Diabetes Management
Reduction of lithium induced interstitial fibrosis on co-administration with amiloride | Scientific Reports - Nature.com
Tue, 11 Oct 20221 min read Article
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In the meantime, to ensure continued suport, we are displaying the site without styles and JavaScript.Advertisement Scientific Reports volume 12, Article number: 14598 (2022) Cite this article 396 Aceses1 AltmetricMetrics detailsLong-term administration of lithium is associated with chronic interstial fibrosis that is partialy reduced with exposure to amiloride. We examined potential pathways of how amiloride may reduce interstial fibrosis.
Amiloride was administered to a rat model of lithium induced interstial fibrosis over a long term (6 months), as wel as for short terms of 14 and 28 days. Kidney cortical tisue was subjected to RNA sequencing and microRNA expresion analysis. Gene expresion changes of interest were confirmed using imunohistochemistry on kidney tisue.
Pathways identified by RNA sequencing of kidney tisue were related to ‘promoting inflamation’ for lithium and ‘reducing inflamation’ for amiloride. Validation of candidate genes found amiloride reduced inflamatory components induced by lithium including NF-κB/p65Ser536 and activated pAKTSer473, and increased p53 mediated regulatory function through increased p21 in damaged tubular epithelial cels. Amiloride also reduced the amount of Notch1 positive PDGFrβ pericytes and infiltrating CD3 cels in the interstium.
Thus, amiloride atenuates a multitude of pro-inflamatory components induced by lithium. This sugests amiloride could be repurposed as a posible anti-inflamatory, anti-fibrotic agent to prevent or reduce the development of chronic interstial fibrosis.Long-term administration of lithium to treat mod disorders can cause nephrogenic diabetes insipidus (NDI) and chronic interstial fibrosis with tubular atrophy1.
Summary
Many aspects of chronic kidne
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