Ginkgo bilobaAlleviates Cisplatin-Mediated Neurotoxicity in Rats via Modulating APP/A beta/P2X7R/P2Y12R and XIAP/BDNF-Dependent Caspase-3 Apoptotic Pathway

Neurotoxicity is an obvious adverse effect in Patients encountering a complete course of chemotherapy. The present work is conducted to evaluate the neuroprotective effect ofGinkgo biloba(Ginkgo) 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 administeredGinkgo(50 mg/kg orally) daily for thirty days; and (4) Ginkgo+Cis group, rats receivedGinkgo(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 ofGinkgoand Cis reversed the adverse effect of Cis on the brain tissue. Moreover, co-administration ofGinkgoand Cis ameliorated Cis induced brain damage by reducing Amyloid precursor protein (APP), amyloid beta (A beta), P2Y12R and P2X7R mRNA expressions and proteins. Furthermore,Ginkgoregulated XIAP/BDNF expressions with a consequent decrease of caspase-3 and DNA fragmentation%. The current results concluded that concurrent treatment withGinkgocan 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/A beta/P2Y12R/P2X7R and XIAP/BDNF signaling pathways.