Ameliorating Effect of Pentadecapeptide Derived from Cyclina sinensis on Cyclophosphamide-Induced Nephrotoxicity

Mar Drugs. 2020 Sep 9;18(9):462. doi: 10.3390/md18090462.

Abstract

Cyclophosphamide (CTX) is a widely used anticancer drug with severe nephrotoxicity. The pentadecapeptide (RVAPEEHPVEGRYLV) from Cyclina sinensis (SCSP) has been shown to affect immunity and to protect the liver. Hence, the purpose of this study was to investigate the ameliorating effect of SCSP on CTX-induced nephrotoxicity in mice. We injected male ICR mice with CTX (80 mg/kg·day) and measured the nephrotoxicity indices, levels of antioxidant enzymes, malondialdehyde (MDA), inflammatory factors, as well as the major proteins of the NF-κB and apoptotic pathways. Cyclophosphamide induced kidney injury; the levels of kidney-injury indicators and cytokines recovered remarkably in mice after receiving SCSP. The activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) increased, while there was a significant decrease in MDA levels. The kidney tissue damage induced by CTX was also repaired to a certain extent. In addition, SCSP significantly inhibited inflammatory factors and apoptosis by regulating the NF-κB and apoptotic pathways. Our study shows that SCSP has the potential to ameliorate CTX-induced nephrotoxicity and may be used as a therapeutic adjuvant to ameliorate CTX-induced nephrotoxicity.

Keywords: Cyclina sinensis; NF-κB pathway; apoptotic pathway; kidney nephrotoxicity; pentadecapeptide.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Anti-Inflammatory Agents / chemistry
  • Anti-Inflammatory Agents / isolation & purification
  • Anti-Inflammatory Agents / pharmacology*
  • Apoptosis / drug effects
  • Apoptosis Regulatory Proteins / metabolism
  • Bivalvia / metabolism*
  • Cyclophosphamide
  • Cytokines / metabolism
  • Disease Models, Animal
  • Inflammation Mediators / metabolism
  • Kidney / drug effects*
  • Kidney / metabolism
  • Kidney / pathology
  • Kidney Diseases / chemically induced
  • Kidney Diseases / drug therapy*
  • Kidney Diseases / metabolism
  • Kidney Diseases / pathology
  • Male
  • Malondialdehyde / metabolism
  • Mice, Inbred ICR
  • NF-kappa B / metabolism
  • Peptides / chemistry
  • Peptides / isolation & purification
  • Peptides / pharmacology*

Substances

  • Anti-Inflammatory Agents
  • Apoptosis Regulatory Proteins
  • Cytokines
  • Inflammation Mediators
  • NF-kappa B
  • Peptides
  • Malondialdehyde
  • Cyclophosphamide