Sanaa M Abd El-Twab1, Omnia E Hussein1, Walaa G Hozayen2,3, May Bin-Jumah4, Ayman M Mahmoud5. 1. Physiology Division, Department of Zoology, Faculty of Science, Beni-Suef University, Beni-Suef, Egypt. 2. Biochemistry Division, Chemistry Department, Faculty of Science, Beni-Suef University, Beni-Suef, Egypt. 3. Biotechnology and Life Sciences Department, Faculty of Postgraduate Studies for Advanced Sciences (PSAS), Beni-Suef University, Beni-Suef, Egypt. 4. Department of Biology, College of Science, Princess Nourah bint Abdulrahman University, Riyadh, Saudi Arabia. 5. Physiology Division, Department of Zoology, Faculty of Science, Beni-Suef University, Beni-Suef, Egypt. ayman.mahmoud@science.bsu.edu.eg.
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.
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: Saleem H Aladaileh; Omnia E Hussein; Mohammad H Abukhalil; Sultan A M Saghir; May Bin-Jumah; Manal A Alfwuaires; Mousa O Germoush; Amer A Almaiman; Ayman M Mahmoud Journal: Antioxidants (Basel) Date: 2019-09-26
Authors: Saleem H Aladaileh; Mohammad H Abukhalil; Sultan A M Saghir; Hamza Hanieh; Manal A Alfwuaires; Amer A Almaiman; May Bin-Jumah; Ayman M Mahmoud Journal: Biomolecules Date: 2019-08-05
Authors: Mousa O Germoush; Hassan A Elgebaly; Sherif Hassan; Emadeldin M Kamel; May Bin-Jumah; Ayman M Mahmoud Journal: Antioxidants (Basel) Date: 2019-12-26