Astragaloside IV attenuates cadmium induced nephrotoxicity in rats by activating Nrf2

Sci Rep. 2025 Jan 15;15(1):2028. doi: 10.1038/s41598-025-86312-4.

Abstract

Acute kidney injury (AKI) has become a disease of global concern due to its high morbidity and mortality. This has highlighted the need for renoprotective agents. Astragaloside IV (AS-IV) is a saponin isolated from Astragalus membranaceus with good antioxidant, anti-inflammatory and anti-tumor properties. In this study, HK2 cells and rat model were utilized to explore the protective effect of AS-IV against cadmium chloride-induced oxidative stress-induced apoptosis. CdCl2-induced apoptosis, ROS production, and mitochondrial membrane potential alterations were significantly inhibited in AS-IV -treated HK2 cells. Expression of the mitochondria-associated apoptotic proteins Cleaved-Caspase3, Cleaved-Caspase9, and Cleaved-PARP was significantly reduced after AS-IV intervention. In addition, AS-IV inhibited Rat weight loss and also alleviated the symptoms of CdCl2-induced nephrotoxicity in a rat model of CdCl2-induced kidney injury. Further experiments showed that AS-IV suppresses heavy metal Cd-induced mitochondria-mediated apoptosis by regulating the Nrf2/HO-1 pathway. In conclusion, AS-IV could protect the kidney from heavy metal-induced toxicity and could be used as a nephroprotective agent.

Keywords: Astragaloside IV; Acute kidney injury; Apoptosis; Heavy metal cadmium; Oxidative stress.

MeSH terms

  • Acute Kidney Injury* / chemically induced
  • Acute Kidney Injury* / drug therapy
  • Acute Kidney Injury* / metabolism
  • Acute Kidney Injury* / pathology
  • Animals
  • Apoptosis* / drug effects
  • Cadmium Chloride / toxicity
  • Cadmium* / toxicity
  • Cell Line
  • Disease Models, Animal
  • Humans
  • Kidney / drug effects
  • Kidney / metabolism
  • Kidney / pathology
  • Male
  • Membrane Potential, Mitochondrial / drug effects
  • Mitochondria / drug effects
  • Mitochondria / metabolism
  • NF-E2-Related Factor 2* / metabolism
  • Oxidative Stress* / drug effects
  • Rats
  • Rats, Sprague-Dawley
  • Reactive Oxygen Species / metabolism
  • Saponins* / pharmacology
  • Signal Transduction / drug effects
  • Triterpenes* / pharmacology

Substances

  • Saponins
  • astragaloside A
  • Triterpenes
  • NF-E2-Related Factor 2
  • Cadmium
  • Nfe2l2 protein, rat
  • Reactive Oxygen Species
  • Cadmium Chloride