Exploring the chondroitin sulfate nanogel's potential in combating nephrotoxicity induced by cisplatin and doxorubicin-An in-vivo study on rats

Int J Biol Macromol. 2024 Feb;258(Pt 1):128839. doi: 10.1016/j.ijbiomac.2023.128839. Epub 2023 Dec 20.

Abstract

In this study, we aim to unveil the potential of itaconyl chondroitin sulfate nanogel (ICSNG) in tackling chronic kidney diseases triggered by the administration of CDDP and doxorubicin (Adriamycin, ADR). To that end, the new drug delivery system (ICSNG) was initially prepared, characterized, and loaded with the target drugs. Thereafter, the in-vivo studies were performed using five equally divided groups of 100 male Sprague-Dawley (SD) rats. Biochemical evaluation and immunohistochemistry studies have revealed the renal toxicity and the ameliorative effects of ICSNG on renal function. When ICSNG-based treatments were contrasted with the CDDP and ADR infected groups, they significantly increased paraoxonase-1 (PON-1), superoxide dismutase (SOD), catalase (CAT) and albumin activity and significantly decreased nitric oxide (NO), tumor necrosis factor alpha (TNF-α), creatinine, urea, and cyclooxygenase-2 (COX-2) activity (p < 0.001). The findings of the current study imply that ICSNG may be able to lessen renal inflammation and damage in chronic kidney disorders brought on by the administration of CDDP and ADR. Interestingly, according to the estimated selectivity indices, the ICSNG-encapsulated drugs have demonstrated superior selectivity for cancer MCF-7 cells, over healthy HSF cells, in comparison to the bare drugs.

Keywords: Anti-inflammatory; Antioxidant; Chemotherapy nephrotoxicity; Cytotoxicity; Itaconyl chondroitin sulfate nanogel delivery system.

MeSH terms

  • Animals
  • Antioxidants / pharmacology
  • Chondroitin Sulfates / pharmacology
  • Cisplatin* / pharmacology
  • Creatinine / metabolism
  • Doxorubicin / pharmacology
  • Kidney*
  • Male
  • Nanogels
  • Oxidative Stress
  • Polyethylene Glycols*
  • Polyethyleneimine*
  • Rats
  • Rats, Sprague-Dawley

Substances

  • Cisplatin
  • Chondroitin Sulfates
  • polyethylene glycol polyethyleneimine nanogel
  • Nanogels
  • Antioxidants
  • Doxorubicin
  • Creatinine
  • Polyethylene Glycols
  • Polyethyleneimine