Curcumin Nanoparticles Attenuate Neurochemical and Neurobehavioral Deficits in Experimental Model of Huntington’s Disease

• Published in: Neuromolecular medicine 2014-03, Vol.16 (1), p.106-118
• Main Authors: Sandhir, Rajat, Yadav, Aarti, Mehrotra, Arpit, Sunkaria, Aditya, Singh, Amandeep, Sharma, Sadhna
• Format: Article
• Language: English
• Subjects: 3-Nitropropionic acid; Animals; Ataxia - drug therapy; Ataxia - etiology; Biomedical and Life Sciences; Biomedicine; Corpus Striatum - pathology; Curcumin - administration & dosage; Curcumin - therapeutic use; Disease Models, Animal; Drug Evaluation, Preclinical; Female; Glutathione - metabolism; Humans; Huntington Disease - chemically induced; Huntington Disease - drug therapy; Huntington Disease - metabolism; Huntington Disease - psychology; Internal Medicine; Lameness, Animal - chemically induced; Lameness, Animal - drug therapy; Lipid Peroxidation - drug effects; Mitochondria - drug effects; Mitochondria - metabolism; Motor Activity - drug effects; Nanoparticles; Neurology; Neurosciences; NF-E2-Related Factor 2 - biosynthesis; NF-E2-Related Factor 2 - genetics; Nitro Compounds - toxicity; Original Paper; Oxidative Stress; Phytotherapy; Propionates - toxicity; Random Allocation; Rats; Rats, Wistar; Reactive Oxygen Species - metabolism; Superoxide Dismutase - metabolism
• ISSN: 1535-1084; 1559-1174
• DOI: 10.1007/s12017-013-8261-y

Till date, an exact causative pathway responsible for neurodegeneration in Huntington’s disease (HD) remains elusive; however, mitochondrial dysfunction appears to play an important role in HD pathogenesis. Therefore, strategies to attenuate mitochondrial impairments could provide a potential therapeutic intervention. In the present study, we used curcumin encapsulated solid lipid nanoparticles (C-SLNs) to ameliorate 3-nitropropionic acid (3-NP)-induced HD in rats. Results of MTT (3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide) assay and succinate dehydrogenase (SDH) staining of striatum revealed a marked decrease in Complex II activity. However, C-SLN-treated animals showed significant increase in the activity of mitochondrial complexes and cytochrome levels. C-SLNs also restored the glutathione levels and superoxide dismutase activity. Moreover, significant reduction in mitochondrial swelling, lipid peroxidation, protein carbonyls and reactive oxygen species was observed in rats treated with C-SLNs. Quantitative PCR and Western blot results revealed the activation of nuclear factor-erythroid 2 antioxidant pathway after C-SLNs administration in 3-NP-treated animals. In addition, C-SLN-treated rats showed significant improvement in neuromotor coordination when compared with 3-NP-treated rats. Thus, the results of this study suggest that C-SLNs administration might be a promising therapeutic intervention to ameliorate mitochondrial dysfunctions in HD.