Protective effects of cyclic helix B peptide on aristolochic acid induced acute kidney injury

Biomed Pharmacother. 2017 Oct:94:1167-1175. doi: 10.1016/j.biopha.2017.07.131. Epub 2017 Aug 17.

Abstract

Background: Aristolochic acid (AA) injuries remain a serious condition associated with acute renal dysfunction. Herein, the effect and mechanism of a novel tissue protective peptide, cyclic helical B-peptide (CHBP) derived from erythropoietin, were investigated in a mice model.

Methods: Mice were randomly divided into four groups, receiving the following treatments (1: saline; 2: AA 10mg/kg; 3: AA 10mg/kg +CHBP 4nmol/kg; 4: AA 10mg/kg +CHBP 8nmol/kg).

Results: Blood urea nitrogen and serum creatinine was increased by AA but decreased by CHBP in a dose-dependent fashion. CHBP also significantly improved renal tubular injury and inflammatory infiltration, which was gradually increased by AA. Apoptotic cells, infiltrating inflammatory cells, and active caspase-3+ cells were greatly reduced by CHBP. In addition, CHBP inhibited caspase-3, 9 and improved bcl-2, bcl-xl protein expression in vivo.

Conclusion: Taken together, we demonstrated, for the first time, that CHBP effectively improved renal function and tissue damage caused by AA, which maybe through reducing caspase-3 activation, apoptosis, and inflammation.

Keywords: Acute kidney injury; Aristolochic acid; Cyclic Helix B peptide.

MeSH terms

  • Acute Kidney Injury / chemically induced*
  • Acute Kidney Injury / drug therapy*
  • Acute Kidney Injury / metabolism
  • Animals
  • Aristolochic Acids / pharmacology*
  • Blood Urea Nitrogen
  • Caspase 3 / metabolism
  • Caspase 9 / metabolism
  • Creatinine / metabolism
  • Disease Models, Animal
  • Enkephalins / pharmacology*
  • Inflammation / drug therapy
  • Inflammation / metabolism
  • Kidney / drug effects
  • Kidney / metabolism
  • Kidney Function Tests / methods
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Protective Agents / pharmacology*
  • Protein Precursors / pharmacology*
  • Reperfusion Injury / drug therapy
  • Reperfusion Injury / metabolism
  • bcl-X Protein / metabolism

Substances

  • Aristolochic Acids
  • Enkephalins
  • Protective Agents
  • Protein Precursors
  • bcl-X Protein
  • peptide B
  • Creatinine
  • Caspase 3
  • Caspase 9