Evaluation of the Mitigatory Potential of Nigella sativa Oil on Cisplatin-Induced Toxicity in the Prefrontal Cortex of Adult Wistar Rats

Cisplatin remains a mainstay of modern cancer chemotherapy, but its clinical utility is constrained by dose-limiting toxicities, including neurotoxicity affecting the prefrontal cortex (PFC), a brain region central to executive function, working memory, and emotional regulation. This toxicity is driven by oxidative stress, neuroinflammation, and mitochondrial dysfunction, for which effective, well-tolerated adjunctive agents remain scarce. This study evaluated the mitigatory potential of Nigella sativa oil (NSO) against cisplatin-induced toxicity in the PFC of adult Wistar rats. Thirty adult male Wistar rats were randomly allocated into five groups of six: control, cisplatin-only (10 mg/kg, single intraperitoneal dose), NSO pretreatment plus cisplatin, cisplatin plus NSO post-treatment, and NSO-only (2 ml/kg orally, daily for 28 days). Body and brain weights were recorded, and prefrontal cortical tissue was analysed for oxidative stress markers (superoxide dismutase, catalase, lipid peroxidation), the pro-inflammatory cytokine tumour necrosis factor-alpha (TNF-α), and the mitochondrial enzymes lactate dehydrogenase and succinate dehydrogenase, alongside Haematoxylin and Eosin and Cresyl violet staining. Cisplatin produced a progressive decline in body weight, elevated lipid peroxidation, TNF-α and lactate dehydrogenase, reduced succinate dehydrogenase activity, and marked pyknosis, vacuolation and loss of Nissl substance in prefrontal cortical neurons. NSO administration, whether before or after cisplatin exposure, significantly attenuated these derangements, most consistently for the inflammatory, mitochondrial and histomorphological parameters, with a more modest effect on lipid peroxidation and no significant change in superoxide dismutase or catalase activity. These findings indicate that Nigella sativa oil possesses genuine, timing-independent neuroprotective potential against cisplatin-induced prefrontal cortical toxicity, supporting further molecular, behavioural and clinical evaluation of its candidacy as an adjunctive agent in platinum-based chemotherapy regimens.