Trinitroglycerine-loaded Chitosan Nanoparticles Attenuate Renal Ischemia- Reperfusion Injury by Modulating Oxidative Stress

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Abstract

Background: 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. Methods: 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 minutes to induce ischemia. TNG, CNPs, or TNG-CNPs were administered intraperitoneally 30 minutes before renal ischemia. After 24 hours 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. Result: After renal I/R injury, plasma creatinine (Cr), blood urea nitrogen (BUN), and glomerular filtration rate (GFR) significantly increased 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. Conclusion: The results suggest that the TNG-CNP combination provides renoprotective effects against I/R-induced AKI by improving antioxidant status and minimizing renal injury.

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