Curcumin alleviates arsenic trioxide-induced neural damage in the murine striatal region

Psychopharmacology (Berl). 2024 Oct 23. doi: 10.1007/s00213-024-06700-y. Online ahead of print.

Abstract

Rationale: Arsenic-induced neurotoxicity, with dose-dependent effects, is well-documented in rodents. Curcumin (CUR), a cost-effective plant polyphenol, shows neuroprotective effects by modulating oxidative stress, apoptosis, and neurochemistry. This study evaluates curcumin's neuroprotective potential against arsenic trioxide (As2O3) in the mouse striatal region.

Methods: Healthy adult male mice were chronically administered with varying concentrations of As2O3 (2, 4 and 8 mg/kg bw) alone and along with CUR (100 mg/kg bw) orally for 45 days. Towards the end of the experimental period, the animals were subjected to behavioural paradigms including open field task, novel object recognition, rota-rod, and Morris water maze. Striatal tissues were freshly collected from the animals on day 46 for biochemical analyses (MDA, GPx, and GSH). Additionally, perfusion-fixed brains were processed for morphological observations.

Results: Behavioural study showed an apparent decrease in certain cognitive functions (learning and memory) and locomotor activity in mice exposed to As2O3 compared to controls. Simultaneous treatment of As2O3 (2, 4 and 8 mg/kg bw) and curcumin (100 mg/kg bw) alleviated the As-induced locomotor and cognitive deficits. As2O3 alone exposure also exhibited a significant increase in oxidative stress marker (MDA) and a decrease in antioxidant enzyme levels (GPx, GSH). Morphological alterations were noted in mice subjected to elevated doses of As2O3 (4 and 8 mg/kg bw). However, these changes were reversed in mice who received As2O3 + CUR co-treatment.

Conclusions: Collectively, our findings indicate that curcumin offers neuroprotection to the striatal region against As2O3-induced behavioral deficits, as well as biochemical and morphological alterations.

Keywords: Arsenic; Basal Ganglia; Curcumin; Motor deficits; Oxidative stress.