title: A novel therapeutic application of solid lipid nanoparticles encapsulated thymoquinone (TQ-SLNs) on 3-nitroproponic acid induced Huntington's disease-like symptoms in wistar rats.
abstract: Huntington's disease (HD), a devastating neurodegenerative disease causing a remarkable pathogenesis involves mitochondrial dysfunction and bioenergetics failure. 3-Nitropropionic acid (3-NP) is a unique toxin model of HD that are mainly confined to mitochondrial complex-II inhibition and free radical generation. Recently, several nanoparticle formulations were developed to treat against various neurodegenerative diseases including HD. One among them is solid lipid nanoparticles (SLNs), a colloidal carrier designed to enhance the brain drug delivery and to prolong the bio-availability of drugs in the system. Hence, the present study was framed to evaluate solid lipid nanoparticles encapsulated thymoquinone (TQ-SLNs) in comparison with thymoquinone suspension (TQ-S) against 3-NP induced behavioral despair, oxidative injury and striatal pathology. This study reports that theTQ-SLNs (10 and 20 mg/kg) and TQ-S (80 mg/kg) treated animals showed a significant (P < 0.01) improvement in the muscle strength, rigidity, movement and memory performances on 7th and 14th day behavioral analysis than TQ-S (40 mg/kg) treated group. Similarly, TQ-SLNs highly attenuated the levels of oxidative stress markers such as LPO, NO and protein carbonylsin 3-NP induced animals. Further, TQ-SLNs significantly restored the antioxidant defense system, controls the mitochondrial SDH inhibition and alleviates anti-cholinergic effect upon 3-NP induction. In addition, TQ-SLNs efficiently protected the striatal structural microelements against 3-NP toxicity, which was confirmed by light microscopic studies. Thus, the present investigation, collectively suggests that the low dose of TQ-SLNs supplementation is highly sufficient to attain the effect of TQ-S (80 mg/kg) to attenuate behavioral, biochemical and histological modifications in 3-NP exposed HD model.
authors.affiliation: Department of Medical Biochemistry, Dr. ALM Post Graduate Institute of Basic Medical Sciences, University of Madras, Taramani Campus, Chennai, 600 113, Tamil Nadu, India.
authors.forename: Surekha
authors.initials: S
authors.lastname: Ramachandran
authors.affiliation: Department of Medical Biochemistry, Dr. ALM Post Graduate Institute of Basic Medical Sciences, University of Madras, Taramani Campus, Chennai, 600 113, Tamil Nadu, India. Electronic address: drsumathi.bioscience@gmail.com.
authors.forename: Sumathi
authors.initials: S
authors.lastname: Thangarajan
mesh_terms: D000818:Animals; D016227:Benzoquinones / Q000008:administration & dosage / Q000627:therapeutic use*; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D004337:Drug Carriers / Q000737:chemistry; D006816:Huntington Disease / Q000139:chemically induced* / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008055:Lipids / Q000737:chemistry; D008297:Male; D008568:Memory / Q000187:drug effects; D053758:Nanoparticles / Q000737:chemistry; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D009574:Nitro Compounds; D018384:Oxidative Stress / Q000187:drug effects; D011422:Propionates; D017208:Rats, Wistar; D065854:Spatial Navigation / Q000187:drug effects
chemical_list: D016227:Benzoquinones; D004337:Drug Carriers; D008055:Lipids; D018696:Neuroprotective Agents; D009574:Nitro Compounds; D011422:Propionates; C003466:thymoquinone; C015392:3-nitropropionic acid
keywords: 3-Nitropropionic acid; Histopathology; Huntington’s disease; Oxidative stress; Solid lipid nanoparticle; Thymoquinone