Protective effect of Galantamine on attenuating Cisplatin-induced Neurotoxicity: An In-vitro and In-vivo approach

Abstract

Galantamine is a drug of choice for the treatment of Alzheimer's disease and possesses antioxidant, anti-inflammatory and cholinomimetic as non-FDA-approved indications. This study designed to explore the impact of Galantamine to attenuate cisplatin-induced neurotoxicity and oxidative stress. Experimental animals were segregated into five groups viz-a-viz group I as normal control, II as cisplatin control, and III-V as galantamine at varying doses, low (2.5mg/kg), medium (5mg/kg) and higher (10mg/kg). All the samples were orally administered, daily for 14 days. Cisplatin was injected intraperitoneally on day 8 to all groups except normal control. Assessment of neurotoxicity was done by measurement of a balance of antioxidant (GSH, SOD) and pro-oxidant (MDA), histopathological investigations. Dose-dependent significant (p<0.05) reduction in neurotoxicityhas been found by galantamine with reduction (p<0.01) in oxidant stress markers. Pronouncedreduction in apoptosis and elevation of disturbed hematological, and biochemical alterations were also observed with significance of p<0.001 in galantamine groups. We have observed that galantaminedose-dependentlyattenuates neurotoxicity, and oxidative stress, reversed the histopathological alterations and inhibits activated pro-inflammatory mediators (TNF-α). The research work provides drug repurposing of galantamine and providespreliminary ground for the treatment and management of cisplatin-induced neurotoxicity towards the clinical domain.