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

Abstract

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 lg) 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 ¼ 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 lg) demonstrated a strong antiinflammatory effect by reducing the degree of articular swelling and the serum levels of IL-1b, IL-8, IFN-c, and MCP-1 by 5.56%, 6.55%, 15.58% and 33.18%. In the hyperuricemic mouse model, lower dosage BHA (10 lg) 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.

Hyaluronic Acid: A Key Ingredient in the Therapy of Inflammation

“…Gout is a metabolic disorder of the purine accompanied by high levels of uric acid (UA) in the blood and the precipitation of sodium monourate crystals (monosodium urate (MSU)) in the joints and tissues. In the absence of treatment, progressive deterioration of the tissues and bones of the joints can occur, causing chronic synovitis, bone erosions, damage to the cartilage and tophi formation [114,115]. The work by Wang et al, shows that N-butyrylated HA (BHA) has an anti-inflammatory effect, leading to a reduction in joint swelling and a reduction in serum levels of IL-1β, IL-8, gamma interferon (IFN-γ) and monocyte chemoattractant protein 1 (MCP-1).…”

“…The intraperitoneal injection of BHA suppressed UA production, reducing the activity of xanthine oxidase (XO, which catalyses UA production). BHA has been shown to exhibit anti-inflammatory, antioxidant and antihyperuricemic effects in vivo [115].…”

Eggshell Membrane Ameliorates Hyperuricemia by Increasing Urate Excretion in Potassium Oxonate-Injected Rats

“…Previous studies reported that glucosamine and chondroitin have demonstrated anti-inflammatory and anti-osteoarthritic effects [31,32]. Hyaluronic acid exhibited anti-inflammatory and antihyperuricemic effects in monosodium urate crystal-induced animal models for acute gouty arthritis and hyperuricemia [33]. The results of these studies show the potential usefulness of these components to prevent and treat hyperuricemia.…”

Persistent Purine Metabolic Abnormality Induces the Aggravation of Visceral Inflammation and Intestinal Microbiota Dysbiosis in Magang Goose

“…Studies have shown that gout caused by urate was mediated by the TLR4/NF-κB signaling pathway, and the IL-1β released was linearly related to it ( 20 , 21 ). Destruction of the intestinal barrier induced the translocation of gut-derived LPS from the gut to the liver, which increases the expression of inflammatory factors such as IL-1β and TNF-α in the liver ( 22 , 23 ).…”