# Multi-omics analysis reveals that alginate oligosaccharides mitigate ochratoxin A-induced renal impairment in mice and is relevant to the regulation of PPAR signaling

## TL;DR

This study shows that alginate oligosaccharides protect mice from kidney damage caused by ochratoxin A by activating the PPAR signaling pathway.

## Contribution

The study identifies a novel metabolic-transcriptional network involving PPAR signaling through which marine-derived AOS mitigates OTA-induced nephrotoxicity.

## Key findings

- AOS treatment alleviated OTA-induced renal injury in mice, including glomerular and mitochondrial damage.
- Multi-omics analysis showed AOS activates PPAR signaling and upregulates key genes like Aldh1a3, Cps1, and Cox8b.
- Protective metabolites like L-arginine and carnosine accumulated through coordinated regulation of amino acid metabolism and mTOR signaling.

## Abstract

Ochratoxin A (OTA) is a core environmental toxin that induces kidney injury by interfering with glomerular filtration, antioxidant defense, and tubular transport functions. Alginate oligosaccharides (AOS), as active substances from marine, carry natural antioxidant, anti-inflammatory 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.

OTA induced renal injury in mice, manifested by glomerular capsule blurring, lymphocytic infiltration, and mitochondrial damage in tubular epithelial cells. Treatment with AOS significantly alleviated these pathological changes. Multi‑omics analysis revealed that AOS activated the PPAR signaling pathway, upregulating key genes (Aldehyde Dehydrogenase 1 Family Member A3 (Aldh1a3), Carbamoyl-phosphate synthase 1 (Cps1), Cytochrome c oxidase subunit 8B (Cox8b)), which drove the accumulation of protective metabolites such as L‑arginine and carnosine. This protective process involved coordinated regulation of amino acid metabolism, mTOR signaling, and PPAR pathways, illustrating a novel metabolic‑transcriptional network through which AOS mitigates OTA‑induced nephrotoxicity.

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.