Biomaterial Database

Dimethyl fumarate attenuates MSU-induced gouty arthritis by inhibiting NLRP3 inflammasome activation and oxidative stress. 2023

Y Cao, and Y Hu, and X-F Jin, and Y Liu, and J-M Zou

Department of Rheumatology, The First People's Hospital of LouDi, LouDi, Hunan, China. zjm19900222@126.com.

Dimethyl fumarate (DMF) has shown anti-inflammatory and antioxidant activities. However, the effects of DMF on gouty arthritis remain elusive, and the underlying mechanism is not understood. In this study, we aim to investigate the role of DMF in gouty arthritis. Mice were gavage with DMF for consecutive 7 days at two different doses (10 mg/kg/day or 30 mg/kg/day, once daily) in advance and then monosodium sodium urate (MSU) was injected into their joint to establish an acute gout mice model. The pain and swelling of the hind paw in mice were determined. The production of pro-inflammatory cytokine in the paw tissues was assessed by Elisa and the inflammatory infiltration of the joint was determined by hematoxylin and eosin (H&E) staining. The activity of superoxide dismutase (SOD) and the content of malondialdehyde (MDA) in the tissues were measured by commercial kits. In addition, the expression of nuclear factor kappa B (NF-κB) and NACHT, LRR, and PYD domains-containing protein 3 (NLRP3) inflammasome and downstream genes were detected by PCR and Western blot. Furthermore, LPS-primed murine macrophages Raw 264.7 cells were treated with different concentrations of DMF (2 μM, 5 μM, 10 μM) for 2 h, and then challenged with MSU (200 μg/mL) for other 12 h to observe the effect of DMF on cell viability via cell counting kit-8 (CCK-8) assay and lactate dehydrogenase (LDH) levels in the supernatant of culture medium. Immunofluorescent staining was used to detect the NLRP3 inflammasome activation and reactive oxygen species (ROS) production in vitro. Caspase-1 activity was measured by corresponding assay kits both in vivo and in vitro. DMF attenuated pain and swelling in MSU-induced gout mice by decreasing pro-inflammatory cytokine production and inflammatory cell infiltration, as well as improved oxidative stress. Moreover, DMF inhibited the activation of NF-κB and NLRP3 inflammasome and subsequent expression of caspase-1, interleukin-1β (IL-1β), and IL-18 at both mRNA and protein levels. Meanwhile, DMF suppressed NLRP3 inflammasome expression and ROS production in LPS and MSU-stimulated Raw 264.7 cells, thereby protecting the cells from inflammatory injury. DMF serves as a new approach for the treatment of MSU-induced gouty arthritis by suppressing NLRP3 inflammasome activation and oxidative stress.

UI	MeSH Term	Description	Entries
D008070	Lipopolysaccharides	Lipid-containing polysaccharides which are endotoxins and important group-specific antigens. They are often derived from the cell wall of gram-negative bacteria and induce immunoglobulin secretion. The lipopolysaccharide molecule consists of three parts: LIPID A, core polysaccharide, and O-specific chains (O ANTIGENS). When derived from Escherichia coli, lipopolysaccharides serve as polyclonal B-cell mitogens commonly used in laboratory immunology. (From Dorland, 28th ed)	Lipopolysaccharide,Lipoglycans
D010146	Pain	An unpleasant sensation induced by noxious stimuli which are detected by NERVE ENDINGS of NOCICEPTIVE NEURONS.	Suffering, Physical,Ache,Pain, Burning,Pain, Crushing,Pain, Migratory,Pain, Radiating,Pain, Splitting,Aches,Burning Pain,Burning Pains,Crushing Pain,Crushing Pains,Migratory Pain,Migratory Pains,Pains, Burning,Pains, Crushing,Pains, Migratory,Pains, Radiating,Pains, Splitting,Physical Suffering,Physical Sufferings,Radiating Pain,Radiating Pains,Splitting Pain,Splitting Pains,Sufferings, Physical
D006073	Gout	Metabolic disorder characterized by recurrent acute arthritis, hyperuricemia and deposition of sodium urate in and around the joints, sometimes with formation of URIC ACID calculi.	Gouts
D000069462	Dimethyl Fumarate	A fumarate derivative that is used as a DERMATOLOGIC AGENT in the treatment of PSORIASIS and SKIN DISEASES. It also may be used as an IMMUNOSUPPRESSIVE AGENT in the treatment of MULTIPLE SCLEROSIS.	2-butenedioic acid, (2E)-, dimethyl ester,BG 00012,BG 12 compound,BG-00012,BG-12 compound,BG00012,BG12 compound,Dimethylfumarate,FAG 201,FAG-201,FAG201,Fumaderm,Tecfidera,00012, BG,12 compound, BG,201, FAG,Fumarate, Dimethyl,compound, BG 12,compound, BG12
D000071199	NLR Family, Pyrin Domain-Containing 3 Protein	An NLR protein that contains an N-terminal PYRIN DOMAIN and ATP-binding site and 9 C-terminal LEUCINE-rich repeats; it is expressed primarily by MACROPHAGES. It is a core component of the INFLAMMASOME and directs its assembly in response to pathogen infection and damage-associated stimuli. Mutations in the NLRP3 gene are associated with FAMILIAL COLD AUTOINFLAMMATORY SYNDROME.	Cold Autoinflammatory Syndrome 1 Protein,NACHT, LRR and PYD Domains-Containing Protein 3,NLRP3 Protein,NACHT, LRR and PYD Domains Containing Protein 3,NLR Family, Pyrin Domain Containing 3 Protein
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D014527	Uric Acid	An oxidation product, via XANTHINE OXIDASE, of oxypurines such as XANTHINE and HYPOXANTHINE. It is the final oxidation product of purine catabolism in humans and primates, whereas in most other mammals URATE OXIDASE further oxidizes it to ALLANTOIN.	2,6,8-Trihydroxypurine,Ammonium Acid Urate,Monosodium Urate,Monosodium Urate Monohydrate,Potassium Urate,Sodium Acid Urate,Sodium Acid Urate Monohydrate,Sodium Urate,Sodium Urate Monohydrate,Trioxopurine,Urate,Acid Urate, Ammonium,Acid Urate, Sodium,Acid, Uric,Monohydrate, Monosodium Urate,Monohydrate, Sodium Urate,Urate Monohydrate, Monosodium,Urate Monohydrate, Sodium,Urate, Ammonium Acid,Urate, Monosodium,Urate, Potassium,Urate, Sodium,Urate, Sodium Acid
D015210	Arthritis, Gouty	Arthritis, especially of the great toe, as a result of gout. Acute gouty arthritis often is precipitated by trauma, infection, surgery, etc. The initial attacks are usually monoarticular but later attacks are often polyarticular. Acute and chronic gouty arthritis are associated with accumulation of MONOSODIUM URATE in and around affected joints.	Gouty Arthritis,Arthritides, Gouty,Gouty Arthritides
D016207	Cytokines	Non-antibody proteins secreted by inflammatory leukocytes and some non-leukocytic cells, that act as intercellular mediators. They differ from classical hormones in that they are produced by a number of tissue or cell types rather than by specialized glands. They generally act locally in a paracrine or autocrine rather than endocrine manner.	Cytokine
D016328	NF-kappa B	Ubiquitous, inducible, nuclear transcriptional activator that binds to enhancer elements in many different cell types and is activated by pathogenic stimuli. The NF-kappa B complex is a heterodimer composed of two DNA-binding subunits: NF-kappa B1 and relA.	Immunoglobulin Enhancer-Binding Protein,NF-kappa B Complex,Nuclear Factor kappa B,Transcription Factor NF-kB,kappa B Enhancer Binding Protein,Ig-EBP-1,NF-kB,NF-kappaB,Nuclear Factor-Kappab,Complex, NF-kappa B,Enhancer-Binding Protein, Immunoglobulin,Factor NF-kB, Transcription,Factor-Kappab, Nuclear,Ig EBP 1,Immunoglobulin Enhancer Binding Protein,NF kB,NF kappa B Complex,NF kappaB,NF-kB, Transcription Factor,Nuclear Factor Kappab,Transcription Factor NF kB