Yuan Qing, Zhao Yao, Cai Pengju, He Zhesheng, Gao Fuping, Zhang Jinsong, Gao Xueyun
Department of Chemistry and Chemical Engineering, Beijing University of Technology, Beijing 100124, China.
Center of Excellence for Environmental Safety and Biological Effects, Beijing University of Technology, Beijing 100124, China.
ACS Omega. 2019 Aug 16;4(9):14092-14099. doi: 10.1021/acsomega.9b02003. eCollection 2019 Aug 27.
Chronic inflammation and progressive bone damage in joints are two main pathological features of rheumatoid arthritis (RA). We have synthesized a gold cluster with glutathione (AuSG) (named GA) that can effectively suppress both inflammation and bone damage in collagen-induced arthritis (CIA) in rats. Thus, gold clusters showed great potential for the therapy of RA. However, the optimal therapeutic dose remaining has to be determined. Therapeutic effect and safety are largely relying on drug dosage. Specifying the dose-dependent effects of GA on both therapy and biosafety can facilitate its clinical transformation research. Therefore, in this study, we comprehensively evaluated the dose-dependent efficacy of GA on the 30-day toxicity and RA treatment in rats. Results showed that continuous intraperitoneal injection of GA at a dose of 15 mg/kg (Au content) for 30 days resulted in slight hematological abnormalities and increases on organ coefficients of kidney and adrenal gland, while 10 mg Au/kg did not cause any obvious toxicity and side effects. In the treatment of CIA rats, only when the dose of GA reached 5 mg Au/kg, the symptoms of RA could be significantly improved. With regard to the histopathological analysis, although a lower dose of GA can suppress inflammation and bone damage to some extent, only the 5 mg Au/kg treatment could restore them to a state close to the normal control group. Therefore, we infer that 5 mg Au/kg is the optimal dose of GA for RA therapy in rats, which provides a theoretical basis for further preclinical research.
关节中的慢性炎症和进行性骨损伤是类风湿性关节炎（RA）的两个主要病理特征。我们合成了一种与谷胱甘肽结合的金簇（AuSG）（命名为GA），它可以有效抑制大鼠胶原诱导性关节炎（CIA）中的炎症和骨损伤。因此，金簇在RA治疗中显示出巨大潜力。然而，仍需确定最佳治疗剂量。治疗效果和安全性在很大程度上取决于药物剂量。明确GA在治疗和生物安全性方面的剂量依赖性效应有助于其临床转化研究。因此，在本研究中，我们全面评估了GA对大鼠30天毒性和RA治疗的剂量依赖性疗效。结果表明，连续30天腹腔注射15mg/kg（金含量）的GA会导致轻微的血液学异常以及肾脏和肾上腺器官系数增加，而10mg金/kg不会引起任何明显的毒性和副作用。在治疗CIA大鼠时，只有当GA剂量达到5mg金/kg时，RA症状才能得到显著改善。关于组织病理学分析，虽然较低剂量的GA可以在一定程度上抑制炎症和骨损伤，但只有5mg金/kg的治疗能将它们恢复到接近正常对照组的状态。因此，我们推断5mg金/kg是GA治疗大鼠RA的最佳剂量，这为进一步的临床前研究提供了理论依据。
