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

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, ß-MHC, TNF-α, IL-1ß, 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.

Indole-3 acetic acid induced cardiac hypertrophy in Wistar albino rats.

Indole-3-acetic acid (IAA) is the most widely utilized plant growth regulator. Despite its extensive usage, IAA is often overlooked as an environmental pollutant. Due to its protein-binding nature, it also functions as a uremic toxin, contributing to its association with chronic kidney disease (CKD). While in vitro and epidemiological research have demonstrated this association, the precise impact of IAA on cardiovascular disease in animal models is unknown. The main objective of this study is to conduct a mechanistic analysis of the cardiotoxic effects caused by IAA using male Wistar albino rats as the experimental model. Three different concentrations of IAA (125, 250, 500 mg/kg) were administered for 28 days. The circulating IAA concentration mimicked previously observed levels in CKD patients. The administration of IAA led to a notable augmentation in heart size and heart-to-body weight ratio, indicating cardiac hypertrophy. Echocardiographic assessments supported these observations, revealing myocardial thickening. Biochemical and gene expression analyses further corroborated the cardiotoxic effects of IAA. Dyslipidemia, increased serum c-Troponin-I levels, decreased SOD and CAT levels, and elevated lipid peroxidation in cardiac tissue were identified. Moreover, increased expression of cardiac inflammatory biomarkers, including ANP, BNP, ß-MHC, Col-III, TNF-α, and NF-κB, was also found in the IAA-treated animals. Histopathological analysis confirmed the cardiotoxic nature of IAA, providing additional evidence of its adverse effects on cardiovascular health. These results offer insights into the potential negative impact of IAA on cardiovascular function, and elucidating the underlying mechanisms of its cardiotoxicity.

Expanding germ-organ theory: Understanding non-communicable diseases through enterobacterial translocation.

Diverse microbial communities colonize different habitats of the human body, including gut, oral cavity, nasal cavity and tissues. These microbial communities are known as human microbiome, plays a vital role in maintaining the health. However, changes in the composition and functions of human microbiome can result in chronic low-grade inflammation, which can damage the epithelial cells and allows pathogens and their toxic metabolites to translocate into other organs such as the liver, heart, and kidneys, causing metabolic inflammation. This dysbiosis of human microbiome has been directly linked to the onset of several non-communicable diseases. Recent metabolomics studies have revealed that pathogens produce several uraemic toxins. These metabolites can serve as inter-kingdom signals, entering the circulatory system and altering host metabolism, thereby aggravating a variety of diseases. Interestingly, Enterobacteriaceae, a critical member of Proteobacteria, has been commonly associated with several non-communicable diseases, and the abundance of this family has been positively correlated with uraemic toxin production. Hence, this review provides a comprehensive overview of Enterobacterial translocation and their metabolites role in non-communicable diseases. This understanding may lead to the identification of novel biomarkers for each metabolic disease as well as the development of novel therapeutic drugs.