Affiliation:
1. Northeast Agricultural University
Abstract
Abstract
Background: Aristolochic acid I (AA-I) can damage the structure and function of kidney, but there are few prevention strategies at present. In this study, we investigated the protective effects and mechanism of Rehmannia glutinosa extract-catalpol (CAT) on renal injury caused by AA-I.
Methods: In vitro, NRK-52E cells were administered with AA-I (40 μM) or/and CAT (10 μM, 5 μM) for 24 h. In vivo, C57BL/6NJ male mice were administered with AA-I (10 mg/kg) or/and CAT (100 mg/kg, 10 mg/kg) for 28 d. Clinical symptoms, histopathology, Elisa, quantitative RT-PCR, Westernblot, immunocytochemistry, immunofluorescence and flow cytometry were used to evaluate the protective effect of CAT on renal injury.
Results: In the model group, the body weight and renal function of mice decreased significantly, and the pathological damage of renal tissue was obvious. Compared with the model group, CAT can significantly improve the kidney structure and function. Activate NF-E2-related-factor-2 (Nrf2) signal pathway, increase antioxidant enzyme activity and decrease ROS and MDA levels. CAT can also inhibit the nuclear-factor-kappa-B (NF-κB) signaling pathway and reduce the expression of Cyt-c, TNF-α and pro-IL-1β. In addition, CAT can reduce Ca2+ concentration, endoplasmic reticulum (ER) stress and mitochondrial damage, thus reducing mitochondrial pathway apoptosis and cell apoptosis rate. And both Nrf2 and NF-κB are the main targets of CAT in alleviating AA-I-induced renal injury.
Conclusion: CAT can attenuate the damage of renal structure and function through Nrf2/NF-κB pathways. CAT can inhibit inflammation and oxidative stress, further reducing the mitochondrial pathway apoptosis and endoplasmic reticulum stress pathway apoptosis.
Publisher
Research Square Platform LLC
Reference44 articles.
1. 'Protective Effect of Nebivolol against Oxidative Stress Induced by Aristolochic Acids in Endothelial Cells';Antoine MH;Toxins,2022
2. 'Determination of Aristolochic Acids in Vegetables: Nephrotoxic and Carcinogenic Environmental Pollutants Contaminating a Broad Swath of the Food Supply and Driving Incidence of Balkan Endemic Nephropathy';Au CK;Chemical Research in Toxicology,2020
3. 'Catalpol ameliorates type II collagen-induced arthritis in rats and inhibits LPS-stimulated inflammatory response in SW982 human synovial cells';Bi JJ;Journal of Functional Foods,2019
4. Chan, C. K., Y. S. Liu, N. M. Pavlovic, and W. Chan. 2019. 'Aristolochic Acids: Newly Identified Exposure Pathways of this Class of Environmental and Food-Borne Contaminants and its Potential Link to Chronic Kidney Diseases', Toxics, 7.
5. 'Inhibiting nuclear factor erythroid 2 related factor 2-mediated autophagy in bovine mammary epithelial cells induces oxidative stress in response to exogenous fatty acids';Chang RX;Journal of Animal Science and Biotechnology,2022