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

Abstract

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.