Synthetic Fructoborate Administration: Effects on Cardiac Remodeling and Extracardiac Responses in Isoproterenol-Induced Cardiac Hypertrophy

Background: Synthetic fructoborate (sFB) is a boron-containing compound with reported biological effects, but its influence on cardiac remodeling remains poorly characterized. Objective: To evaluate the cardiac effects of short-term sFB administration and compare cardiac and extracardiac responses when sFB was administered before or after isoproterenol-induced cardiac hypertrophy. Methods: Male BALB/c mice received sFB (17, 34, or 68 mg/kg) for 3 days to assess cardiac morphology, p38 MAPK phosphorylation, Atrial Natriuretic Peptide (ANP) and Natriuretic Peptide B (BNP) mRNA expression, and oxidative stress-related markers. In a second experiment, cardiac hypertrophy was induced with isoproterenol (50 mg/kg, intraperitoneally, for 7 days), and sFB (34 mg/kg for 3 days) was administered before or after hypertrophy induction. Cardiac and extracardiac histological, molecular, and biochemical responses were evaluated. Results: Short-term sFB administration did not produce a consistent pattern of cardiac injury. The p-p38 MAPK/p38 MAPK ratio decreased, and 17 mg/kg sFB increased plasma glutathione (GSH) levels. When administered after hypertrophy induction, sFB reduced left ventricular wall thickness, cardiomyocyte area, and collagen I and III deposition and increased ventricular lumen area. Administration before isoproterenol exposure produced a different response, with some preserved structural parameters but persistent collagen deposition and increased expression of remodeling-associated genes. Extracardiac responses were heterogeneous and tissue-dependent, with notable hepatic alterations under some conditions. Conclusions: The effects of sFB on isoproterenol-induced cardiac hypertrophy depended on the timing of administration, with more consistent attenuation of structural remodeling when administered after hypertrophy induction. Further studies are required to establish its long-term safety, pharmacokinetics, and potential therapeutic relevance.