Protective effects of curcumin/magnesium oxide nanoparticles on ketamine-induced neurotoxicity in the mouse hippocampus.

Background and purpose: Nanotechnology can improve drug delivery by enhancing cell selectivity, releasing at specific target sites, and improving bioavailability while reducing adverse events and potential treatment costs. The current study aimed to synthesize curcumin/magnesium oxide (Cur/MgO) nanoparticles (NPs) and evaluate their neuroprotective effects in a mouse model of ketamine-induced neurotoxicity.

Experimental approach: XRD, FE-SEM, and a particle size analyzer determined the average crystalline and particle sizes. UV-Vis examined absorption patterns, and FT-IR spectroscopy analyzed the functional groups involved in the reaction. To evaluate the effectiveness of Cur/MgO NPs on ketamine-induced neurotoxicity, male BALB/c mice were divided into 7 groups and received the following treatments (intraperitoneally, daily for 2 weeks). Groups 1 and 2 received normal saline (0.2 mL) and ketamine (25 mg/kg). Group 3 received curcumin (40 mg/kg) and ketamine (25 mg/kg). Groups 4-6 received ketamine (25 mg/kg) and Cur/MgO NPs (10, 20, and 40 mg/kg). Group 7 received MgO (5 mg/kg) and ketamine (25 mg/kg). Finally, the hippocampal tissues were examined morphologically and analyzed for oxidative stress, inflammation, apoptotic markers, and mitochondrial quadruple complex enzymes.

Results/findings: Both Cur/MgO NPs and curcumin reduced IL-1β, TNF-α, Bax, and MDA levels and GSSG content and increased GSH, Bcl-2, GPx, GR, and SOD. Cur/MgO NPs and curcumin also increased mitochondrial quadruple complex enzymes and inhibited histological changes in the dentate gyrus and CA1 hippocampus areas in ketamine-induced neurotoxicity.

Conclusion and implications: Cur/MgO NPs were more neuroprotective against the ketamine-induced histomorphological changes, inflammation, apoptosis, and oxidative stress than curcumin alone.