Esculentin-2CHa (GA30) mitigates copper-induced redox imbalance and behavioural deficit in Drosophila melanogaster

Abstract Excess copper ion (Cu²⁺) has been implicated in various pathological conditions involving oxidative stress and inflammation. This study investigated neuroprotective effects of esculentin-2CHa-(GA30) on copper-induced toxicity in Drosophila melanogaster. Flies were treated with esculentin-2CHa (5.0 and 7.5 µM/kg diet) and/or Cu²⁺ (1mM) orally for 5 days. Effects of esculetin-2CHa-(GA30) on markers of redox-antioxidant status and neuro-behavioural activities were assessed. Esculetin-2CHa-(GA30) did not affect survival rate but reversed the effect of copper on eclosion rate. Esculetin-2CHa-(GA30) dose-dependently mitigated Cu²⁺-induced elevation of hydrogen peroxide (15.1–15.8%, P < 0.05), thiobarbituric reactive substance (37.2–55.1%, P < 0.01–0.001) and protein carbonyl (20.7–63.8%, P < 0.05–0.001). Esculetin-2CHa-(GA30) ameliorated Cu²⁺-induced inhibition of catalase (1.5–1.7-fold, P < 0.01–0.001), glutathione S-transferase activities (1.5–2.1-fold, P < 0.01–0.001) and decline in non-protein thiols levels (13.6–27.7%, P < 0.05). Esculetin-2CHa-(GA30) reduced Cu²⁺⁻induced elevation of monoamine oxidase (21.7–39.7%, P < 0.05–0.01) and acetylcholinesterase (40.1–55.9%, P < 0.01–0.001) activities. Copper-induced impaired locomotor activities were dose-dependently improved in esculentin-2CH-(GA30)-treated flies (21.4%, P < 0.05 and 72.1%, P < 0.01). Histological assessments indicated the ability of esculentin-2CHa-(GA30) to sequester Cu²⁺ in the microglia. In conclusion, esculentin-2CHa-(GA30) exhibited its neuroprotective effects through improved balance of redox status and associated behavioural characteristics. Further studies to delineate molecular mechanisms underlying observed effects would be required.