Evaluating the Protective Effects and Mechanisms of Diallyl Disulfide on Interlukin‐1β‐Induced Oxidative Stress and Mitochondrial Apoptotic Signaling Pathways in Cultured Chondrocytes

Abstract

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.

Intraarticular Administration Effect of Hydrogen Sulfide on an In Vivo Rat Model of Osteoarthritis

“…Wu et al (2016) observed that S-propargyl-cysteine, an endogenous inductor of H 2 S synthesis, activates Nrf-2 signaling in adjuvant-induced arthritis rats and inhibits inflammatory response, ameliorating the severity of the arthritis model [ 46 ]. Hence, a growing number of evidences suggest that the Nrf-2 activation induced by H 2 S is also responsible for its anti-inflammatory effects [ 46 , 63 , 64 ]. In our study, we observed for the first time that the administration of a slow-releasing H 2 S donor in the joint induces the expression of Nrf-2 in the cartilage and that this event could contribute to the attenuation of the expression of pro-inflammatory markers detected in our model and subsequently to its pathogenesis.…”

Could Oxidative Stress Regulate the Expression of MicroRNA-146a and MicroRNA-34a in Human Osteoarthritic Chondrocyte Cultures?

“…Under normal conditions, the harmful production of endogenous ROS is balanced by the antioxidant defence system including enzymes like SOD-2, CAT and GPx, to decrease oxidative stress. SOD-2 or manganese-dependent (Mn)-SOD represents one of the three SOD family members; it is located in the mitochondrial matrix of the cells and catalyzes the dismutation of superoxide anion in O 2 and H 2 O 2 , which is then turned in water, to CAT and GPx [ 29 , 30 ]. In vivo and in vitro studies have demonstrated the reduction in expression and activity of these stress-related enzymes in OA chondrocytes, leading to the loss of their ability to scavenge ROS.…”

Pharmacological Investigation of the Anti-Inflammation and Anti-Oxidation Activities of Diallyl Disulfide in a Rat Emphysema Model Induced by Cigarette Smoke Extract

“…Garlic possesses nutritional values and medicinal characteristics. Diallyl disulfide (DADS) is the main organosulfur ingredient in garlic, and has shown diverse pharmacological properties such as anti-inflammation [ 14 , 15 ], anti-oxidation [ 16 , 17 , 18 , 19 , 20 ] and immune regulation [ 21 ]. The anti-inflammatory effects of DADS observed can be attributed to its ability to decrease inflammatory mediators by inhibiting NF-κB translocation and i-κB phosphorylation, as well as suppressing the expression of mRNA for IL-1β and TNF-α [ 22 , 23 ].…”