TY - JOUR
T1 - Low Molecular Weight Sulfated Chitosan
T2 - Neuroprotective Effect on Rotenone-Induced In Vitro Parkinson’s Disease
AU - Manigandan, Venkatesan
AU - Nataraj, Jagatheesan
AU - Karthik, Ramachandran
AU - Manivasagam, Thamilarasan
AU - Saravanan, Ramachandran
AU - Thenmozhi, Arokyasamy Justin
AU - Essa, Musthafa Mohamed
AU - Guillemin, Gilles J.
N1 - Funding Information:
Funding Information The Senior Research Fellowship was funded and supported by the Council of Scientific & Industrial Research (CSIR), New Delhi, India.
Publisher Copyright:
© 2018, Springer Science+Business Media, LLC, part of Springer Nature.
PY - 2019/4/15
Y1 - 2019/4/15
N2 - 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.
AB - 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.
KW - Apoptosis
KW - Mitochondrial dysfunction
KW - Neuronal damage
KW - Oxidative stress
KW - Rotenone
KW - Sulfated chitosan
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U2 - 10.1007/s12640-018-9978-z
DO - 10.1007/s12640-018-9978-z
M3 - Article
C2 - 30426393
AN - SCOPUS:85056473058
SN - 1029-8428
VL - 35
SP - 505
EP - 515
JO - Neurotoxicity Research
JF - Neurotoxicity Research
IS - 3
ER -