Protective effect of nanocurcumin against neurotoxicity induced by doxorubicin in rat's brain.

ABSTRACT

Cognitive impairment is one of the serious side effects that cancer-treated patients suffer from after treatment by doxorubicin (DOX). Investigating the mechanisms underlying this impairment is crucial for its treatment or prevention. The current study investigates the cortical and hippocampal neurochemical changes induced by an acute dose of DOX (20 mg/kg, i.p.) and evaluates the neuroprotective effect of nanocurcumin (NC) (50 mg/kg, p.o.) against these changes. Animals were randomly divided into four groups, control, rats treated with either NC or DOX, and the fourth group treated with NC prior to DOX. Cortical dopamine level has significantly increased (71.88 %) after DOX injection. This was associated with a significant rise in the levels of lipid peroxidation (183.99 %, 201.4 %) and nitric oxide (36.54 %, 55 %) and a significant reduction in reduced glutathione (13 %, 21.44 %) in the cortex and hippocampus, respectively. In addition, DOX inhibited the cortical and hippocampal activities of acetylcholinesterase (94.82 %, 62.75 %) and monoamine oxidase (64.40 %, 68.84 %), respectively. Protection with NC mitigates the changes induced in the oxidative stress parameters by DOX. However, the effect on the activities of AchE and MAO was insignificant. This was reflected in the level of dopamine that showed non-significant changes in comparison to control and DOX-treated rats. The present findings indicate that oxidative stress, inhibition in AchE, MAO, and the subsequent elevation in dopamine could have a crucial role in mediating the chemo-brain adverse effects induced by DOX. In addition, protection with NC mitigated some of these adverse effects thus rendering DOX more tolerable.