Zeolite Imidazole Framework-8 Exacerbates Astrocyte Activation and Oxidative Stress in the Brain of Rats

Metal-organic frameworks (MOFs) have been gaining significant attention due to their potential application in medicine. Here, we investigated the effect of zeolite imidazole framework-8 (ZIF-8) on neuro-behavioral parameters, histopathology, inflammation, and oxidative stress levels of rats' brain samples. Forty-eight male Wistar rats were injected by four injections of saline or ZIF-8 at different doses of 5, 10, or 20 mg/kg via the caudal vein. Y-Maze, Morris-Water Maze (MWM), and three chamber tests were conducted to explore working memory, spatial learning and memory, and social interactions, respectively. Histological staining and immunohistochemistry were used to evaluate pathological changes and astrocyte activation levels. The inflammation levels were measured using quantitative real-time reverse-transcription polymerase chain reaction (qRT-PCR). The total antioxidant capacity (TAC) and oxidative stress production were assessed by biochemical assays. The results showed that ZIF-8 induces neuromotor impairment dose-dependently. Although histopathological studies indicated increased neuronal loss, inflammatory changes, and elevated active astrocytes in the hippocampus, the expression levels of IL-1β and TNF-α were not significantly increased in ZIF-8-treated rats. The TAC level significantly reduced and the malondialdehyde (MDA) level remarkably increased in the brain tissues. Our findings suggest that administration of ZIF-8 induce neuromotor impairment, probably through amplified inflammation and oxidative stress.