Radiation Biology Department, National Center for Radiation Research and Technology (NCRRT), Egyptian Atomic Energy Authority, Cairo 11787, Egypt.
Radiation Biology Department, National Center for Radiation Research and Technology (NCRRT), Egyptian Atomic Energy Authority, Cairo 11787, Egypt.
Int Immunopharmacol. 2022 Oct;111:109068. doi: 10.1016/j.intimp.2022.109068. Epub 2022 Aug 6.
Prodigiosin (PDG) is a microbial red dye with antioxidant and anti-inflammatory properties, although its effect on rheumatoid arthritis (RA) remains uncertain. Also, multiple doses of low dose γ- radiation (LDR) have been observed to be as a successful intervention for RA. Thus, the purpose of this study was to investigate the ameliorative potential of PDG and/or LDR on adjuvant-induced arthritis (AIA) in rats.
The anti-inflammatory and anti-arthritic effects of PDG and/or LDR were examined in vitro and in vivo, respectively. In the AIA model, the arthritic indexes, paw swelling degrees, body weight gain, and histopathological assessment in AIA rats were assayed. The impact of PDG (200 µg/kg; p.o) and/or LDR (0.5 Gy) on the levels of pro- and anti-inflammatory cytokines (IL-1β, TNF-α, IL-6, IL-18, IL-17A, and IL-10) as well as the regulation of osteoprotegrin (OPG)/ receptor activator of nuclear factor κB ligand (RANKL)/ nuclear factor-κB (NF-κB)/MMP-13 pathways was determined. Methotrexate (MTX; 0.05 mg/kg; twice/week, i.p) was administered concurrently as a standard anti-arthritic drug.
PDG and/or LDR markedly diminished the arthritic indexes, paw edema, weigh loss in AIA rats, alleviated the pathological alterations in joints, reduced the levels of pro-inflammatory cytokines IL-1β, TNF-α, IL-6, IL-18, IL-17A, and RANKL in serum and synovial tissues, while increasing anti-inflammatory cytokines IL-10 and OPG levels. Moreover, PDG and/or LDR down-regulated the expression of RANKL, NF-κBp65, MMP13, caspase-3, and decreased the RANKL/OPG ratio, whereas OPG and collagen II were enhanced in synovial tissues.
PDG and/or LDR exhibited obvious anti-RA activity on AIA.
灵菌红素（PDG）是一种具有抗氧化和抗炎特性的微生物红色染料，但它对类风湿关节炎（RA）的影响尚不确定。此外，已观察到多次低剂量γ辐射（LDR）治疗可成功干预 RA。因此，本研究旨在探讨 PDG 和/或 LDR 对佐剂诱导关节炎（AIA）大鼠的改善潜力。
分别在体外和体内研究 PDG 和/或 LDR 的抗炎和抗关节炎作用。在 AIA 模型中，测定 AIA 大鼠的关节炎指数、爪肿胀程度、体重增加和组织病理学评估。检测 PDG（200μg/kg；po）和/或 LDR（0.5Gy）对促炎和抗炎细胞因子（IL-1β、TNF-α、IL-6、IL-18、IL-17A 和 IL-10）水平的影响，以及对核因子κB（NF-κB）/基质金属蛋白酶 13（MMP-13）通路的调节。甲氨蝶呤（MTX；0.05mg/kg；每周两次，ip）作为标准抗关节炎药物同时给药。
PDG 和/或 LDR 显著降低 AIA 大鼠的关节炎指数、爪肿胀、体重减轻，缓解关节病理改变，降低血清和滑膜组织中促炎细胞因子 IL-1β、TNF-α、IL-6、IL-18、IL-17A 和 RANKL 水平，增加抗炎细胞因子 IL-10 和 OPG 水平。此外，PDG 和/或 LDR 下调 RANKL、NF-κBp65、MMP13、caspase-3 的表达，降低 RANKL/OPG 比值，同时增强滑膜组织中的 OPG 和胶原 II。
PDG 和/或 LDR 对 AIA 具有明显的抗 RA 活性。
