Trinitroglycerine-loaded chitosan nanoparticles attenuate renal ischemia-reperfusion injury by modulating oxidative

Zeinab Karimi1, Khatereh Asadi2,3,4, Pooran Ghahramani5

  • 1Shiraz Nephro-Urology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.

Scientific Reports
|December 31, 2024
PubMed

Insights

Trinitroglycerine combined with chitosan nanoparticles offers renoprotection against kidney injury. This TNG-CNP formulation improves antioxidant status and minimizes damage from ischemia-reperfusion injury.

Area of Science:

  • Nephrology
  • Pharmacology
  • Biomedical Engineering

Background:

  • Renal ischemia-reperfusion (I/R) injury is a significant cause of acute kidney injury (AKI).
  • Effective therapeutic strategies to mitigate I/R-induced AKI are clinically important.
  • Current treatments for AKI lack targeted delivery and optimal efficacy.

Purpose of the Study:

  • To investigate the renoprotective effects of a combination therapy using trinitroglycerine (TNG) encapsulated in chitosan nanoparticles (CNPs).
  • To evaluate the efficacy of TNG-CNPs in preventing renal damage and dysfunction caused by I/R injury in a rat model.
  • To assess the impact of TNG-CNPs on oxidative stress markers and kidney function post-I/R.

Main Methods:

  • Rats were subjected to bilateral renal pedicle occlusion for 60 minutes to induce I/R injury.
  • Animals were pretreated with TNG, CNPs, or a combination of TNG-CNPs via intraperitoneal injection 30 minutes before ischemia.
  • Kidney function was assessed by measuring plasma creatinine (Cr), blood urea nitrogen (BUN), and glomerular filtration rate (GFR).
  • Oxidative stress was evaluated by measuring total oxidative stress (TOS) and total antioxidative capacity (TAC).
  • Renal histopathology was examined using Hematoxylin and Eosin (H&E) staining.

Main Results:

  • Renal I/R injury led to elevated plasma Cr and BUN, decreased GFR, increased TOS, and reduced TAC.
  • Histopathological analysis showed significant kidney damage in the I/R group.
  • Pretreatment with TNG-CNPs significantly increased plasma and tissue TAC levels.
  • TNG-CNP treatment attenuated oxidative stress, improved renal function (reduced Cr and BUN, increased GFR), and corrected histopathological damage.

Conclusions:

  • The combination of trinitroglycerine with chitosan nanoparticles (TNG-CNPs) demonstrates significant renoprotective effects against ischemia-reperfusion-induced acute kidney injury.
  • TNG-CNPs enhance the kidney's antioxidant capacity and mitigate oxidative stress.
  • This novel formulation offers a promising therapeutic approach for preventing and treating renal I/R injury.

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