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Archives of Toxicology
Erschienen in:

01.04.2021 | Biologics

Ochratoxin A induces nephrotoxicity in vitro and in vivo via pyroptosis

verfasst von: Hu Li, Xinru Mao, Kai Liu, Jiahao Sun, Benrui Li, Rahmani Mohammad Malyar, Dandan Liu, Cuiling Pan, Fang Gan, Yunhuan Liu, Kehe Huang, Xingxiang Chen

Erschienen in: Archives of Toxicology | Ausgabe 4/2021

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Abstract

Ochratoxin A (OTA), a prevalent nephrotoxic mycotoxin contaminant in food and feedstuff, has been reported to induce renal injury. To disclose the nephrotoxicity of continuous administration of OTA and to investigate potential mechanisms related to pyroptosis, male C57BL/6 mice were intraperitoneally injected with 1.0 and 2.0 mg/kg B.W. OTA every other day for 14 days. At 2.0 mg/kg B.W. OTA administration significantly increased histological injury and renal fibrosis molecules (α-SMA, Vimentin, TGF-β) and activated the NOD-like receptor protein 3 (NLRP3) inflammasome and induced pyroptosis compared with control. In the in vitro tests, Madin–Darby canine kidney (MDCK) epithelial cells were exposed to 0–4.0 μg/ml OTA for 24 h in serum-free medium. Data showed that OTA dose-dependently affected cell viability and significantly up-regulated renal fibrosis genes (α-SMA, Vimentin, TGF-β). 2.0 μg/ml OTA significantly induced NLRP3 inflammasome activation and caspase-1-dependent pyroptosis, increasing the expression and secretion of pro-inflammatory cytokines (IL-6, TNF-α) and pyroptosis-related genes (GSDMD, IL-1β, IL-18) in MDCK cells. These outcomes were significantly abrogated after inhibiting NLRP3 activation with inhibitor MCC950 and silencing NLRP3 with small interfering RNA (siRNA). Furthermore, knockdown of caspase-1 also ameliorated OTA-induced renal fibrosis via the inhibition of pyroptosis. Collectively, the chosen doses of OTA-triggered nephrotoxicity through NLRP3 inflammasome activation and caspase-1-dependent pyroptosis both in vitro and in vivo.
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Metadaten
Titel
Ochratoxin A induces nephrotoxicity in vitro and in vivo via pyroptosis
verfasst von
Hu Li
Xinru Mao
Kai Liu
Jiahao Sun
Benrui Li
Rahmani Mohammad Malyar
Dandan Liu
Cuiling Pan
Fang Gan
Yunhuan Liu
Kehe Huang
Xingxiang Chen
Publikationsdatum
01.04.2021
Verlag
Springer Berlin Heidelberg
Erschienen in
Archives of Toxicology / Ausgabe 4/2021
Print ISSN: 0340-5761
Elektronische ISSN: 1432-0738
DOI
https://doi.org/10.1007/s00204-021-02993-6

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