Ameliorative Effect of Green Bimetallic Zinc Oxide-Magnesium Oxide Nanoparticles Against Gastric Ulcer in Rats via Modulation of Oxidative Stress, Inflammatory Cascades, Nrf2/NF-κB Signaling, Angiogenic VEGF Expression

Gastric ulcers are a highly prevalent gastrointestinal disorder, impacting a significant portion of the global population, and have serious complications, such as bleeding, perforation, and malignant transformation. The ethanol-induced gastric ulcer model provides a distinct advantage because it faithfully mimics clinical features seen in acute peptic ulcer disease. This study aimed to evaluate the effect of bimetallic zinc oxide-magnesium oxide nanoparticles (ZnO-MgO NPs) on ethanol-induced gastric ulcer in albino rats. Different monometallic and bimetallic NPs have been completely characterized and synthesized by an eco-friendly and cost-effective method utilizing Gum Arabic as a strong reducing agent. Fifty rats were divided into five groups: control, ethanol-induced gastric ulcer, ulcerated rats treated daily for 14 days with ZnO NPs, MgO NPs, or bimetallic ZnO-MgO NPs. Rat's stomachs underwent biochemical estimation for catalase (CAT), superoxide dismutase (SOD), Malondialdehyde (MDA), Nuclear factor erythroid 2-related factor 2 (Nrf2), Nuclear factor kappa b (NF-κB), and Tumor necrosis factor alpha (TNF-α), as well as, histological, immunohistochemical (including Vascular endothelial growth factor, VEGF, and Inducible nitric oxide synthase, iNOS), and Scanning electron microscopic examinations. The synthesized monometallic and bimetallic NPs had a semi-spherical shape, with an average diameter of 40.44 ± 1.3 nm (for ZnO NPs), 35.56 ± 1.2 nm (for MgO NPs) and 48.46 ± 1.5 nm (for ZnO-MgO NPs). In alcohol-induced gastric ulcer group, ulceration with a significant increase in histopathological changes was noticed in the form of ulceration, inflammatory infiltrations, activated mast cells, edema, and hemorrhage. Decrease activities of CAT, SOD, and Nrf2, as well as an increase in MDA, TNF-α, and NF-κB, with upregulation of iNOS, and downregulation of VEGF, which were improved partially by treatment of either ZnO NPs or MgO NPs. ZnO-MgO NPs restored the normal histological picture of the rat's stomach. Bimetallic ZnO-MgO NPs have a more powerful curative effect than each one of ZnO NPs or MgO NPs; separately, which can be explained by the synergetic effect of them leading to more potent antioxidant and anti-inflammatory effects.