Abstract

 Cyclophosphamide (CYP), a widely used chemotherapeutic agent, is known to induce neurotoxicity primarily through oxidative stress, inflammation, and apoptosis. This research aimed to evaluate the neuroprotective potential of ellagic acid (EA), against CYP-induced cerebellar injury in rats. Thirty-two male rats were grouped into: Control, EA, CYP, and EA + CYP. EA was administered intraperitoneally at 10 mg/kg for five consecutive days, while CYP take a single intraperitoneal dose of 200 mg/kg on day five. Biochemical, histopathological, and immunological assessments were conducted on cerebellar tissues. CYP administration significantly elevated malondialdehyde (MDA) levels and reduced antioxidant enzyme activities (SOD and CAT), indicating oxidative stress. It also upregulated the TLR4/MyD88/NF-κB pathway and increased (TNF-α, IL-6, IL-1β), along with apoptotic markers (caspase-3, Bax) and reduced anti-apoptotic Bcl-2 expression. In contrast, EA pretreatment markedly attenuated these effects by restoring antioxidant defenses, suppressing inflammatory signaling, and reducing apoptotic activity. Histological analysis further confirmed the protective role of EA in preserving cerebellar architecture and Purkinje cell integrity. These findings suggest that EA offers significant protection against CYP-induced cerebellar damage, supporting its potential as a neuroprotective agent in chemotherapy-associated neurotoxicity.

Keywords: Cyclophosphamide, ellagic acid, cerebellum, oxidative stress, inflammation, apoptosis