l-Glutathione enhances antioxidant capacity of hyaluronic acid and modulates expression of pro-inflammatory cytokines in human fibroblast-like synoviocytes

Abstract

Intra-articular injection of hyaluronic acid (HA) has been widely accepted for the treatment of osteoarthritis (OA) in early stage. l-Glutathione (GSH), an antioxidant, has an anti-inflammatory effect on protecting cells from reactive oxygen species and reactive nitrogen species (ROS/RNS). In this study, the therapeutic effects of HA (0.1%) supplemented with GSH (0, 5, 10, and 20% in weight ratios to HA) on human fibroblast-like synoviocytes (FLSs) were evaluated. The results showed that cell morphology and glycosaminoglycan production of FLSs were not changed under treatments. However, the addition of HA + 20% GSH significantly decreased cell survival (p < 0.001) relative to other groups. Relative to un-stimulated FLSs, interleukin-1 beta (IL-1β) stimulation significantly decreased the total antioxidant capacity (p < 0.001) of cells. The antioxidant capacity was restored and the intracellular ROS/RNS was decreased in HA or HA + GSH-treated FLSs. Real-time PCR analysis revealed the mRNA levels of IL-1β, tumor necrosis factor-alpha, and matrix metalloproteinase-3 were down-regulated significantly (all p < 0.05) when FLSs cultured in HA or HA + GSH. IL-6 mRNA expressions were down-regulated significantly in HA and HA + 5% GSH groups (both p < 0.05) but up-regulated when HA supplemented with 10% and 20% GSH (both p < 0.01). In addition, the protein levels of IL-1β were further decreased with significant differences (both p < 0.05) in the HA + 10% GSH and HA + 20% GSH groups when compared to FLSs cultured in normal medium. In conclusion, HA supplemented with GSH improves antioxidant capacity and modulates pro-inflammatory cytokines expressions in FLSs. GSH has the potential to augment the effect of viscosupplementation using HA on OA patients. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 2071-2079, 2016.

Bacterial hyaluronic acid production through an alternative extraction method and its characterization

“…However, TNF‐alpha was found to be higher in the range of 7–12% than the control group. Contrary to our results, Neuman and colleagues, and Yang and coworkers determined that HA downregulated pro‐inflammatory cytokine. In the literature, it also is suggested that low molecular weight HA stimulates pro‐inflammatory cytokines and also NOS .…”

Glycosaminoglycan and Proteoglycan Biotherapeutics in Articular Cartilage Protection and Repair Strategies: Novel Approaches to Visco‐supplementation in Orthobiologics

“…[391] A systematic review, which included data from six randomized controlled trials comparing the effectiveness of PRP with other intra-articular injections, exercise, or analgesia for a minimum of 6 months PRP produced statistically significant improvements in WOMAC scores for up to 12 months. [393][394][395] www.advancedsciencenews.com www.advtherap.com HA hydrogel n/a Dexamethasone Cortocosteroid [310] Adant (Suprahyal) 500-1000 Tenoxicam NSAID [311] Variofill (Adoderm, Langenfeld, Gmbh) HMWCR Diclofenac Sodium clodronate Triamcinolone acetonide Ropivacaine HCl NSAID DMOAD Cortocosteroid Anaesthetic [312] [ 313] Hydros, Hydros-TA HMW Triamcinolone acetonide Cortocosteroid [314] Cingal 1900 Triamcinolone acetonide Cortocosteroid [315] Hylan GF-20 HMWCR Triamcinolone acetonide Cortocosteroid [316] HA solution 800 Mannitol Anti-oxidant [317] Go-on matrix Ostenil Plus 1500 Mannitol Anti-oxidant [320] Happyvix 1500 Mannitol Anti-oxidant [320] Happycross 1500 Mannitol Anti-oxidant [320] Synolis V-A 2000 Sorbitol Anti-oxidant [320] HA 4AR conjugate 2200 4 aminoresorcinol Anti-oxidant [321] Ostenil 1000-2000 l-glutathione Anti-oxidant [322] Arthrum HCS 2800 CS GAG [320] Surgical Syonium 2800 CS GAG [320] HA-sCT conjugate 200 Salmon calcitonin DMOAD [323] HA ADAMTS inhibitor n/a ADAMTS inhibitor DMOAD [324] HA hydrogel 60-120 Doxycycline DMOAD [296] Hanox Hanox M-XL 1500 n/a Cortivazol Triamcinolone hexacetonide Mannitol + lidocaine clorhydrate Cortocosteroid Cortocosteroid Anti-oxidant + local anaesthetic [325] n/a, not available; HMW, high molecular weight; HMWCR, high molecular weight cross-linked. [393][394][395] www.advancedsciencenews.com www.advtherap.com HA hydrogel n/a Dexamethasone Cortocosteroid [310] Adant (Suprahyal) 500-1000 Tenoxicam NSAID [311] Variofill (Adoderm, Langenfeld, Gmbh) HMWCR Diclofenac Sodium clodronate Triamcinolone acetonide Ropivacaine HCl NSAID DMOAD Cortocosteroid Anaesthetic …”

Hyaluronic acid filler combined with antioxidants for infraorbital rejuvenation: Report of two cases

“…HA supplemented with glutathione exhibits improved antioxidant capacity and modulates proinflammatory cytokine expression in human fibroblast‐like synoviocytes. Glutathione has the potential to augment the effect of visco‐supplementation mediated by HA in patients with osteoarthritis (Yang, Wu, Chen, Sumi, & Huang, ). Amino acids are required to build dermal extracellular matrix proteins, mainly collagens, and a number of vitamins and minerals have important functions that are relevant to the skin aging process (Prikhnenko, ).…”