Green-synthesized Vachellia sieberiana-Zinc oxide nanoparticles suppress inflammation and oxidative DNA damage in premalignant colon

Introduction: Nanoparticles synthesised using plant bioactive compounds for biomedical applications are gaining momentum. Green-fabricated zinc oxide nanoparticles using aqueous Vachellia sieberiana aerial-part extract (V. sieberiana-ZnONPs) were employed for this study. Materials and methods: The synthesised V. sieberiana-ZnONPs were characterised using UV-Visible spectrophotometry (UV–Vis), Fourier-Transform Infrared (FTIR), X-ray diffraction (XRD), and Thermogravimetric analysis (TGA). Male Wistar rats were exposed to 1,2-dimethylhydrazine/dextran sodium sulphate (DMH/DSS) subcutaneously once per week and 3% DSS via their drinking water. The animals were orally administered 100, 200, and 400 mg/kg body weight (b.w.) of V. sieberiana-ZnONPs and doxorubicin (2 mg/kg b.w. per week) intraperitoneally for five weeks. Colon inflammation (Tumour necrosis factor-alpha (TNF-α), Interleukin-1beta (IL-1β)), oxidative status (reduced glutathione (GSH), superoxide dismutase (SOD), Glutathione peroxidase (GPx), Glutathione-S-transferase (GST), and Thiobarbituric acid reactive substances (TBARS)), apoptosis (DNA fragmentation), DNA damage (8-hydroxy-2’-deoxyguanosine (8-OHdG)), colon aberrant crypt foci (ACF) and histological architectures were assessed. The data were analysed using a one-way ANOVA, followed by a post hoc Tukey test. Results: Characterisation analyses revealed the synthesis of thermally stable crystalline hexagonal wurtzite ZnO nanoparticles. The nanoparticles significantly ameliorated DMH/DSS-induced TNF-α (43.89%), IL-1β (8.39%), TBARS (414.13%), and 8-OHdG (18.94%). The V. sieberiana-ZnONPs mitigated DMH/DSS-induced GSH, GPx, and GST levels with no significant effect on SOD. Reversed effects of DMH/DSS were observed on DNA fragmentation, ACF multiplicity, and hyperplastic lesions in the nanoparticle-treated groups. Dysplasia, pleomorphic inflammatory cells, and hyperchromatic nuclei, the hallmarks of colon histology lesions in the DMH/DSS group, were significantly prevented by V. sieberiana-ZnONPs. Conclusions: This study demonstrated the preventive potential of V. sieberiana-ZnONPs against inflammation, apoptosis and DNA damage in chemically induced pre-colorectal cancer.