Zinc oxide nanoparticles regulate NF-kB expression and restrict inflammation response in doxorubicin-induced kidney injury in rats

Object Doxorubicin (DOX) is an anthracycline drug used for cancer treatment. However, its treatment is contiguous with renal toxic effects. This study aims to investigate the therapeutic effects of zinc oxide nanoparticles (ZnONPs) on doxorubicin-induced nephrotoxicity. Methods ZnONPs were prepared by the hydrothermal microwave method and characterized by XRD, SEM (combined with EDX) and HRTEM. To explore the possible nephrotoxicity and antioxidant effect of ZnONPs, rats were grouped as follows: control group, ZnONPs-treated group, doxorubicin group, and ZnONPs-Doxorubicin-treated group. Results DOX treatment increases renal tissue oxidative stress markers, while lowering antioxidant enzymes in tissue along with degenerative alterations in the renal tissue compared to control rats. Upon treatment with ZnONPs, a significant alteration was observed in the activities of superoxide dismutase, glutathione peroxidase, malondialdehyde, catalase, and the levels of kidney function, albumin, albuminuria, immune nuclear factor kappa B (NF-kB), and interleukin-6 (IL-6) compared to the doxorubicin group and control group. ZnONPs' administration to the doxorubicin group showed eminent renal injury control and restoration of the biochemical profile. This increases their active role in controlling kidney functions in order to improve nephrotoxicity and inflammatory responses. Histopathological and immunohistochemical observations provided context for these findings. In addition, ZnONPs alone did not show any undesirable effects on the renal parameters. However, its administration improves the renal functions. Conclusion We concluded that the administration of ZnONPs ameliorated nephrotoxicity in rats caused by doxorubicin through its antioxidant and anti-inflammatory and antiapoptotic properties. This shows the therapeutic application of ZnONPs as a safe anti-inflammatory and might serve as a potential adjuvant that avoids DOX-induced nephrotoxicity.