Combined Docosahexaenoic Acid and Captopril Treatment Attenuates Indole Acetic Acid Induced Cardiovascular Injury in Chronic Kidney Disease.

Chronic kidney disease (CKD) is associated with the accumulation of protein-bound uremic toxins (PBUTs), which cause cardiovascular dysfunction via oxidative stress, inflammation, and fibrosis. Indole-3-acetic acid (IAA), a uremic toxin generated from the gut microbiota, has been identified as a key modulator of cardiovascular injury in CKD. This study looked at the therapeutic efficacy of a 10% docosahexaenoic acid (DHA) supplemented diet paired with captopril (100 mg/kg) in CKD rats exposed to IAA (50 mg/kg) for 30 days. DHA alone enhanced IAA clearance and lowered systemic levels, while the DHA + captopril combination offered the most cardio-protection. Serum troponin-I, CK-MB, and lactate dehydrogenase (LDH) levels were significantly reduced, while antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT) were protected. Gene expression analysis revealed lower levels of heart hypertrophic (ANP, BNP, β-MHC) and fibrotic (Col-I, Col-III) markers, which align with the histological findings of reduced myocardial fibrosis and structural preservation. The co-treatment reduced inflammation by inhibiting the AhR-NF-κB signaling pathway and TNF-α expression. These findings demonstrate that DHA in combination with captopril mitigates IAA-induced cardiovascular damage in CKD and represents a promising adjunct strategy to reduce cardiovascular complications in uremic condition.