ORIGINAL RESEARCH article
Front. Vet. Sci.
Sec. Animal Nutrition and Metabolism
Multi-omics Analysis Reveals that Alginate Oligosaccharides Mitigate Ochratoxin A-induced Renal Impairment in Mice and is Relevant to the Regulation of PPAR Signaling
Provisionally accepted
- Guangdong Ocean University School of Coastal Agricultural Sciences, Zhanjiang, China
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Ochratoxin A (OTA) is a common environmental toxin that can cause kidney injury by disrupting glomerular filtration, antioxidant defense, and tubular transport functions. Alginate oligosaccharides (AOS), derived from marine sources, contain natural antioxidants, anti-inflammatory properties, and other biological activities. The purpose of this study is to explore the molecular network of AOS against nephrotoxicity caused by OTA. A total of 36 5-week male mice were randomly divided into three groups:the CON group, the OTA group (250 μg/kg B.W. OTA) and the AOS + OTA group (400 mg/kg B.W. AOS +250 μg/kg B.W. OTA). The treatment was continued for 21 d. The results showed that OTA results in blurred balloon lumen and renal cortical lymphocyte infiltration, accompanied by mild edema of tubular epithelial cells, blurred mitochondrial crest morphology, and a reduction in number and area of mitochondria. AOS treatment alleviates the aforementioned kidney damage caused by OTA. Metabolomics results suggested that AOS increased the content of Ascorbate, Carnosine and Thymidine, and reduced the accumulation of Pendimethalin in the kidney of mice exposed to OTA, and the KEGG pathway was mainly enriched in protein digestion and absorption, amino acid metabolism and mTOR signaling. Transcriptomics results showed that AOS up-regulated the gene expression of Aldehyde Dehydrogenase 1 Family Member A3 (Aldh1a3), Carbamoyl-phosphate synthase 1 (Cps1), Cytochrome c oxidase subunit 8B (Cox8b) and Haptoglobin (Hp) in the kidney of mice exposed to OTA, and the KEGG enrichment analysis was mainly enriched in the PPAR signaling pathway. Integrative multi-omics analysis indicated that AOS synchronously upregulated Cps1, Aldh1a3, and Cox8b through the PPAR pathway, driving the accumulation of protective metabolites such as L-Arginine and Carnosine. In summary, the results of this study reveal that AOS antagonizes OTA-induced nephrotoxicity in mice through PPAR signaling axis, thus providing new insight into the renal protection mechanism of marine active substances.
Keywords: Alginate oligosaccharides, multi-omics, nephrotoxicity, Ochratoxin A, PPARsignaling
Received: 10 Sep 2025; Accepted: 12 Dec 2025.
Copyright: © 2025 Ye, Zhao, Yao, Zhang, Li and Liu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Wen-Chao Liu
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