PhD Scientific Days 2026

Poster Session 2.Q - Cardiovascular Medicine and Research

Sex Differences of Febuxostat Treatment in Cardiovascular Diseases: Echocardiographic Evaluation of an Isoprenaline-Induced Myocardial Injury Model

Name of the presenter

Tóth, Artúr

Institute/workplace of the presenter

Department of Pharmacology and Pharmacotherapy, Semmelweis University

Authors

dr. Artúr Tóth^1,2, dr. Sára Jezsoviczky^1,2, Andrea Kovács^1,2, Zsombor Hegedüs^1,2, dr. Márk Jakab^1,2, Dr. Zoltán V. Varga^1,2,3, Prof. Dr. Péter Ferdinandy^1,2,4, Dr. Zsófia Onódi^1,2
1: Department of Pharmacology and Pharmacotherapy, Semmelweis University
2: Center for Pharmacology and Drug Research & Development, Semmelweis University
3: HUN-REN-SU System Pharmacology Research Group, Department of Pharmacology and Pharmacotherapy, Semmelweis University
4: Pharmahungary Group, H-6722 Szeged

Text of the abstract

Introduction: Recently, the CARES trial has revealed elevated mortality in patients with febuxostat treatment in comparison with allopurinol, two xanthine oxidase inhibitors used in hyperuricemia, meanwhile other trials have shown no alteration in survival. Additionally, females with gout are more vulnerable to cardiovascular diseases. Therefore, anti-gout medications might have different effects in males and females. However, sex differences of febuxostat effects are less known.
Aims: Our objective was to evaluate the echocardiographic and fibrotic differences of febuxostat and allopurinol in a myocardial injury mouse model in both sexes.
Methods: C57BL/6 mice of both sexes were used in present study. Animals were randomized into five groups: vehicle control, isoprenaline (ISOP) only, febuxostat only, febuxostat plus with ISOP, and allopurinol plus ISOP. Mice received daily oral treatment with febuxostat (10 mg/kg body weight) or allopurinol (20 mg/kg) for 5 weeks. On the 14th day, myocardial injury was induced with a single dose of ISOP (200 mg/kg) injection and maintained with reduced dose (100 mg/kg) twice weekly for the rest of the study. Echocardiography was obtained 4 times: baseline measurements, before and after the induction and before the termination. Fibrosis was analyzed with picrosirius red staining.
Results: Diminished relative wall thickness (RWT) was observed in febuxostat plus ISOP treatment group (RWT=0.493±0.053), in comparison with ISOP-only group (RWT=0.662±0.026) in females. Febuxostat also resulted in higher end-systolic and end-diastolic values. Additionally, significant decline in fractional shortening was observed in febuxostat plus ISOP group (FS before/after induction: 27.244±3.666/19.512±5.047), meanwhile such alteration was not present in the allopurinol plus ISOP group. On the other hand, males with febuxostat plus ISOP were presented with enhanced wall thickening (RWT=0.557±0.119) in comparison with febuxostat-only group (RWT=0.403±0.059). There was no significant alteration in fibrosis.
Conclusion: Our study revealed that febuxostat in females diminishes wall thickening, meanwhile in males it contributes to more pronounced wall thickness. In future studies, mechanistic insights of febuxostat on females will be investigated.
Funding: NKFIH 152247 to Z.O.; NKL RRF‐2.3.1‐21‐2022‐00003; SE250-2025-311 to A.T.