Evaluating the Protective Effects and Mechanisms of Diallyl Disulfide on Interlukin-1β-Induced Oxidative Stress and Mitochondrial Apoptotic Signaling Pathways in Cultured Chondrocytes.
The protective effects and mechanisms of DADS on IL-1β-mediated oxidative stress and mitochondrial apoptosis were investigated in C28I2 human chondrocytes. The effect of various concentrations of DADS (1, 5 10, 25, 50, and 100 μM) on C28I2 cell viability was evaluated in different times (2, 4, 8, 16, and 24 h) to obtain the non-cytotoxic concentrations of drug by MTT-assay. The protective effect of non-toxic concentrations of DADS on experimentally induced oxidative stress and apoptosis by IL-1β in C28I2 was evaluated. The effects of DADS on IL-1β-induced intracellular ROS production and lipid peroxidation were detected and the proteins expression of Nrf2, Bax, Bcl-2, caspase-3, total and phosphorylated JNK, and P38 MAPKs were analyzed by Western blotting. The mRNA expression of detoxifying phase II/antioxidant enzymes including heme oxygenase-1, NAD(P)H quinine oxidoreductase, glutathione S-transferase-P1, catalase, superoxide dismutase-1, glutathione peroxidase-1, -3, -4 were evaluated by reverse transcription-polymerase chain reaction. DADS in 1, 5, 10, and 25 μM concentrations had no cytotoxic effect after 24 h. Pretreatment with DADS remarkably increased Nrf2 nuclear translocation as well as the genes expression of detoxifying phase II/antioxidant enzymes and reduced IL-1β-induced elevation of ROS, lipid peroxidation, Bax/Bcl-2 ratio, caspase-3 activation, and JNK and P38 phosphorylation. DADS could considerably reduce IL-1β-induced oxidative stress and consequent mitochondrial apoptosis, as the major mechanisms of chondrocyte cell death in an experimental model of osteoarthritis. It may be considered as natural product in protecting OA-induced cartilage damage in clinical setting. J. Cell. Biochem. 118: 1879-1888, 2017. © 2017 Wiley Periodicals, Inc.
RAZI Drug Research Center, Iran University of Medical Sciences, Tehran, Iran.|Department of Pharmacology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.
Azam
A
Hosseinzadeh
Department of Orthopedics Surgery, Bone and Cartilage Reconstruction Joint Research Center, Shafa Orthopedic Hospital, Iran University of Medical Sciences, Tehran, Iran.
Davood
D
Jafari
Tissue Engineering Group (NOCERAL), Faculty of Medicine, Department of Orthopedic Surgery, University of Malaya, Kuala Lumpur, Malaysia.
Tunku
T
Kamarul
Department of Orthopedics Surgery, Bone and Cartilage Reconstruction Joint Research Center, Shafa Orthopedic Hospital, Iran University of Medical Sciences, Tehran, Iran.
Abolfazll
A
Bagheri
RAZI Drug Research Center, Iran University of Medical Sciences, Tehran, Iran.|Department of Pharmacology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.|Tissue Engineering Group (NOCERAL), Faculty of Medicine, Department of Orthopedic Surgery, University of Malaya, Kuala Lumpur, Malaysia.
Ali M
AM
Sharifi
D000498:Allyl Compounds / Q000494:pharmacology*; D000975:Antioxidants / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D002374:Catalase / Q000378:metabolism; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D019902:Chondrocytes / Q000187:drug effects* / Q000378:metabolism*; D004220:Disulfides / Q000494:pharmacology*; D005979:Glutathione Peroxidase / Q000378:metabolism; D006801:Humans; D053583:Interleukin-1beta / Q000494:pharmacology*; D015227:Lipid Peroxidation / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D015398:Signal Transduction / Q000187:drug effects; D000072105:Superoxide Dismutase-1 / Q000378:metabolism; D000094765:Glutathione Peroxidase GPX1
D000498:Allyl Compounds; D000975:Antioxidants; D004220:Disulfides; D053583:Interleukin-1beta; D051267:NF-E2-Related Factor 2; C028009:diallyl disulfide; D002374:Catalase; D005979:Glutathione Peroxidase; D000072105:Superoxide Dismutase-1; D000094765:Glutathione Peroxidase GPX1; C000722067:GPX1 protein, human
APOPTOSIS; DIALLYL DISULFIDE; INTERLUKIN-1β; OSTEOARTHRITIS; REACTIVE OXYGEN SPECIES