Low Molecular Weight Sulfated Chitosan: Neuroprotective Effect on Rotenone-Induced In Vitro Parkinson’s Disease

• Published in: Neurotoxicity research 2019-04, Vol.35 (3), p.505-515
• Main Authors: Manigandan, Venkatesan, Nataraj, Jagatheesan, Karthik, Ramachandran, Manivasagam, Thamilarasan, Saravanan, Ramachandran, Thenmozhi, Arokyasamy Justin, Essa, Musthafa Mohamed, Guillemin, Gilles J.
• Format: Article
• Language: English
• Subjects: Antiparkinson Agents - pharmacology; Apoptosis - drug effects; Apoptosis - physiology; Biomedical and Life Sciences; Biomedicine; Cell Biology; Cell Line, Tumor; Cell Survival - drug effects; Cell Survival - physiology; Chitosan - analogs & derivatives; Chitosan - pharmacology; DNA Fragmentation - drug effects; Dose-Response Relationship, Drug; Humans; Membrane Potential, Mitochondrial - drug effects; Membrane Potential, Mitochondrial - physiology; Neurobiology; Neurochemistry; Neurology; Neurons - drug effects; Neurons - metabolism; Neurons - pathology; Neuroprotective Agents - pharmacology; Neurosciences; Original Article; Oxidative Stress - drug effects; Oxidative Stress - physiology; Parkinsonian Disorders - drug therapy; Parkinsonian Disorders - metabolism; Parkinsonian Disorders - pathology; Pharmacology/Toxicology; Reactive Oxygen Species - metabolism; Rotenone
• ISSN: 1029-8428; 1476-3524
• DOI: 10.1007/s12640-018-9978-z

The present investigation was an attempt to study the effect of low molecular weight sulfated chitosan (LMWSC) on in vitro rotenone model of Parkinson’s disease (PD) by evaluating cell viability, oxidative stress, mitochondrial membrane potential, DNA fragmentation, and apoptosis. Incubation of SH-SY5Y cells with 100 nm rotenone resulted in neuronal cell death, redox imbalanced mitochondrial dysfunction, DNA fragmentation, condensation, and apoptotic cellular morphology. Rotenone exposure enhanced the expression of preapoptotic (cytochrome C (cyto c), caspase-3, -8, -9, and Bax) and down-regulated the expression of anti-apoptotic (Bcl-2) markers. Reduction of the intracellular reactive oxygen species (ROS) levels ensued due to pretreatment of LMWSC along with consequent normalization of antioxidant enzymes, mitigation of rotenone induced mitochondrial dysfunction and apoptosis. Our current findings suggested that LMWSC exhibit the pronounced neuroprotective effects, which could be due to its antioxidant, mitochondrial protection, and anti-apoptotic properties. We thus conclude that LMWSC could be developed as a novel therapeutic molecule for the benefit of reducing the consequences of PD. However, further extensive preclinical and clinical studies are warranted.