Tags

Type your tag names separated by a space and hit enter

Ferulic acid protects against methotrexate nephrotoxicity via activation of Nrf2/ARE/HO-1 signaling and PPARγ, and suppression of NF-κB/NLRP3 inflammasome axis.
Food Funct. 2019 Aug 01; 10(8):4593-4607.FF

Abstract

Drug-induced nephrotoxicity contributes to acute kidney injury (AKI) and represents a major problem in the clinical setting. We investigated the possible involvement of NLRP3 inflammasome activation in methotrexate (MTX)-induced nephrotoxicity and the protective potential of ferulic acid (FA), pointing out the role of PPARγ and Nrf2/HO-1 signaling. Rats that received MTX showed a significant increase in circulating creatinine and urea, and kidney Kim-1 levels along with multiple histological alterations. Reactive oxygen species (ROS), malondialdehyde and nitric oxide levels showed a significant increase in the kidney of rats that received MTX, while antioxidant defenses were diminished. FA ameliorated kidney function markers, prevented histological alterations, suppressed ROS production and enhanced antioxidant defenses. FA inhibited MTX-induced inflammasome activation as showed by the decreased phosphorylation of NF-κB, and expression of NLRP3, caspase-1 and IL-1β. MTX caused apoptosis marked by increased expression of BAX, cytochrome c and caspase-3, and suppressed Bcl-2, effects that were significantly reversed in FA-treated groups. In addition, FA up-regulated Nrf2/ARE/HO-1 signaling and PPARγ expression in the kidney of MTX-induced rats. In conclusion, activation of NLRP3 inflammasome may represent a new mechanism for MTX nephrotoxicity. FA up-regulated PPARγ and Nrf2 signaling, prevented overproduction of ROS, and suppressed NF-κB/NLRP3 inflammasome axis and apoptosis in the kidney of MTX-induced rats.

Authors+Show Affiliations

Physiology Division, Department of Zoology, Faculty of Science, Beni-Suef University, Egypt. ayman.mahmoud@science.bsu.edu.eg.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31289794

Citation

Mahmoud, Ayman M., et al. "Ferulic Acid Protects Against Methotrexate Nephrotoxicity Via Activation of Nrf2/ARE/HO-1 Signaling and PPARγ, and Suppression of NF-κB/NLRP3 Inflammasome Axis." Food & Function, vol. 10, no. 8, 2019, pp. 4593-4607.
Mahmoud AM, Hussein OE, Abd El-Twab SM, et al. Ferulic acid protects against methotrexate nephrotoxicity via activation of Nrf2/ARE/HO-1 signaling and PPARγ, and suppression of NF-κB/NLRP3 inflammasome axis. Food Funct. 2019;10(8):4593-4607.
Mahmoud, A. M., Hussein, O. E., Abd El-Twab, S. M., & Hozayen, W. G. (2019). Ferulic acid protects against methotrexate nephrotoxicity via activation of Nrf2/ARE/HO-1 signaling and PPARγ, and suppression of NF-κB/NLRP3 inflammasome axis. Food & Function, 10(8), 4593-4607. https://doi.org/10.1039/c9fo00114j
Mahmoud AM, et al. Ferulic Acid Protects Against Methotrexate Nephrotoxicity Via Activation of Nrf2/ARE/HO-1 Signaling and PPARγ, and Suppression of NF-κB/NLRP3 Inflammasome Axis. Food Funct. 2019 Aug 1;10(8):4593-4607. PubMed PMID: 31289794.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Ferulic acid protects against methotrexate nephrotoxicity via activation of Nrf2/ARE/HO-1 signaling and PPARγ, and suppression of NF-κB/NLRP3 inflammasome axis. AU - Mahmoud,Ayman M, AU - Hussein,Omnia E, AU - Abd El-Twab,Sanaa M, AU - Hozayen,Walaa G, Y1 - 2019/07/10/ PY - 2019/7/11/pubmed PY - 2020/2/6/medline PY - 2019/7/11/entrez SP - 4593 EP - 4607 JF - Food & function JO - Food Funct VL - 10 IS - 8 N2 - Drug-induced nephrotoxicity contributes to acute kidney injury (AKI) and represents a major problem in the clinical setting. We investigated the possible involvement of NLRP3 inflammasome activation in methotrexate (MTX)-induced nephrotoxicity and the protective potential of ferulic acid (FA), pointing out the role of PPARγ and Nrf2/HO-1 signaling. Rats that received MTX showed a significant increase in circulating creatinine and urea, and kidney Kim-1 levels along with multiple histological alterations. Reactive oxygen species (ROS), malondialdehyde and nitric oxide levels showed a significant increase in the kidney of rats that received MTX, while antioxidant defenses were diminished. FA ameliorated kidney function markers, prevented histological alterations, suppressed ROS production and enhanced antioxidant defenses. FA inhibited MTX-induced inflammasome activation as showed by the decreased phosphorylation of NF-κB, and expression of NLRP3, caspase-1 and IL-1β. MTX caused apoptosis marked by increased expression of BAX, cytochrome c and caspase-3, and suppressed Bcl-2, effects that were significantly reversed in FA-treated groups. In addition, FA up-regulated Nrf2/ARE/HO-1 signaling and PPARγ expression in the kidney of MTX-induced rats. In conclusion, activation of NLRP3 inflammasome may represent a new mechanism for MTX nephrotoxicity. FA up-regulated PPARγ and Nrf2 signaling, prevented overproduction of ROS, and suppressed NF-κB/NLRP3 inflammasome axis and apoptosis in the kidney of MTX-induced rats. SN - 2042-650X UR - https://www.unboundmedicine.com/medline/citation/31289794/Ferulic_acid_protects_against_methotrexate_nephrotoxicity_via_activation_of_Nrf2/ARE/HO_1_signaling_and_PPARγ_and_suppression_of_NF_κB/NLRP3_inflammasome_axis_ L2 - https://doi.org/10.1039/c9fo00114j DB - PRIME DP - Unbound Medicine ER -