / drug effects
  • Cell Line
  • Cell Survival / drug effects
  • Cisplatin / toxicity*
  • Collagen / biosynthesis
  • Cyclooctanes / isolation & purification
  • Cyclooctanes / pharmacology*
  • Epithelial Cells / drug effects
  • Epithelial Cells / pathology
  • Fruit / chemistry
  • Humans
  • Kidney Tubules, Proximal / drug effects*
  • Kidney Tubules, Proximal / pathology
  • Lignans / isolation & purification
  • Lignans / pharmacology*
  • Molecular Structure
  • Polycyclic Compounds / isolation & purification
  • Polycyclic Compounds / pharmacology*
  • Protective Agents / isolation & purification
  • Protective Agents / pharmacology*
  • Schisandra / chemistry

Substances

  • Antineoplastic Agents
  • Cyclooctanes
  • Lignans
  • Polycyclic Compounds
  • Protective Agents
  • schizandrin B
  • Collagen
  • schizandrin
  • Cisplatin