Curcumin Administration Mitigates Cyclophosphamide-Induced Oxidative Damage and Restores Alteration of Enzymes...

The use of chemotherapeutic drugs is associated with oxidative damage, cognitive dysfunction, and brain damage. This study sought to investigate the neuroprotective effect of curcumin against cognitive problems associated with treatment with cyclophosphamide via assessment of biomolecules associated with cognitive function in rats' brain homogenates. Rats were divided in to five groups: Control (vehicle), CUR (curcumin [20 mg/kg]), CPA (cyclophosphamide [150 mg/kg]), CUR1 + CPA (curcumin [20 mg/kg] and cyclophosphamide [150 mg/kg]), and CPA + CUR2 (cyclophosphamide [150 mg/kg] and curcumin [20 mg/kg]). After the treatment, cognitive behavior was assessed and enzymes [cholinesterases, purinergic enzymes, arginase, and angiotensin I-converting enzyme] associated with cognitive function were examined. Oxidative stress parameters [total thiol, non-protein thiol, malondialdehyde, and nitric oxide] including the expression of caspase-3 were also assessed in rats' brain. Our results showed that curcumin improved cognitive behavior, attenuated cholinergic deficit as revealed by the inhibition of cholinesterases, and improved purinergic signaling in cyclophosphamide-treated rats. Furthermore, curcumin reduced angiotensin-I-converting enzyme and arginase activities before and after treatment with cyclophosphamide. Curcumin also improved redox balance and showed protection against cyclophosphamide-induced oxidative damage to rats' brain via an increase in protein and non-protein thiols and nitric oxide levels as well as a significant reduction in malondialdehyde levels. Curcumin also prevented neuronal degeneration in different brain regions and reduced caspase-3 expression. Hence this study suggests that pre and post-treatment with curcumin improved neurobehavior, modulates some biomarkers associated with cognitive function and exhibit neuroprotection against cyclophosphamide-induced neurotoxicity in rats.