Uric Acid: A New Perspective for Exploring the Pathological Process of Anthracycline-Induced Cardiotoxicity

TL;DR

This study explores how elevated uric acid levels contribute to heart damage caused by anthracycline chemotherapy, suggesting that lowering uric acid could help prevent this toxicity.

Contribution

The study identifies uric acid as a potential contributor to anthracycline-induced cardiotoxicity and proposes UA-lowering strategies as a novel prevention approach.

Findings

Elevated uric acid levels were significantly associated with cardiac damage markers in human data.

Animal experiments showed that high uric acid worsens anthracycline-induced cardiotoxicity.

Uric acid clearance in animal models alleviated cardiotoxicity symptoms.

Abstract

Anthracycline’s clinical application is often hampered by severe life-threatening cardiotoxicity, which could result in death in approximately one-third of patients. Previous studies have found that during the anthracycline-induced cardiotoxicity (AIC), uric acid (UA) levels increase abnormally. However, the role of UA in AIC remains elusive. Here, we conducted a correlation analysis between UA and cardiac damage markers (NT-pro-BNP, hs-cTnT, LDH, CRP and hs-CRP) by using the National Health and Nutrition Examination Survey database (NHANES); the results revealed that the elevated UA levels showed significant positive associations with the levels of several cardiac damage markers. Secondly, molecular docking experiments suggested potential binding interactions between UA and BNP, cTnT, CRP, and LDH. Finally, animal experiments were performed to validate this correlation we explored and further validated the effect of UA on AIC by adding or lowering UA in animal models. We observed that under high uric acid (HUA) conditions, AIC not only manifested earlier but also progressed more severely. In contrast, AIC was alleviated under UA clearance conditions. Collectively, these results suggested that HUA might be an important contributing factor in the development and progression of AIC, supporting the further investigation of UA-lowering strategies for potential prevention. This work might offer new prevention and treatment strategies for AIC.

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