Abstract
It is well established that inhalation exposure to xylene causes significant learning impairments and neurobehavioral toxicity by altering lipid environments in nerve membranes and affecting neurotransmitter levels. Royal jelly (RJ) has been shown to exhibit potent antioxidant properties that can protect the hippocampus from oxidative damage. The present research was designed to investigate the neuroprotective potential of RJ in mitigating hippocampal injury induced by short-term and long-term xylene inhalation exposure. In this experiment, 48 male Wistar rats were randomly assigned to short-term and long-term groups, each consisting of control, RJ, xylene, and xylene + RJ treatments. Rats were exposed to xylene via inhalation for 6 h daily at a concentration of 500 ppm, while RJ was administered orally at a dose of 200 mg/kg. After 8 weeks, spatial memory and anxiety level were evaluated. Apoptosis and cell necrosis in the hippocampus were identified using the TUNEL method and hematoxylin-eosin staining. Additionally, oxidative stress biomarkers and the expression of apoptosis-related genes in hippocampal tissue were investigated. The results revealed that xylene exposure caused a significant impairment in spatial working memory performance, as reflected by reductions in arm entries and alternation percentage, along with a significant suppression of antioxidant enzyme activities (CAT, TAC, SOD, and GPx) compared to the control group. Additionally, xylene exposure significantly heightened anxiety-like behaviors, elevated MDA levels, increased the number of TUNEL-positive apoptotic cells in the hippocampus, and upregulated the expression of apoptotic markers including caspase-3, Bax, and p53 genes, alongside promoting necrotic cell death. Co-treatment with RJ significantly improved behavioral alterations, enhanced antioxidant activity, and decreased hippocampal apoptosis/necrosis. In conclusion, RJ mitigates xylene-induced neurotoxicity via antioxidant and anti-apoptotic pathways, suggesting therapeutic potential against xylene-related cognitive and neuronal damage.