| Summary: | Neurotoxicity is an obvious adverse effect in Patients encountering a complete course of chemotherapy. The present work is conducted to evaluate the neuroprotective effect of <i>Ginkgo biloba</i> (<i>Ginkgo</i>) against the neurotoxicity induced by Cisplatin (Cis) in rats. Forty male Wistar albino rats were arranged into four groups: (1) Control group, rats were given saline; (2) Cis group, rats were injected by Cis 2 mg/kg body weight i.p., twice a week starting on the fifth day for thirty days; (3) Ginkgo group, rats were administered <i>Ginkgo</i> (50 mg/kg orally) daily for thirty days; and (4) Ginkgo+Cis group, rats received <i>Ginkgo</i> (50 mg/kg orally) daily and on the fifth day, rats were injected with Cis (2 mg/Kg body weight i.p.) twice a week for thirty days. Cis significantly increased Gamma glutamyltransferase (GGT) and Acetyl Cholinesterase (CHE) as compared to the control group and also disturbed cerebral oxidative/antioxidant redox. Co-administration of <i>Ginkgo</i> and Cis reversed the adverse effect of Cis on the brain tissue. Moreover, co-administration of <i>Ginkgo</i> and Cis ameliorated Cis induced brain damage by reducing Amyloid precursor protein (APP), amyloid β (Aβ), P2Y12R and P2X7R mRNA expressions and proteins. Furthermore, <i>Ginkgo</i> regulated XIAP/BDNF expressions with a consequent decrease of caspase-3 and DNA fragmentation%. The current results concluded that concurrent treatment with <i>Ginkgo</i> can mitigate neurotoxicity mediated by Cis in experimental animals through exhibiting antioxidant effect by restoring cerebral oxidative/antioxidant redox and anti-apoptotic effect via regulating cerebral APP/Aβ/P2Y12R/P2X7R and XIAP/BDNF signaling pathways.
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