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, wher...

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Autores principales:	Lanzhou Li, Di Wang, Xueju Wang, Ruifeng Bai, Chunyu Wang, Yin Gao, Tassos Anastassiades
Formato:	article
Lenguaje:	EN
Publicado:	Taylor & Francis Group 2019
Materias:	cytokines ros n-acylation Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/1a2d463efdd14d069314c00738757393
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spelling	oai:doaj.org-article:1a2d463efdd14d069314c007387573932021-11-17T14:21:56ZN-Butyrylated hyaluronic acid ameliorates gout and hyperuricemia in animal models1388-02091744-511610.1080/13880209.2019.1672755https://doaj.org/article/1a2d463efdd14d069314c007387573932019-01-01T00:00:00Zhttp://dx.doi.org/10.1080/13880209.2019.1672755https://doaj.org/toc/1388-0209https://doaj.org/toc/1744-5116Context: 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.Lanzhou LiDi WangXueju WangRuifeng BaiChunyu WangYin GaoTassos AnastassiadesTaylor & Francis Grouparticlecytokinesrosn-acylationTherapeutics. PharmacologyRM1-950ENPharmaceutical Biology, Vol 57, Iss 1, Pp 717-728 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	cytokines ros n-acylation Therapeutics. Pharmacology RM1-950
spellingShingle	cytokines ros n-acylation Therapeutics. Pharmacology RM1-950 Lanzhou Li Di Wang Xueju Wang Ruifeng Bai Chunyu Wang Yin Gao Tassos Anastassiades N-Butyrylated hyaluronic acid ameliorates gout and hyperuricemia in animal models
description	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.
format	article
author	Lanzhou Li Di Wang Xueju Wang Ruifeng Bai Chunyu Wang Yin Gao Tassos Anastassiades
author_facet	Lanzhou Li Di Wang Xueju Wang Ruifeng Bai Chunyu Wang Yin Gao Tassos Anastassiades
author_sort	Lanzhou Li
title	N-Butyrylated hyaluronic acid ameliorates gout and hyperuricemia in animal models
title_short	N-Butyrylated hyaluronic acid ameliorates gout and hyperuricemia in animal models
title_full	N-Butyrylated hyaluronic acid ameliorates gout and hyperuricemia in animal models
title_fullStr	N-Butyrylated hyaluronic acid ameliorates gout and hyperuricemia in animal models
title_full_unstemmed	N-Butyrylated hyaluronic acid ameliorates gout and hyperuricemia in animal models
title_sort	n-butyrylated hyaluronic acid ameliorates gout and hyperuricemia in animal models
publisher	Taylor & Francis Group
publishDate	2019
url	https://doaj.org/article/1a2d463efdd14d069314c00738757393
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N-Butyrylated hyaluronic acid ameliorates gout and hyperuricemia in animal models

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