Protective effect of Polygonatum sibiricum polysaccharides on gentamicin-induced acute kidney injury in rats via inhibiting p38 MAPK/ATF2 pathway

Int J Biol Macromol. 2020 May 15:151:595-601. doi: 10.1016/j.ijbiomac.2020.02.049. Epub 2020 Feb 10.

Abstract

The aim of this study was to investigate the protective effect of Polygonatum sibiricum polysaccharides (PSP) on acute kidney injury (AKI) in rats. The AKI model was established with 100 mg/kg of gentamicin (GM) intramuscularly. Six hours post-injection, rats were given intragastrically different dosages of PSP (0.25, 0.5, and 1 g/kg) for seven consecutive days. Results showed that compared with the model group, the kidney coefficient of rats decreased significantly (P < 0.05), and rat serum CRE and urea levels were significantly decreased (P < 0.05) in the PSP treatment group. The expression of NGAL, KIM-1, IL-1β, IL-6, TNF-α, and p38 MAPK mRNA in the kidney were significantly decreased (P < 0.05). The protein expression of p38 MAPK, p-p38 MAPK, and p-ATF2 were decreased to different degrees. Among the three-PSP treatment groups, the medium-dose group displayed the most protective effects. In conclusion, PSP had a powerful protective effect on GM-induced AKI in rats, it decreased the expression of NGAL or KIM-1 mRNA in kidney tissue and inhibited the p38 MAPK/ATF2 signaling pathway and the production of inflammatory factors TNF-α, IL-1β, and IL-6.

Keywords: Acute kidney injury; Gentamicin; Polygonatum sibircum polysaccharides; Rat; p38 MAPK/ATF2 pathway.

MeSH terms

  • Activating Transcription Factor 2 / metabolism*
  • Acute Kidney Injury / drug therapy
  • Acute Kidney Injury / etiology
  • Acute Kidney Injury / metabolism*
  • Acute Kidney Injury / pathology
  • Animals
  • Biomarkers
  • Biopsy
  • Blood Chemical Analysis
  • Disease Models, Animal
  • Gene Expression
  • Gentamicins / adverse effects
  • Kidney Function Tests
  • Male
  • Polygonatum / chemistry*
  • Polysaccharides / chemistry
  • Polysaccharides / isolation & purification
  • Polysaccharides / pharmacology*
  • Protective Agents / chemistry
  • Protective Agents / isolation & purification
  • Protective Agents / pharmacology*
  • Rats
  • Signal Transduction / drug effects*
  • p38 Mitogen-Activated Protein Kinases / metabolism*

Substances

  • Activating Transcription Factor 2
  • Atf2 protein, rat
  • Biomarkers
  • Gentamicins
  • Polysaccharides
  • Protective Agents
  • p38 Mitogen-Activated Protein Kinases