The Ameliorating Effect of Plasma Protein from Tachypleus tridentatus on Cyclophosphamide-Induced Acute Kidney Injury in Mice

Mar Drugs. 2019 Apr 15;17(4):227. doi: 10.3390/md17040227.

Abstract

In the study, the protective effect of plasma protein from Tachypleus tridentatus (PPTT) on acute kidney injury (AKI) and the related molecular mechanisms were first investigated by Western blotting analyses, TdT-mediated dUTP Nick-End Labeling (TUNEL) assay, and immunohistochemistry. It was found that PPTT had an obviously inhibitory effect on Reactive oxygen species (ROS) in cyclophosphamide (CTX)-exposed mice. Furthermore, results demonstrated that the renal cell death mode is due to inducing apoptosis and autophagy inhibited by dose-dependent PPTT in mice treated with CTX by decreasing the protein expression of bax, beclin-1, and LC3 and increasing the expression of bcl-2. Moreover, the p38 MAPK and PI3K/Akt signaling pathways were observed to take part in the PPTT-induced renal cell growth effect by enhancing the upregulation of the expression of Akt and p-Akt as well as the downregulation of the expression of p38 and p-p38, which indicated a PPTT ameliorating effect on AKI CTX-induced in mice through p38 MAPK and PI3K/Akt signaling pathways. Briefly, this article preliminarily studies the mechanism of the PPTT ameliorating effect on AKI CTX-induced in mice, which helps to provide a reference for PPTT clinical application in AKI therapy.

Keywords: Tachypleus tridentatus; apoptosis; autophagy; cyclophosphamide; kidney; plasma.

MeSH terms

  • Acute Kidney Injury / chemically induced
  • Acute Kidney Injury / drug therapy*
  • Acute Kidney Injury / metabolism
  • Acute Kidney Injury / pathology
  • Animals
  • Apoptosis / drug effects
  • Autophagy / drug effects
  • Beclin-1 / metabolism
  • Blood Proteins / isolation & purification
  • Blood Proteins / pharmacology*
  • Cyclophosphamide / pharmacology
  • Disease Models, Animal
  • Female
  • Horseshoe Crabs / chemistry*
  • Horseshoe Crabs / metabolism
  • Male
  • Mice
  • Microtubule-Associated Proteins / metabolism
  • Oxidative Stress / drug effects
  • Proto-Oncogene Proteins c-akt / metabolism
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Reactive Oxygen Species / antagonists & inhibitors
  • Reactive Oxygen Species / metabolism
  • Signal Transduction
  • Transcription Factor TFIIH
  • Transcription Factors / metabolism
  • bcl-2-Associated X Protein / metabolism
  • p38 Mitogen-Activated Protein Kinases / metabolism

Substances

  • Beclin-1
  • Becn1 protein, mouse
  • Blood Proteins
  • Gtf2h1 protein, mouse
  • Map1lc3b protein, mouse
  • Microtubule-Associated Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • Reactive Oxygen Species
  • Transcription Factors
  • bcl-2-Associated X Protein
  • Transcription Factor TFIIH
  • Cyclophosphamide
  • Proto-Oncogene Proteins c-akt
  • p38 Mitogen-Activated Protein Kinases