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Inflammation Research
Published in: Inflammation Research 6/2019

01-06-2019 | Kidney Injury | Original Research Paper

Chicoric acid prevents methotrexate-induced kidney injury by suppressing NF-κB/NLRP3 inflammasome activation and up-regulating Nrf2/ARE/HO-1 signaling

Authors: Sanaa M. Abd El-Twab, Omnia E. Hussein, Walaa G. Hozayen, May Bin-Jumah, Ayman M. Mahmoud

Published in: Inflammation Research | Issue 6/2019

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Abstract

Objective

Chicoric acid (CA) is a natural product with promising antioxidant and anti-inflammatory properties; however, its protective effect on methotrexate (MTX)-induced acute kidney injury (AKI) hasn’t been reported. We investigated the effect of CA on MTX-induced AKI in rats, pointing to the role of NF-κB/NLRP3 inflammasome and Nrf2/ARE/HO-1 signaling.

Materials and methods

Wistar rats received 25 mg/kg and 50 mg/kg CA for 15 days and a single injection of MTX at day 16. At day 19, the rats were killed, and samples were collected for analyses.

Results

MTX induced a significant increase in serum creatinine and urea, and kidney Kim-1, reactive oxygen species (ROS), malondialdehyde and nitric oxide levels. In addition, MTX-induced rats exhibited multiple histopathological alterations, diminished antioxidant defenses, and decreased expression of Nrf2, NQO-1 and HO-1. CA prevented histological alterations, ameliorated kidney function markers, attenuated ROS production and lipid peroxidation, and boosted antioxidant defenses. CA suppressed the expression of NF-κB p65, NLRP3, caspase-1 and IL-1β in the kidney of MTX-induced rats. Furthermore, CA inhibited MTX-induced apoptosis as evidenced by the decreased expression of BAX and caspase-3, and increased Bcl-2 gene expression.

Conclusions

CA prevented MTX-induced AKI through activation of Nrf2/ARE/HO-1 signaling, and attenuation of ROS-induced activation of NF-κB/NLRP3 inflammasome signaling.
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Metadata
Title
Chicoric acid prevents methotrexate-induced kidney injury by suppressing NF-κB/NLRP3 inflammasome activation and up-regulating Nrf2/ARE/HO-1 signaling
Authors
Sanaa M. Abd El-Twab
Omnia E. Hussein
Walaa G. Hozayen
May Bin-Jumah
Ayman M. Mahmoud
Publication date
01-06-2019
Publisher
Springer International Publishing
Published in
Inflammation Research / Issue 6/2019
Print ISSN: 1023-3830
Electronic ISSN: 1420-908X
DOI
https://doi.org/10.1007/s00011-019-01241-z

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