Abstract
Chronic kidney disease–mineral and bone metabolism disorder (CKD-MBD) is a common chronic kidney disease (CKD)-associated complication that increases the risk of metabolic bone diseases, fractures, osteoblastic trans-differentiation of vascular smooth muscle cells, and cardiovascular events. SD rats were randomised into five groups with six rats per group: sham, CKD, CKD + advanced glycosylation end products (AGEs), CKD + Quercetin, and CKD + AGEs + Quercetin. The protective effects of AGEs and quercetin on SD rats were assessed by renal function, renal pathology, bone metabolism, osteoblastic trans-differentiation of vascular smooth muscle cells, and the receptor for AGE (RAGE) expression. Compared with the control group, rats in the CKD and CKD + AGEs groups had significantly lower body weight, higher serum AGEs levels, impaired renal function, increased levels of oxidative stress in the kidney and bone marrow tissues, lower femoral bone mineral density (BMD), callus mineralised volume fraction (mineralised bone volume/total volume), abnormal serum bone metabolism levels, and increased renal tissue, bone tissue, and abdominal aorta RAGE expression levels, and the RAGE downstream NF-κB signalling pathway was upregulated. Quercetin significantly improved renal dysfunction, attenuated serum AGE levels, reduced oxidative stress levels in the kidney and bone marrow tissues, and downregulated RAGE expression in the kidney, bone, and abdominal aorta and the RAGE downstream NF-κB signalling pathway in rats with CKD. AGEs are involved in the pathogenesis of CKD-MBD by promoting osteoblastic trans-differentiation of vascular smooth muscle cells and abnormal bone metabolism. Quercetin plays a role in the prevention and treatment of CKD-MBD by reducing the production of AGEs.
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The datasets used and/or analysed in the current study are available from the corresponding author upon reasonable request.
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This study was supported by the CKD-MBD Youth Research Fund Project 2020 (No. NBPIA20QC0304).
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Yujie Wang and Chenggang Hu drafted the article and performed data analysis; Yujie Wang revised the article, approved the final version, and was responsible for all aspects of the work. All the authors agreed to the submission of this manuscript. The authors declare that all data were generated in-house and that no paper mill was used.
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All procedures were performed in accordance with the Guide for the Care and Use of Laboratory Animals published by the National Institutes of Health (NIH Publication No. 85–23, revised 1996). The study protocol was reviewed and approved by the ethics committee of The Affiliated Hospital of Southwest Medical University according to the guidelines for the ethical review of animal welfare.
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Wang, Y., Hu, C., Cao, L. et al. Advanced glycosylation end products promote the progression of CKD-MBD in rats, and its natural inhibitor, quercetin, mitigates disease progression. Naunyn-Schmiedeberg's Arch Pharmacol (2024). https://doi.org/10.1007/s00210-024-03217-1
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DOI: https://doi.org/10.1007/s00210-024-03217-1