Ochratoxin A induces nephrotoxicity in vitro and in vivo via pyroptosis

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

doi:10.1007/s00204-021-02993-6

Cited by 40 publications

(29 citation statements)

References 55 publications

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“…After 24 h, we detected cell viability and LDH activity. Similar to what we've demonstrated before, [15] 1.0 to 4.0 μg/ml significant decrease in LDH activity at the concentrations of 2 μM (p < 0.05), 4, and 8 μM (p < 0.01) (Figure 1D). Therefore, we selected 2, 4 and 8 μM SeMet to conduct the subsequent experiment.…”

Section: Cytotoxicity Exploration Of Different Concentrations Of Ota and Semet On Mdck Cellssupporting

confidence: 90%

Selenomethionine alleviated Ochratoxin A induced pyroptosis and renal fibrotic factors expressions in MDCK cells

Liu

et al. 2021

J Biochem & Molecular Tox

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Ochratoxin A (OTA) is universally known to induce nephrotoxicity via inducing oxidative stress and apoptosis, inhibiting protein synthesis and activating autophagy.Our previous studies have proved that OTA induces nephrotoxicity in vitro and in vivo by adjusting the NOD-like receptor protein 3 (NLRP3) inflammasome activation and caspase-1-dependent pyroptosis. Based on these findings, we further investigated the protective role of selenomethionine (SeMet) on OTA-caused nephrotoxicity using the Madin-Darby canine kidney (MDCK) epithelial cells as an in vitro model, proposing to offer a new way for remedying OTA-induced nephrotoxicity by nutritional manipulation. We measured the cell vitality, lactate dehydrogenase (LDH) activity and the expression of renal fibrotic genes, NLRP3 inflammasome and pyroptosis related genes. MTT and LDH results indicated that SeMet supplementation significantly mitigated 2.0 μg/ml OTA-induced cytotoxicity in MDCK cells (p < 0.05). Meanwhile, SeMet alleviated OTA induced increase of reactive oxygen species in MDCK cells. Then, the expressions of α-SMA, Vimentin, and TGF-β were detected both in mRNA and protein levels. The results indicated 8 μM SeMet supplementation could significantly downregulate the expression of OTA-induced renal fibrosis-related genes (p < 0.05). In addition, the upregulation of OTA-induced NLRP3 inflammasome and pyroptosis downstream genes was also significantly inhibited by 8 μM of SeMet (p < 0.05). In summary, SeMet could alleviate OTA-induced renal fibrotic genes expression and reduce NLRP3-caspase-1dependent pyroptosis. Therefore, SeMet supplementation may become an effective approach for preserving animals from renal injury exposed to OTA.

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Section: Cytotoxicity Exploration Of Different Concentrations Of Ota and Semet On Mdck Cellssupporting

confidence: 90%

Selenomethionine alleviated Ochratoxin A induced pyroptosis and renal fibrotic factors expressions in MDCK cells

Liu

et al. 2021

J Biochem & Molecular Tox

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“…Also, OTA may promote an inflammatory status by modulating the expression of pro-inflammatory mediators (IL-6, TNFα) and pyroptosis-related genes (GSDMD, IL-1β, IL-18). These harmful effects were significantly abrogated by MCC950 pre-treatment, a specific NLRP3 inhibitor, and by caspase-1 knockdown (Li et al, 2021).…”

Section: Neurotoxicitymentioning

confidence: 98%

“…Indeed, OTA promoted the activation of NLRP3 inflammasome complex, which in turn activated caspase 1. This enzyme cleaved the precursors of inflammatory cytokines, IL-18 and IL-1β, by inducing the inflammatory response in neighboring cells (Li et al, 2021).…”

Section: Flow Cytometrymentioning

confidence: 99%

In vitro and in vivo evaluation of AFB1 and OTA-toxicity through immunofluorescence and flow cytometry techniques: A systematic review

Frangiamone

Cimbalo

Alonso-Garrido

et al. 2022

Food and Chemical Toxicology

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“…Besides apoptosis, OTA induced nephrotoxicity via activating NOD-like receptor protein 3 (NLRP3) inflammasome, and caspase1-dependent pyroptosis lead to renal fibrosis by evidence of increasing TGF-β and α-SMA during in vivo and in vitro study. This study offers a novel opinion or strategy for the treatment of OTA-induced renal fibrosis [ 46 ].…”

Section: The Mechanisms Underlying Ota Nephrotoxicitymentioning

confidence: 99%

Ochratoxin A-Induced Nephrotoxicity: Up-to-Date Evidence

Khoi

Chen

Lin

et al. 2021

IJMS

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Ochratoxin A (OTA) is a mycotoxin widely found in various foods and feeds that have a deleterious effect on humans and animals. It has been shown that OTA causes multiorgan toxicity, and the kidney is the main target of OTA among them. This present article aims to review recent and latest intracellular molecular interactions and signaling pathways of OTA-induced nephrotoxicity. Pyroptosis, lipotoxicity, organic anionic membrane transporter, autophagy, the ubiquitin-proteasome system, and histone acetyltransferase have been involved in the renal toxicity caused by OTA. Meanwhile, the literature reviewed the alternative or method against OTA toxicity by reducing ROS production, oxidative stress, activating the Nrf2 pathway, through using nanoparticles, a natural flavonoid, and metal supplement. The present review discloses the molecular mechanism of OTA-induced nephrotoxicity, providing opinions and strategies against OTA toxicity.

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Ochratoxin A induces nephrotoxicity in vitro and in vivo via pyroptosis

Cited by 40 publications

References 55 publications

Selenomethionine alleviated Ochratoxin A induced pyroptosis and renal fibrotic factors expressions in MDCK cells

Selenomethionine alleviated Ochratoxin A induced pyroptosis and renal fibrotic factors expressions in MDCK cells

In vitro and in vivo evaluation of AFB1 and OTA-toxicity through immunofluorescence and flow cytometry techniques: A systematic review

Ochratoxin A-Induced Nephrotoxicity: Up-to-Date Evidence

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