Examining the quaternary ammonium chitosan Schiff base-ZnO nanocomposite's potential as protective therapy for rats' cisplatin-induced hepatotoxicity

Int J Biol Macromol. 2024 Sep;276(Pt 1):133616. doi: 10.1016/j.ijbiomac.2024.133616. Epub 2024 Jul 14.

Abstract

Background: Despite cisplatin's long history as a cornerstone in cancer therapy, both acquired chemoresistance and significant impacts on healthy tissues limit its use. Hepatotoxicity is one of its side effects. Adjunct therapies have shown promise in not only attenuating liver damage caused by cisplatin but also in enhancing the efficacy of chemotherapy. In this context, a new quaternary ammonium chitosan Schiff base (QACSB) was synthesized and applied as an encapsulating agent for the in-situ synthesis of QACSB-ZnO nanocomposite.

Material and methods: Thirty male albino rats were classified into Group 1 (control) distilled water, Group 2 (Cisplatin-treated) (12 mg/kg, i.p), and Group 3 (QACSB-ZnO NCs/cisplatin-treated) (150 mg/kg/day QACSB-ZnO NCs, i.p) for 14 days + a single dose of cisplatin. Liver functions, tissue TNF-α, MDA, and GSH were measured as well as histopathological and immunohistochemical studies were performed.

Results: The QACSB-ZnO NCs significantly restore liver functions, tissue TNF-α, MDA, and GSH levels (p < 0.001). Histopathological examination showed patchy necrosis in the cisplatin-treated group versus other groups. The QACSB-ZnO NCs showed a weak TGF-β1 (score = 4) and a moderate Bcl-2 immunohistochemistry expression (score = 6) versus the CP group.

Conclusions: QACSB-ZnO NCs have been shown to protect the liver from cisplatin-induced hepatotoxicity.

Keywords: Cisplatin hepatotoxicity, oxidative stress, and inflammation; Quaternary ammonium chitosan Schiff base; ZnO nanocomposites.

MeSH terms

  • Animals
  • Chemical and Drug Induced Liver Injury / drug therapy
  • Chemical and Drug Induced Liver Injury / metabolism
  • Chemical and Drug Induced Liver Injury / pathology
  • Chemical and Drug Induced Liver Injury / prevention & control
  • Chitosan* / chemistry
  • Chitosan* / pharmacology
  • Cisplatin* / adverse effects
  • Glutathione / metabolism
  • Liver / drug effects
  • Liver / metabolism
  • Liver / pathology
  • Male
  • Malondialdehyde / metabolism
  • Nanocomposites* / chemistry
  • Protective Agents / chemistry
  • Protective Agents / pharmacology
  • Quaternary Ammonium Compounds* / chemistry
  • Quaternary Ammonium Compounds* / pharmacology
  • Rats
  • Schiff Bases* / chemistry
  • Schiff Bases* / pharmacology
  • Tumor Necrosis Factor-alpha / metabolism
  • Zinc Oxide* / chemistry
  • Zinc Oxide* / pharmacology

Substances

  • Cisplatin
  • Schiff Bases
  • Chitosan
  • Quaternary Ammonium Compounds
  • Zinc Oxide
  • Glutathione
  • Protective Agents
  • Tumor Necrosis Factor-alpha
  • Malondialdehyde