The protective effect of 3‐indolepropanoic acid on aflatoxin B1‐induced systemic perturbation of the liver and kidney function in rats

• Published in: Fundamental & clinical pharmacology Vol. 37; no. 2; pp. 369 - 384
• Main Authors: Owumi, Solomon E., Arunsi, Uche O., Oyelere, Adegboyega K.
• Format: Journal Article
• Language: English
• Published: England Wiley Subscription Services, Inc 01.04.2023
• Subjects: 3‐indole propanoic acid; Aflatoxin B1; Aflatoxin B1 - metabolism; Aflatoxin B1 - toxicity; Aflatoxins; Animals; antioxidant; Apoptosis; Biomarkers; Biomarkers - metabolism; Damage; DNA adducts; DNA Adducts - metabolism; DNA Adducts - pharmacology; DNA damage; DNA damage and apoptosis; Glutathione - metabolism; hepatorenal toxicity; Immunoassays; Inflammation; Inflammation - metabolism; Injury prevention; Interleukin 10; Intestinal microflora; Kidney - metabolism; Lipid peroxidation; Lipids; Liver; Male; Metabolism; Metabolites; Oral administration; Oxidative Stress; oxido‐inflammatory response; Peroxidation; Perturbation; Pharmacology; Propionic acid; Rats; Reactive oxygen species; Renal function; Toxicity; Tryptophan; Tryptophan - metabolism; Tryptophan - pharmacology; Xenobiotics; antioxidant; aflatoxin B1; hepatorenal toxicity; oxido-inflammatory response; 3-indole propanoic acid; DNA damage and apoptosis
• ISSN: 0767-3981; 1472-8206
• DOI: 10.1111/fcp.12842

Aflatoxin B1 (AFB1) is known to derange the hepatorenal system by redox, DNA adduct formation and apoptotic networks. Endogenous 3‐indole propionic acid (3‐IPA) is a metabolite of tryptophan metabolism by gut microbiota that can protect against redox imbalance, inflammation and cellular lipid damage. We investigated the beneficial effect of 3‐IPA against AFB1‐mediated organ toxicity in male rats post 28 days of consecutive treatment. The 3‐IPA (25 and 50 mg/kg) was orally administered alongside AFB1 (50 μg/kg) treatment. Biochemical and enzyme‐linked immunosorbent assays were utilised to examine biomarkers of hepatorenal function, oxidative status and inflammation. DNA damage and apoptosis were also assessed, and histological staining techniques were used to investigate hepatorenal tissues for pathological indicators. The 3‐IPA supplementation abated AFB1‐mediated increases in biomarkers of hepatic and renal dysfunction in rat serum. Co‐administration of 3‐IPA further reduced AFB1‐induced redox imbalance (by upregulating antioxidant mediators and enzymes [GSH, TSH, Trx, Trx‐R, SOD, CAT, GPx and GST]; reducing reactive oxygen species, lipid peroxidation and DNA adduct [RONS, LPO and 8‐OH‐dG] formation; suppressing pro‐inflammatory and apoptotic mediators [XO, MPO, NO, IL‐1β and Casp −9 and −3]; and upregulating the level of interleukin 10 (IL‐10). Moreover, treatment with 3‐IPA lessened hepatorenal tissue injuries. These findings suggest that augmenting 3‐IPA endogenously from tryptophan metabolism may provide a novel strategy to forestall xenobiotics‐mediated hepatorenal toxicity, including AFB1.