The possible effects of folic acid and postbiotic yeast on doxorubicin-induced cardiotoxicity in rats: interactions among the gut microbiota, antioxidants, and NLrp3 activities.

Doxorubicin (DOX) cardiotoxicity is a common adverse effect and is dose dependent. Folic acid (FA) and E-yeast (a deactivated form of Saccharomyces cerevisiae combined with wheat germ oil) are natural dietary supplements that may help mitigate these adverse effects. To compare the cardioprotective, antioxidant, anti-inflammatory, histological, and gut microbiota-modulating effects of FA and E-yeast on DOX-induced cardiac toxicity in rats. Twenty-four rats were divided into four groups: control, DOX-treated, FA + DOX, and E-yeast + DOX. The cardiac biomarkers lactate dehydrogenase and creatine kinase-MB (LDH, CK-MB), oxidative stress markers (malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GPX), inflammatory mediators (IL-6, TNF-α, IFN-γ, NLrp3), and fecal short-chain fatty acids (SCFAs) (acetic, butanoic, and propionic acids) were measured. In addition, left ventricular echocardiography and cardiac and colonic histology, including cardiac NADPH oxidase 4 (NOX4) expression, were assessed. DOX induced cardiac dysfunction, as shown by increased cardiac enzymes, left ventricular end-systolic diameter (LVESD), and left ventricular end-diastolic diameter (LVEDD) and decreased ejection fraction and SCFAs. Additionally, it increased the levels of MDA, IL-6, TNF-α, IFN-γ, and NLrp3. Folic acid restored cardiac, echocardiographic, oxidative, and inflammatory parameters to normal levels, whereas E-yeast only partially improved these parameters. SCFAs were restored to normal by both treatments. Histologically, DOX caused cardiomyocyte degeneration, necrosis, and increased NOX4 expression, resulting in degenerative disruption of the colonic mucosa. Folic acid was more effective at preserving the myocardial architecture and NOX4 expression, whereas E-yeast was more effective at minimizing colonic degenerative lesions. Folic acid demonstrated a more pronounced healing effect than did E-yeast on DOX-induced cardiac alterations.