Department of Hand and Foot Micro Burn Plastic Surgery, 3201 Hospital, Hanzhong, People's Republic of China.
Department of Neurosurgery, The First Hospital of Kunming, Kunming, People's Republic of China.
Drug Des Devel Ther. 2023 Feb 18;17:519-534. doi: 10.2147/DDDT.S391606. eCollection 2023.
Bone dysfunction is a crucial problem that occurs during rheumatoid arthritis (RA) disease. Osteoclast plays a significant role in bone resorption and osteoclast differentiation and its enhancement of bone destruction. Edaravone remarkably exhibited free radical scavenging and anti-inflammatory effects. The objective of the current investigation is to comfort the inhibitory effect of Edaravone (ED) against complete Freund adjuvant (CFA) rat model via inhibition of angiogenesis and inflammation.
Subcutaneous injection of CFA (1%) was used to induce arthritis; the rats were divided into different groups and received the oral administration of ED. Paw edema, body weight, and arthritis score were regularly estimated. Biochemical parameters were estimated, respectively. We also estimate the level of hypoxia-inducible factor-1α (HIF-1α), angiopoietin 1 (ANG-1), and vascular endothelial growth factor (VEGF). We also checked into how ED affected the differentiation of osteoclasts utilising a co-culture system with monocytes and synovial fibroblasts in arthritis rats.
ED treatment significantly (P<0.001) suppressed the arthritis score and paw edema and improved the body weight. ED treatment significantly (P<0.001) altered the antioxidant parameters and pro-inflammatory cytokines: inflammatory mediator nuclear kappa B factor (NF-κB), cyclooxygenase-2 (COX-2), and prostaglandin E (PGE), respectively. Furthermore, ED treatment significantly (P<0.001) suppressed the level of ANG-1, HIF-1α, and VEGF, respectively. The results suggest that ED suppressed osteoclast differentiation and also decreased the level of cytokines and osteopontin (OPN), receptor activator for nuclear factor-κ B Ligand (RANKL) and macrophage colony stimulating factor (M-CSF) in the co-culture supernatant of monocytes and synovial fibroblasts.
Edaravone could mitigate CFA via inhibiting angiogenesis and inflammatory reactions, which may be linked with the HIF-1α-VEGF-ANG-1 axis and also enhance the bone destruction of murine arthritis via suppression of osteoclast differentiation and inflammatory reaction.
骨功能障碍是类风湿关节炎（RA）疾病中发生的一个关键问题。破骨细胞在骨吸收和破骨细胞分化及其增强骨破坏中起重要作用。依达拉奉显著表现出自由基清除和抗炎作用。本研究的目的是通过抑制血管生成和炎症来缓解依达拉奉（ED）对完全弗氏佐剂（CFA）大鼠模型的抑制作用。
皮下注射 CFA（1%）诱导关节炎；将大鼠分为不同组，并给予 ED 口服给药。定期评估爪肿胀、体重和关节炎评分。分别估计生化参数。我们还评估了缺氧诱导因子-1α（HIF-1α）、血管生成素 1（ANG-1）和血管内皮生长因子（VEGF）的水平。我们还检查了 ED 如何通过关节炎大鼠的单核细胞和滑膜成纤维细胞共培养系统影响破骨细胞的分化。
ED 治疗显著（P<0.001）抑制关节炎评分和爪肿胀，改善体重。ED 治疗显著（P<0.001）改变抗氧化参数和促炎细胞因子：核因子 kappa B 因子（NF-κB）、环氧化酶-2（COX-2）和前列腺素 E（PGE）。此外，ED 治疗显著（P<0.001）抑制 ANG-1、HIF-1α 和 VEGF 的水平。结果表明，ED 抑制破骨细胞分化，并降低单核细胞和滑膜成纤维细胞共培养上清液中细胞因子和骨桥蛋白（OPN）、核因子-κ B 配体受体激活剂（RANKL）和巨噬细胞集落刺激因子（M-CSF）的水平。
依达拉奉可以通过抑制血管生成和炎症反应来减轻 CFA，这可能与 HIF-1α-VEGF-ANG-1 轴有关，并通过抑制破骨细胞分化和炎症反应来增强鼠关节炎的骨破坏。
