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.