Ameliorative Effect of Eugenol-Loaded Chitosan Nanoparticles on Doxorubicin-Induced Nephrotoxicity in Rats

Introduction: Nephrotoxicity of chemotherapeutic agents remains a significant complication limiting the efficacy of the treatment. Doxorubicin (DOX) is a broad-spectrum anthracycline commonly utilized in the treatment of diverse malignancies, including leukemia, lymphomas, and solid tumors. DOX-induced nephrotoxicity results in heightened capillary permeability and glomerular atrophy. Eugenol has anesthetic, neuroprotective, antidiabetic, insecticidal, analgesic, and antifungal characteristics, rendering it a multifaceted natural molecule that aids in the prevention and treatment of different ailments. The current work intends to investigate the protective effects of eugenol-chitosan nanoparticles (EC NPs) against doxorubicin-induced nephrotoxicity. Methods: EC NPs were synthesized by ionic gelation methods and characterized using Fourier transform infrared spectroscopy, X-ray diffraction, and transmission electron microscopy. Nephrotoxicity was induced in rats by DOX injection (3 mg/kg body weight, i.p.) on days 2, 4, 6, 8, 10, and 12. There were five equal groups of forty rats: control, DOX, chitosan (60 mg/kg, body weight), eugenol (1 mg/kg, body weight), and EC NPs (60 mg/kg, body weight). The treatments were administered daily for 2 weeks. Results: A notable reduction was observed in the creatinine, urea, uric acid, microalbumin, sodium, calcium, phosphorus, malondialdehyde, nitric oxide, and DNA fragment concentrations, while glutathione levels reduced and catalase increased after EC NPs administration. EC NPs cause improvements in many histological sections of the kidney. Additionally, EC NPs inhibit caspase expression and stimulate Bcl-2 expression in the kidney. Discussion: The incorporation of eugenol with chitosan produces NPs that enhance the biological activities of eugenol, characterized by antioxidant and antiapoptotic effects, increased bioavailability, and the restoration of renal structure and function. Conclusion: The overall findings validated the protective efficacy of EC NPs against the nephrotoxic effects of DOX.