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

Abstract

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 Ginkgo 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 administered Ginkgo (50 mg/kg orally) daily for thirty days; and (4) Ginkgo+Cis group, rats received Ginkgo (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 Ginkgo and Cis reversed the adverse effect of Cis on the brain tissue. Moreover, co-administration of Ginkgo and Cis ameliorated Cis induced brain damage by reducing Amyloid precursor protein (APP), amyloid β (Aβ), P2Y12R and P2X7R mRNA expressions and proteins. Furthermore, Ginkgo regulated XIAP/BDNF expressions with a consequent decrease of caspase-3 and DNA fragmentation%. The current results concluded that concurrent treatment with Ginkgo 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.

Antioxidant and Anti-inflammatory Properties Mediate the Neuroprotective Effects of Hydro-ethanolic Extract of Tiliacora triandra Against Cisplatin-induced Neurotoxicity

“…39,40 Cisplatin generates reactive oxygen species (ROS), including hydrogen peroxide and hydroxyl radicals which attack lipid membrane and inhibit antioxidant enzyme activity to promote lipid peroxidation and oxidative stress, respectively. 29,41 In this study, the injected CDDP instigated preponderant elevations in the brain MDA levels in the CDDP model compared to the normal control. In addition, the brain activities of SOD, CAT, GSH, and GPx were also appreciably reduced compared to the normal control.…”

“…Accumulating evidence depicts neurotoxicity and/or CICI as the overriding off-target tissue toxicity of CDDP. 29 , 30 Cisplatin is a potent penetrator of the blood–brain barrier, and so it can debilitate mature neurons to induce cognitive impairment and behavioral deficit. 29 , 31 Cisplatin is clinically known to cause structural CNS mutilations which correlate with the cognitive deficits observed in CDDP‐treated patient.…”

“… 29 , 30 Cisplatin is a potent penetrator of the blood–brain barrier, and so it can debilitate mature neurons to induce cognitive impairment and behavioral deficit. 29 , 31 Cisplatin is clinically known to cause structural CNS mutilations which correlate with the cognitive deficits observed in CDDP‐treated patient. 23 Therefore, our study examined CICI and behavior of rats after CDDP injection via MWM and Y maze tests.…”

“…43,47 Several studies have shown that injection of CDDP induces increased expression of NF-κB, TNF-α, IL-6 and IL-1β and other inflammatory mediators. 24,29,43,47 The co-treatment with TT prevented overexpression of TNF-α, IL-6 and IL-1β compared to the CDDP rats. Tiliacora triandra leaves and a Thai polyherbal remedy containing TT have been shown to possess anti-inflammatory effects.…”

“…These results suggest that CDDP evokes apoptosis in the brain of experimental rats confirming data in published papers. 25,29 Interestingly, TT alleviated these altered pathological expression.…”