N-Butyrylated hyaluronic acid ameliorates gout and hyperuricemia in animal models.

Context: Hyaluronic acid (HA) plays critical roles in the structural skeleton, joint lubrication, renal function and cell signaling. We previously showed that partially N-butyrylated, low molecular weight, hyaluronic acid (BHA) exhibited an anti-inflammatory effect in cultured human macrophage, where inflammation was induced either by a TL-4 agonist or the low molecular weight HA itself, in dose-dependent fashion. Objectives: To investigate the anti-inflammatory, antioxidative, and antihyperuricemic effects of BHA using animal models of acute gouty arthritis and hyperuricemia. Materials and methods: The anti-inflammatory effect of articular BHA (10 and 50 μg) injections was evaluated by measuring joint swelling and the serum levels of inflammatory cytokines in a model of acute gouty arthritis induced by intra-articular injection of monosodium urate crystals in Wistar rats (n = 10/group), in comparison to the control group with saline injection. Antioxidative and antihyperuricemic activities were investigated using intraperitoneal injections of oteracil potassium and yeast extract hyperuricemic Balb/C mice, which were treated with intraperitoneal injection of BHA at day 6-8 in the model. Results: In the gouty arthritis rat model, BHA at a higher dosage (50 μg) demonstrated a strong anti-inflammatory effect by reducing the degree of articular swelling and the serum levels of IL-1β, IL-8, IFN-γ, and MCP-1 by 5.56%, 6.55%, 15.58% and 33.18%. In the hyperuricemic mouse model, lower dosage BHA (10 μg) was sufficient to provide antioxidative activities by significantly decreasing the ROS levels in both serum and liver by 14.87% and 8.04%, while improving liver SOD by 12.77%. Intraperitoneal injection of BHA suppressed uric acid production through reducing liver XO activity by 19.78% and decreased the serum uric acid level in hyperuricemic mice by 30.41%. Conclusions: This study demonstrated for the first time that BHA exhibits anti-inflammatory, antioxidative and antihyperuricemic effects in vivo, suggesting a potential therapeutic application of BHA in gouty arthritis and hyperuricemia.