Indole-3-acetic acid exposure leads to cardiovascular inflammation and fibrosis in chronic kidney disease rat model

• Published in: Food and chemical toxicology Vol. 192; p. 114917
• Main Authors: Nayak, S.P. Ramya Ranjan, Boopathi, Seenivasan, Chandrasekar, Munisamy, Panda, Siva Prasad, Manikandan, K., Chitra, Vellapandian, Almutairi, Bader O., Arokiyaraj, Selvaraj, Guru, Ajay, Arockiaraj, Jesu
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01-10-2024
• Subjects: Animals; Cardiotoxicity; Cardiovascular Diseases; Chronic kidney disease; Disease Models, Animal; Echocardiogram; Fibrosis; Indole-3-acetic acid; Indoleacetic Acids - pharmacology; Inflammation - chemically induced; Male; Myocardium - metabolism; Myocardium - pathology; Oxidative Stress - drug effects; Rats; Rats, Sprague-Dawley; Renal Insufficiency, Chronic - chemically induced; Renal Insufficiency, Chronic - metabolism; Uremic toxin; Echocardiogram; Chronic kidney disease; Cardiotoxicity; Indole-3-acetic acid; Uremic toxin
• ISSN: 0278-6915; 1873-6351; 1873-6351
• DOI: 10.1016/j.fct.2024.114917

Indole-3-acetic acid (IAA), a protein-bound uremic toxin, has been linked to cardiovascular morbidity and mortality in chronic kidney disease (CKD) patients. This study explores the influence of IAA (125 mg/kg) on cardiovascular changes in adenine sulfate-induced CKD rats. HPLC analysis revealed that IAA-exposed CKD rats had lower excretion and increased circulation of IAA compared to both CKD and IAA control groups. Moreover, echocardiography indicated that CKD rats exposed to IAA exhibited heart enlargement, thickening of the myocardium, and cardiac hypertrophy in contrast to CKD or IAA control group. Biochemical analyses supported the finding that IAA-induced CKD rats had elevated serum levels of c-Tn-I, CK-MB, and LDH; there was also evidence of oxidative stress in cardiac tissues, with a significant decrease in SOD and CAT levels, as well as an increase in MDA levels. The gene expression analysis found significant increases in ANP, BNP, β-MHC, TNF-α, IL-1β, and NF-κB levels in IAA-exposed CKD groups in contrast to the CKD or IAA control group. In addition, higher cardiac fibrosis markers, including Col-I and Col-III. The findings of this study indicate that IAA could trigger cardiovascular inflammation and fibrosis in CKD conditions.
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