Piperazine ferulate attenuates gentamicin-induced acute kidney injury via the NF-κB/NLRP3 pathway

Dan Li1, Bo Li2, Yixin Rui1

  • 1State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan 611137, China; School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan 611137, China.

Abstract

Insights

Piperazine ferulate (PF) protects against acute kidney injury (AKI) by reducing inflammation. This study shows PF inhibits the NF-κB/NLRP3 pathway, offering a potential therapeutic strategy for kidney inflammation.

Area of Science:

  • Nephrology
  • Pharmacology
  • Inflammation Research

Background:

  • Piperazine ferulate (PF) is clinically used for chronic nephritis and nephrotic syndrome, known to reduce inflammation via nuclear factor kappa-B (NF-κB) signaling.
  • Acute kidney injury (AKI) involves renal inflammation, but PF's protective effects and mechanisms in AKI remain unclear.

Purpose of the Study:

  • To investigate the nephroprotective effects of Piperazine ferulate (PF) in a rat model of gentamicin (GM)-induced acute kidney injury (AKI).
  • To elucidate the underlying anti-inflammatory mechanisms of PF in AKI.

Main Methods:

  • Male Sprague Dawley rats received gentamicin (GM) with or without PF (50, 100 mg/kg) for 7 days.
  • In vitro, NRK-52e cells were exposed to GM with or without PF treatment.
  • Renal and cellular injury, alongside inflammatory markers, were assessed.

Main Results:

  • PF treatment significantly improved renal function and reduced pathological damage and inflammation in GM-induced AKI rats.
  • PF mitigated cell damage and inflammatory responses in vitro.
  • Mechanistically, PF inhibited NF-κB and NLRP3 inflammasome activation, downregulating key inflammatory proteins and genes (p-IKKα/β, p-p65, p65, p50, p105, NLRP3, IL-1β).

Conclusions:

  • Piperazine ferulate (PF) demonstrates significant nephroprotective effects against acute kidney injury (AKI).
  • PF exerts its protective effects by inhibiting the NF-κB/NLRP3 inflammatory pathway.
  • PF represents a potential therapeutic agent for mitigating inflammation-associated AKI.