<i>Ginkgo biloba</i> Alleviates Cisplatin-Mediated Neurotoxicity in Rats via Modulating APP/Aβ/P2X7R/P2Y12R and XIAP/BDNF-Dependent Caspase-3 Apoptotic Pathway

• Main Authors: Dina H. Gomaa, Walaa G. Hozayen, Haidy Al-shafeey, Asmaa Mohammed M. Hussein Elkelawy, Khalid S. Hashem
• Format: Article
• Language: English
• Published: MDPI AG 2020-07-01
• Series: Applied Sciences
• Subjects: cisplatin; neuro toxicity; <i>Ginkgo biloba</i>; XIAP; APP; BDNF
• Online Access: https://www.mdpi.com/2076-3417/10/14/4786

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.