title: Therapeutic effect of hydrogen sulfide-releasing L-Dopa derivative ACS84 on 6-OHDA-induced Parkinson's disease rat model.
abstract: Parkinson's disease (PD), characterized by loss of dopaminergic neurons in the substantia nigra, is a neurodegenerative disorder of central nervous system. The present study was designed to investigate the therapeutic effect of ACS84, a hydrogen sulfide-releasing-L-Dopa derivative compound, in a 6-hydroxydopamine (6-OHDA)-induced PD model. ACS84 protected the SH-SY5Y cells against 6-OHDA-induced cell injury and oxidative stress. The protective effect resulted from stimulation of Nrf-2 nuclear translocation and promotion of anti-oxidant enzymes expression. In the 6-OHDA-induced PD rat model, intragastric administration of ACS84 relieved the movement dysfunction of the model animals. Immunofluorescence staining and High-performance liquid chromatography analysis showed that ACS84 alleviated the loss of tyrosine-hydroxylase positive neurons in the substantia nigra and the declined dopamine concentration in the injured striatums of the 6-OHDA-induced PD model. Moreover, ACS84 reversed the elevated malondialdehyde level and the decreased glutathione level in vivo. In conclusion, ACS84 may prevent neurodegeneration via the anti-oxidative mechanism and has potential therapeutic values for Parkinson's disease.
authors.affiliation: Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
authors.forename: Li
authors.initials: L
authors.lastname: Xie
authors.forename: Li-Fang
authors.initials: LF
authors.lastname: Hu
authors.forename: Xing Qi
authors.initials: XQ
authors.lastname: Teo
authors.forename: Chi Xin
authors.initials: CX
authors.lastname: Tiong
authors.forename: Valerio
authors.initials: V
authors.lastname: Tazzari
authors.forename: Anna
authors.initials: A
authors.lastname: Sparatore
authors.forename: Piero
authors.initials: P
authors.lastname: Del Soldato
authors.forename: Gavin Stewart
authors.initials: GS
authors.lastname: Dawe
authors.forename: Jin-Song
authors.initials: JS
authors.lastname: Bian
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use*; D000978:Antiparkinson Agents / Q000494:pharmacology / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004220:Disulfides / Q000494:pharmacology / Q000627:therapeutic use*; D004298:Dopamine / Q000378:metabolism; D059290:Dopaminergic Neurons / Q000187:drug effects / Q000502:physiology; D004790:Enzyme Induction / Q000187:drug effects; D015870:Gene Expression / Q000187:drug effects; D005721:Glutamate-Cysteine Ligase / Q000235:genetics / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007980:Levodopa / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D015227:Lipid Peroxidation; D008297:Male; D018384:Oxidative Stress; D016627:Oxidopamine; D010302:Parkinson Disease, Secondary / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D020218:Response Elements; D013378:Substantia Nigra / Q000187:drug effects / Q000473:pathology
chemical_list: C583845:ACS 84; D000975:Antioxidants; D000978:Antiparkinson Agents; D004220:Disulfides; D007980:Levodopa; D016627:Oxidopamine; D051547:Heme Oxygenase-1; D005721:Glutamate-Cysteine Ligase; C544143:GCLC protein, rat; D004298:Dopamine