Article ; Online: Discovery of 2,8-dihydroxyadenine in HUA patients with uroliths and biomarkers for its associated nephropathy.
Biochimica et biophysica acta. Molecular basis of disease
2024 Volume 1870, Issue 4, Page(s) 167051
Abstract: ... Hence, we hypothesized that uroliths from hyperuricemia (HUA) patients, which is closely associated with gout ... may contain 2,8-DHA. In this study, 2,8-DHA in uroliths and serum of HUA patients were determined using HPLC ... in the majority of these HUA patients. Additionally, the differentially expressed genes between 2,8-DHA ...
| Abstract | Currently, it is acknowledged that gout is caused by uric acid (UA). However, some studies have revealed no correlation between gout and UA levels, and growing evidence suggests that 2,8-dihydroxyadenine (2,8-DHA), whose structural formula is similar to UA but is less soluble, may induce gout. Hence, we hypothesized that uroliths from hyperuricemia (HUA) patients, which is closely associated with gout, may contain 2,8-DHA. In this study, 2,8-DHA in uroliths and serum of HUA patients were determined using HPLC. Moreover, bioinformatics was used to investigate the pathogenic mechanisms of 2,8-DHA nephropathy. Subsequently, a mouse model of 2,8-DHA nephropathy established by the gavage administration of adenine, as well as a model of injured HK-2 cells induced by 2,8-DHA were used to explore the pathogenesis of 2,8-DHA nephropathy. Interestingly, 2,8-DHA could readily deposit in the cortex of the renal tubules, and was found in the majority of these HUA patients. Additionally, the differentially expressed genes between 2,8-DHA nephropathy mice and control mice were found to be involved in inflammatory reactions. Importantly, CCL2 and IL-1β genes had the maximum degree, closeness, and betweenness centrality scores. The expressions of CCL2 and IL-1β genes were significantly increased in the serum of 24 HUA patients with uroliths, indicating that they may be significant factors for 2,8-DHA nephropathy. Further analysis illustrated that oxidative damage and inflammation were the crucial processes of 2,8-DHA renal injury, and CCL2 and IL-1β genes were verified to be essential biomarkers for 2,8-DHA nephropathy. These findings revealed further insights into 2,8-DHA nephropathy, and provided new ideas for its diagnosis and treatment. |
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| MeSH term(s) | Humans ; Mice ; Animals ; Hyperuricemia/metabolism ; Kidney Diseases ; Kidney/metabolism ; Gout ; Uric Acid/metabolism ; Adenine/analogs & derivatives |
| Chemical Substances | 2,8-dihydroxyadenine (30377-37-8) ; Uric Acid (268B43MJ25) ; Adenine (JAC85A2161) |
| Language | English |
| Publishing date | 2024-02-07 |
| Publishing country | Netherlands |
| Document type | Journal Article |
| ZDB-ID | 60-7 |
| ISSN | 1879-260X ; 1879-2596 ; 1872-8006 ; 1879-2642 ; 1879-2618 ; 1879-2650 ; 0006-3002 ; 0005-2728 ; 0005-2736 ; 0304-4165 ; 0167-4838 ; 1388-1981 ; 0167-4889 ; 0167-4781 ; 0304-419X ; 1570-9639 ; 0925-4439 ; 1874-9399 |
| ISSN (online) | 1879-260X ; 1879-2596 ; 1872-8006 ; 1879-2642 ; 1879-2618 ; 1879-2650 |
| ISSN | 0006-3002 ; 0005-2728 ; 0005-2736 ; 0304-4165 ; 0167-4838 ; 1388-1981 ; 0167-4889 ; 0167-4781 ; 0304-419X ; 1570-9639 ; 0925-4439 ; 1874-9399 |
| DOI | 10.1016/j.bbadis.2024.167051 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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