Pyroptosis inhibition alleviates potassium oxonate- and monosodium urate-induced gouty arthritis in mice. 2022

Jing Tian, and Baichuan Wang, and Bin Xie, and Xinwei Liu, and Dapeng Zhou, and Xuening Hou, and Liangbi Xiang
Department of Orthopaedics, General Hospital of Northern Theater Command, Shenyang, China.

OBJECTIVE Pyroptosis has been found implicated in several diseases, however, whether it was involved in gouty arthritis remained unclear. Our study was performed to uncover the role of pyroptosis in gouty arthritis based on a mice model. METHODS Mouse gouty arthritis model was established by injections of potassium oxonate (PO), monosodium urate (MSU) and pyroptosis suppressor disulfiram. The diameter of the ankle joints was measured, and ankle joints morphology was observed with hematoxylin-eosin (H&E) staining. Uric acid, creatinine and blood urea nitrogen (BUN) concentrations were measured, while cytokines level and xanthine oxidase (XOD) activity were quantified. Relative pyroptosis markers expressions were determined using quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot as needed. RESULTS In mouse model, PO and MSU injections cause damage to right ankle, increase the root thickness ratio and uric acid, creatinine and BUN levels in serum and decrease the uric acid and creatinine levels in urine. Also, under PO and MSU treatment, up-regulated XOD activity, inflammatory cytokines levels and pyroptosis markers expressions are observed. Negative regulation of mice injury by disulfiram treatment is also observed. CONCLUSIONS Pyroptosis inhibition might alleviate PO- and MSU-induced gouty arthritis, providing possible therapeutic strategies for gouty arthritis.

UI MeSH Term Description Entries
D010094 Oxonic Acid Antagonist of urate oxidase. Oteracil
D003404 Creatinine Creatinine Sulfate Salt,Krebiozen,Salt, Creatinine Sulfate,Sulfate Salt, Creatinine
D004195 Disease Models, Animal Naturally-occurring or experimentally-induced animal diseases with pathological processes analogous to human diseases. Animal Disease Model,Animal Disease Models,Disease Model, Animal
D004221 Disulfiram A carbamate derivative used as an alcohol deterrent. It is a relatively nontoxic substance when administered alone, but markedly alters the intermediary metabolism of alcohol. When alcohol is ingested after administration of disulfiram, blood acetaldehyde concentrations are increased, followed by flushing, systemic vasodilation, respiratory difficulties, nausea, hypotension, and other symptoms (acetaldehyde syndrome). It acts by inhibiting aldehyde dehydrogenase. Tetraethylthiuram Disulfide,Alcophobin,Antabus,Antabuse,Anticol,Bis(diethylthiocarbamoyl) Disulfide,Dicupral,Esperal,Tetraethylthioperoxydicarbonic Diamide, ((H2N)C(S))2S2,Teturam,Disulfide, Tetraethylthiuram
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000069292 Pyroptosis Type of programmed cell death associated with infection by intracellular pathogens. It is characterized by INFLAMMASOME formation; activation of CASPASE 1; and CYTOKINES mediated inflammation. Caspase-1 Dependent Cell Death,Inflammatory Apoptosis,Pyroptotic Cell Death,Apoptoses, Inflammatory,Apoptosis, Inflammatory,Caspase 1 Dependent Cell Death,Cell Death, Pyroptotic,Cell Deaths, Pyroptotic,Death, Pyroptotic Cell,Deaths, Pyroptotic Cell,Inflammatory Apoptoses,Pyroptoses,Pyroptotic Cell Deaths
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

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