The protective effects of thymoquinone on the cerebellum and hippocampus of rats treated with diisobutyl phthalate.

Diisobutyl phthalate (DiBP) is a widely used industrial plasticizer, and growing experimental evidence suggests that it may exert adverse effects on the nervous system. Thymoquinone (TQ), the major bioactive constituent of Nigella sativa, has attracted considerable attention because of its reported neuroprotective effects in experimental models of neurotoxicity. The present study aimed to investigate the effects of prepubertal DiBP exposure on cerebellar and hippocampal tissues and to evaluate the potential protective effects of TQ in rats. Forty-nine male Wistar albino rats were divided into seven groups: Control, vehicle control, 500mg/kg DiBP, 750mg/kg DiBP, 10mg/kg TQ, 500mg/kg DiBP+10mg/kg TQ, and 750mg/kg DiBP+10mg/kg TQ. DiBP and TQ were administered orally once daily for 30 days. Histopathological, histomorphometric, and immunohistochemical evaluations were performed in cerebellar and hippocampal tissues. DiBP exposure induced significant histopathological and histomorphometric alterations characterized by neuronal degeneration, Purkinje cell loss, disrupted histoarchitectural organization, reduced neuronal counts in the CA1, CA2, CA3, and dentate gyrus regions, and increased glial fibrillary acidic protein (GFAP)-immunoreactive astrocyte numbers in both cerebellar and hippocampal tissues (P < 0.05). These alterations were more pronounced in the 750mg/kg DiBP group. In addition, DiBP exposure significantly increased 8-OHdG, TNF-α, and cleaved caspase-3 immunoreactivity in both brain regions (P < 0.05). In contrast, TQ administration attenuated the DiBP-induced histopathological, histomorphometric, and immunohistochemical alterations, which was accompanied by the partial preservation of neuronal morphology and tissue architecture, as well as reduced GFAP immunoreactivity (P < 0.05). TQ co-administration also significantly reduced the DiBP-associated increases in 8-OHdG, TNF-α, and cleaved caspase-3 immunoreactivity in both the cerebellum and hippocampus (P < 0.05). Overall, these findings suggest that TQ exerts protective effects against DiBP-induced neurotoxicity.