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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.
Abstract:
Renal ischemia-reperfusion (I/R) injury is a common clinical factor for acute kidney injury (AKI). A current study investigated the renoprotective effects of the trinitroglycerine (TNG) combination with chitosan nanoparticles (CNPs) on renal I/R-induced AKI. Rats were randomly assigned to five groups (n = 8/group): Sham, I/R, TNG (50 mg/kg) + I/R, CNPs (60 mg/kg) + I/R, and TNG-CNPs + I/R. Bilateral renal pedicles were occluded for 60 min to induce ischemia. TNG, CNPs, or TNG-CNPs were administered intraperitoneally 30 min before renal ischemia. After 24 h of reperfusion, blood samples were collected, and both kidneys were removed. The left kidney was used for oxidative stress analysis. The right kidney was preserved in 10% formalin for histopathological examination via H&E staining. After renal ischemia-reperfusion injury, there was an observed increase in plasma creatinine (Cr) and blood urea nitrogen (BUN), accompanied by a decrease in glomerular filtration rate (GFR) in rats. Total oxidative stress (TOS) levels were also significantly higher in the I/R group, whereas total antioxidative capacity (TAC) was reduced. Histopathological examination revealed damage in the kidneys of rats in the I/R group. Pretreatment with the TNG-CNP formulation before I/R increased plasma and tissue TAC levels in rats. It also corrected the renal histopathological changes and functional disorders induced by I/R injury, as evidenced by reduced Cr and BUN, increased GFR, and attenuated oxidative stress. The results suggest that the TNG-CNP combination provides renoprotective effects against I/R-induced AKI by improving antioxidant status and minimizing renal injury.
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.

