Erythritol can promote cardiac injury in C57 mice under heat stress

During the past decade, heat waves have increased in both frequency and intensity and are now recognised as a global public-health emergency. Erythritol, a sugar alcohol that is abundant in the human diet and the environment, may exacerbate heat-related cardiac injury, yet this possibility has not been examined. The present study combines network toxicology, controlled in vivo exposure, transcriptomic profiling and molecular docking to clarify how erythritol modulates heat-induced myocardial damage. A network toxicology screen indicated that erythritol can potentiate heat stress injury through the TNF signaling pathway and the apoptosis regulators BCL2 and CASP3. We next exposed specific-pathogen-free male C57BL/6 mice to an elevated ambient temperature for 28 consecutive days. Erythritol was administered daily at human-relevant doses calculated by body surface area: low, mediumand high. All treatments reduced the heart-to-body-weight ratio under heat stress. High and medium doses further elevated myocardial levels of pro-inflammatory cytokinesand oxidative stress markers ), concomitant with increased serum activities of cardiac injury enzymes . Transcriptomic analysis revealed marked down-regulation of the cardioprotective heat-shock genes Hspa1a and Hspa1b. Molecular docking predicted stable binding of erythritol to both HSP72 and HSP70 , and Western blotting confirmed reduced HSP70 protein expression and augmented cardiomyocyte apoptosis. In conclusion, these results demonstrate that erythritol, at human-equivalent exposures, aggravates heat-induced cardiac injury in mice and highlight the importance of revisiting current intake recommendations during periods of extreme heat in human.