Journal of Peking University (Health Sciences) ›› 2021, Vol. 53 ›› Issue (4): 716-720. doi: 10.19723/j.issn.1671-167X.2021.04.016

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Effect of rebamipide on the acute gouty arthritis in rats induced by monosodium urate crystals

WANG Gui-hong(),ZUO Ting,LI Ran,ZUO Zheng-cai   

  1. Department of Rheumatology and Immunology, Anqing Hospital of Anhui Medical University, Anqing 246000, Anhui, China
  • Received:2019-08-23 Online:2021-08-18 Published:2021-08-25
  • Contact: Gui-hong WANG E-mail:wgh-70@sohu.com
  • Supported by:
    Anqing Medical Technology Project(2018Z2003)

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Abstract:

Objective: To investigate the role of rebamipide in the treatment of acute gout arthritis rats induced by monosodium urate (MSU) crystal. Methods: Forty-two male rats were randomly divided into three groups (n=14). Group A was treated with oral rebamipide, group B with oral colchicine, and group C with oral placebo. The rats were monitored for the induction of arthritis with clinical manifestations and pathological changes, and the levels of interleukin (IL)-1β、IL-6、IL-10, and tumor necrosis factor (TNF)-α in serum were measured. Results: In group C, the clinical score and swelling index reached the maximum in 24 h, and then gradually decreased to 72 h. After 24 h of model induced, the clinical scores in group C were significantly higher than those in group A and group B [2 (1-3) vs. 0 (0-1) vs. 1 (0-2), P<0.01], the swelling indexes in group C were significantly higher than those in group A and group B [0.36 (0.16-0.52) vs. 0.11 (0-0.20) vs. 0.12 (0-0.16), P<0.01]. Histologically, after 24 h of model induced, there was a large number of neutrophil infiltration in the synovium of group C [scale score: 4 (2-4)], and there was no significant inflammatory cell infiltration in group A [1 (0-2)] and group B [1 (0-2)], the difference was statistically significant (P<0.001). After 24 h of model induced, the levels of IL-1β, IL-6, IL-10, and TNF-α in serum of group C were significantly higher than those in group A and B [IL-1β: (41.86±5.72) vs. (27.35±7.47) vs. (27.76±5.28) ng/L, IL-6: (1 575.55±167.11) vs. (963.53±90.22) vs. (964.08±99.31) ng/L, IL-10: (37.96±3.76) vs. (21.68±4.83) vs. (16.20±2.49) ng/L, TNF-α: (21.32±1.34) vs. (15.82±2.54) vs. (17.35±7.47) μg/L, P<0.001]. Conclusion: Rebamipide has a protective effect on acute gout arthritis rats induced by MUS crystals.

Key words: Gouty arthritis, Rebamipide, Animal models, Rats

CLC Number: 

  • R589.7

Figure 1

Rat model of acute gout arthritis induced by monosodium urate crystals"

Figure 2

Clinical score and swelling index of the three rat groups at the five time points after model induced"

Table 1

Comparison of serum cytokines, clinical manifestations and histological changes in three rat groups at 24 h after modeling"

Items Rebamipide group Colchicine group Placebo group F value P value
IL-1β/(ng/L) 27.35±7.47 27.76±5.28 41.86±5.72 14.06 <0.001
IL-6/(ng/L) 963.53±90.22 964.08±99.31 1 575.55±167.11 65.18 <0.001
IL-10/(ng/L) 21.68±4.83 16.20±2.49 37.96±3.76 35.60 <0.001
TNF-α/(μg/L) 15.82±2.54 17.35±7.47 21.32±1.34 15.63 <0.001
Clinical score 0 (0-1) 1 (0-2) 2 (1-3) 0.008
Swelling index 0.11 (0-0.20) 0.12 (0-0.16) 0.36 (0.16-0.52) 0.005
Infiltration of inflammatory cells 1 (0-2) 1 (0-2) 4 (2-4) <0.001

Figure 3

The infiltration of inflammatory cells in ankle joint synovium at the different time points of the three rat groups (HE ×400)"

Figure 4

Changes of serum IL-1β, IL-6, IL-10, and TNF-α levels in three rat groups at the 4 time points after induced by MSU crystals IL, interleukin; TNF, tumor necrosis factor."

[1] 路杰, 崔凌凌, 李长贵, 等. 原发性痛风流行病学研究进展 [J]. 中华内科杂志, 2015, 54(3):244-247.
[2] 中华医学会风湿病学分会. 2016中国痛风诊疗指南 [J]. 中华内科杂志, 2016, 55(11):892-899.
[3] Kim SK, Choe JY, Park KY. Rebamipide suppresses monosodium urate crystal-induced interleukin-1β production through regulation of oxidative stress and Caspase-1 in THP-1 cells [J]. Inflammation, 2016, 39(1):473-482.
doi: 10.1007/s10753-015-0271-5
[4] Moon SJ, Woo YJ, Jeong JH, et al. Rebamipide attenuates pain severity and cartilage degeneration in a rat model of osteoarthritis by downregulating oxidative damage and catabolic activity in chondrocytes [J]. Osteoarthritis Cartilage, 2012, 20(11):1426-1438.
doi: 10.1016/j.joca.2012.08.002
[5] Kohashi M, Ishimaru N, Arakaki R, et al. Effective treatment with oral administration of rebamipide in a mouse model of Sjögren’s syndrome [J]. Arthritis Rheum, 2008, 58(2):389-400.
doi: 10.1002/(ISSN)1529-0131
[6] Coderre TJ, Wall PD. Ankle joint urate arthritis (AJUA) in rats: an alternative animal model of arthritis to that produced by Freund’s adjuvant [J]. Pain, 1987, 28(3):379-393.
pmid: 3574965
[7] Park JS, Oh Y, Park O, et al. PEGylated TRAIL ameliorates experimental inflammatory arthritis by regulation of Th17 cells and regulatory T cells [J]. J Control Release, 2017, 267:163-171.
doi: 10.1016/j.jconrel.2017.10.004
[8] Hartmann P, Szabó A, Eros G, et al. Anti-inflammatory effects of phosphatidylcholine in neutrophil leukocyte-dependent acute arthritis in rats [J]. Eur J Pharmacol, 2009, 622(1/3):58-64.
doi: 10.1016/j.ejphar.2009.09.012
[9] Tramontini N, Huber C, Liu-Bryan R, et al. Central role of complement membrane attack complex in monosodium urate crystal-induced neutrophilic rabbit knee synovitis [J]. Arthritis Rheum, 2004, 50(8):2633-2639.
doi: 10.1002/(ISSN)1529-0131
[10] Martinon F. Mechanisms of uric acid crystal-mediated autoinflammation [J]. Immunol Rev, 2010, 233(1):218-232.
doi: 10.1111/j.0105-2896.2009.00860.x pmid: 20193002
[11] Zhang Y, Zheng Y. Effects and mechanisms of potent caspase 1 inhibitor VX765 treatment on collagen-induced arthritis in mice [J]. Clin Exp Rheumatolm, 2016, 34(1):111-118.
[12] Jhang JJ, Lu CC, Yen GC. Epigallocatechin gallate inhibits urate crystals-induced peritoneal inflammation in C57BL/6 mice [J]. Mol Nutr Food Res, 2016, 60(10):2297-2303.
doi: 10.1002/mnfr.v60.10
[13] Zhang S, Qing Q, Bai Y, et al. Rebamipide helps defend against nonsteroidal anti-inflammatory drugs induced gastroenteropathy: A systematic review and meta-analysis [J]. Dig Dis Sci, 2013, 58(7):1991-2000.
doi: 10.1007/s10620-013-2606-0
[14] Choe JY, Park KY, Lee SJ, et al. Rebamipide inhibits tumor necrosis factor-α-induced interleukin-8 expression by suppressing the NF-κB signal pathway in human umbilical vein endothelial cells [J]. Inflamm Res, 2010, 59(12):1019-1026.
doi: 10.1007/s00011-010-0221-5
[15] Kim H, Seo JY, Kim KH. Inhibition of lipid peroxidation, NFkappaB activation and IL-8 production by rebamipide in Helicobacter pylori-stimulated gastric epithelial cells [J]. Dig Dis Sci, 2000, 45(3):621-628.
doi: 10.1023/A:1005474013988
[16] Funahashi Y, Yoshida M, Yamamoto T, et al. Intravesical application of rebamipide suppresses bladder inflammation in a rat cystitis model [J]. J Urol, 2014, 191(4):1147-1152.
doi: 10.1016/j.juro.2013.11.026 pmid: 24262494
[17] Suzuki Y, Hasegawa M, Matsui Y, et al. Intra-articular injection of rebamipide prevents articular cartilage degeneration in murine post-traumatic osteoarthritis models [J]. Mod Rheumatol, 2020, 30(4):765-772.
doi: 10.1080/14397595.2019.1641912
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