Pharmacotherapeutic potentials of astragalin against cisplatin-induced renal toxicity via regulating Nrf-2/keap-1 pathway

Arch Physiol Biochem. 2025 Dec;131(6):954-966. doi: 10.1080/13813455.2025.2508419. Epub 2025 May 26.

Abstract

Purpose: Cisplatin (CP) is a chemotherapeutic drug that can produce toxic effects in many organs of the body including kidney. Thus, the current trial was executed for 30 days to assess the alleviative effects of AST to avert CP instigated renal injuries.

Materials and methods: Forty-eight male albino rats were allocated into four groups including control, CP (10 mg/kg), CP+AST (10 mg/kg + 50mg/kg) and only AST (50 mg/kg). On the completion of trial, the rats were dissected and further analyses were performed.

Results: CP intoxication increased the expressions of pro-apoptotic markers (Caspase-3 and Bax) while reducing the expressions of Nrf-2 and antiapoptotic marker (Bcl-2) and lowering the expressions and activities of antioxidant enzymes i.e., GPx, GSR, CAT, HO-1, GST, SOD and GSH contents. Furthermore, CP intoxication elevated the levels of oxidative stress markers (MDA and ROS) and inflammatory markers (IL-6, IL-1 β, TNF-α, NF-kB and COX-2). CP exposure also disrupted the levels of renal function markers and renal histology. However, AST treatment ameliorated all the renal alterations induced by CP-exposure.

Conclusion: Therefore, AST protected the renal tissues from CP-instigated damages due to its antioxidant and reno-protective potential.

Keywords: Astragalin; antioxidants; cisplatin; inflammation; kidney damage.

MeSH terms

  • Acute Kidney Injury* / chemically induced
  • Acute Kidney Injury* / metabolism
  • Acute Kidney Injury* / pathology
  • Animals
  • Antineoplastic Agents* / adverse effects
  • Antineoplastic Agents* / toxicity
  • Antioxidants / pharmacology
  • Apoptosis / drug effects
  • Cisplatin* / adverse effects
  • Cisplatin* / toxicity
  • Kaempferols* / pharmacology
  • Kaempferols* / therapeutic use
  • Kelch-Like ECH-Associated Protein 1* / genetics
  • Kelch-Like ECH-Associated Protein 1* / metabolism
  • Kidney* / drug effects
  • Kidney* / metabolism
  • Kidney* / pathology
  • Male
  • NF-E2-Related Factor 2* / genetics
  • NF-E2-Related Factor 2* / metabolism
  • Oxidative Stress / drug effects
  • Rats
  • Signal Transduction / drug effects

Substances

  • Cisplatin
  • NF-E2-Related Factor 2
  • Nfe2l2 protein, rat
  • Kelch-Like ECH-Associated Protein 1
  • KEAP1 protein, rat
  • Kaempferols
  • Antioxidants
  • Antineoplastic Agents