Oxidative stress-mediated neurotoxicity of para-xylene and neuroprotection by gluconolactone in Xenopus laevis

Para-xylene (PX) is a commonly used industrial solvent that poses significant neurotoxic risks, however, the underlying physiological mechanisms remain inadequately defined. In this study, we exposed Xenopus laevis tadpoles to PX and used RNA sequencing and enzymatic assays to explore the underlying neurotoxic mechanisms. Our findings revealed a marked reduction in the expression of genes associated with oxidative stress defense, notably superoxide dismutase (sod1.L) and catalase (cat.L). These observations were validated by quantitative PCR and enzyme activity assays, which confirmed decreased SOD and CAT activities alongside elevated levels of oxidative damage markers, including malondialdehyde (MDA) and lactate dehydrogenase (LDH). PX treatment leads to increased neuronal apoptosis and abnormal swimming behavior. Notably, the co-administration of glucuronolactone (GA) with PX restored the activities of these critical enzymes and reduced oxidative damage, suggesting a mitigating effect of GA on PX-induced stress. Further validation using diethyldithiocarbamate (DDC) to inhibit SOD activity underscored the enzyme's pivotal role in mediating PX toxicity. Additionally, TUNEL assays demonstrated that GA effectively prevented neuronal apoptosis in the optic tectum, while behavioral assessments indicated a recovery in normal swimming patterns. Collectively, these results indicate that PX exposure triggers oxidative stress, leading to neuronal damage and behavioral deficits, whereas GA confers a protective effect by re-establishing antioxidant balance and reducing cell death.