Dose-Dependent Efficacy of Gold Clusters on Rheumatoid Arthritis Therapy

Abstract

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 (Au29SG27) (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.