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Chicoric acid prevents methotrexate-induced kidney injury by suppressing NF-κB/NLRP3 inflammasome activation and up-regulating Nrf2/ARE/HO-1 signaling.
Inflamm Res. 2019 Jun; 68(6):511-523.IR

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.

Authors+Show Affiliations

Physiology Division, Department of Zoology, Faculty of Science, Beni-Suef University, Beni-Suef, Egypt.Physiology Division, Department of Zoology, Faculty of Science, Beni-Suef University, Beni-Suef, Egypt.Biochemistry Division, Chemistry Department, Faculty of Science, Beni-Suef University, Beni-Suef, Egypt. Biotechnology and Life Sciences Department, Faculty of Postgraduate Studies for Advanced Sciences (PSAS), Beni-Suef University, Beni-Suef, Egypt.Department of Biology, College of Science, Princess Nourah bint Abdulrahman University, Riyadh, Saudi Arabia.Physiology Division, Department of Zoology, Faculty of Science, Beni-Suef University, Beni-Suef, Egypt. ayman.mahmoud@science.bsu.edu.eg.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31037316

Citation

Abd El-Twab, Sanaa M., et al. "Chicoric Acid Prevents Methotrexate-induced Kidney Injury By Suppressing NF-κB/NLRP3 Inflammasome Activation and Up-regulating Nrf2/ARE/HO-1 Signaling." Inflammation Research : Official Journal of the European Histamine Research Society ... [et Al.], vol. 68, no. 6, 2019, pp. 511-523.
Abd El-Twab SM, Hussein OE, Hozayen WG, et al. Chicoric acid prevents methotrexate-induced kidney injury by suppressing NF-κB/NLRP3 inflammasome activation and up-regulating Nrf2/ARE/HO-1 signaling. Inflamm Res. 2019;68(6):511-523.
Abd El-Twab, S. M., Hussein, O. E., Hozayen, W. G., Bin-Jumah, M., & Mahmoud, A. M. (2019). Chicoric acid prevents methotrexate-induced kidney injury by suppressing NF-κB/NLRP3 inflammasome activation and up-regulating Nrf2/ARE/HO-1 signaling. Inflammation Research : Official Journal of the European Histamine Research Society ... [et Al.], 68(6), 511-523. https://doi.org/10.1007/s00011-019-01241-z
Abd El-Twab SM, et al. Chicoric Acid Prevents Methotrexate-induced Kidney Injury By Suppressing NF-κB/NLRP3 Inflammasome Activation and Up-regulating Nrf2/ARE/HO-1 Signaling. Inflamm Res. 2019;68(6):511-523. PubMed PMID: 31037316.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Chicoric acid prevents methotrexate-induced kidney injury by suppressing NF-κB/NLRP3 inflammasome activation and up-regulating Nrf2/ARE/HO-1 signaling. AU - Abd El-Twab,Sanaa M, AU - Hussein,Omnia E, AU - Hozayen,Walaa G, AU - Bin-Jumah,May, AU - Mahmoud,Ayman M, Y1 - 2019/04/29/ PY - 2019/02/26/received PY - 2019/04/24/accepted PY - 2019/04/22/revised PY - 2019/5/1/pubmed PY - 2019/11/26/medline PY - 2019/5/1/entrez KW - Chicoric acid KW - Methotrexate KW - NLRP3 inflammasome KW - Nrf2 KW - ROS SP - 511 EP - 523 JF - Inflammation research : official journal of the European Histamine Research Society ... [et al.] JO - Inflamm Res VL - 68 IS - 6 N2 - 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. SN - 1420-908X UR - https://www.unboundmedicine.com/medline/citation/31037316/Chicoric_acid_prevents_methotrexate_induced_kidney_injury_by_suppressing_NF_κB/NLRP3_inflammasome_activation_and_up_regulating_Nrf2/ARE/HO_1_signaling_ L2 - https://dx.doi.org/10.1007/s00011-019-01241-z DB - PRIME DP - Unbound Medicine ER -