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Current Vascular Pharmacology

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ISSN (Print): 1570-1611
ISSN (Online): 1875-6212

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Research Article

Lanthanum Hydroxide and Chronic Kidney Disease Mineral and Bone Disorder: A Rat Model

Author(s): Chao Gu, Ting Zhang, Yuan Gao, Xiaojia Li, Xiaorong Yuan, Qiwen Wang, Hong Liu, Ruilan Han and Gang LI*

Volume 22, Issue 2, 2024

Published on: 13 November, 2023

Page: [122 - 136] Pages: 15

DOI: 10.2174/0115701611254269231105063028

Price: $65

Abstract

Objective: To investigate the pharmacological effects and molecular mechanisms of lanthanum hydroxide(LH) on ectopic mineralization of soft tissue and abnormal bone in rats with acute kidney injury(AKI).

Methods: Wistar rats were modeled by 5/6 nephrectomy. After the operation, the rats were divided into different groups, the biochemical indexes of serum collected at different times. LH was administered by intragastric tube at doses of 0.4, 0.2, and 0.1g/kg, respectively. Rats were sacrificed in the 16th week after LH treatment. Observation of pathological changes in tissues were made by specific staining. Western Blot, Real-Time Quantitative PCR, and immunohistochemistry techniques were used to detect the impact on pathway-related proteins.

Results: Compared with the control group (no LH administered), the serum phosphate level of the LH group was significantly reduced (p<0.01), calcification of the thoracic aorta was reduced (p<0.05, p<0.01) (Serum biochemical tests before dosing and during drug treatment cycles), renal fibrosis was improved (p<0.01), nuclear entry of nuclear factor kappa-B (NF-κB) was reduced (p<0.01), and the expression of the smooth muscle protein 22α (SM22α) was significantly increased (p<0.01). The expression of osteogenic marker genes was decreased. In addition, compared with the controls, the receptor activator for nuclear factor-κB ligand/osteoprotegerin (RANKL/OPG) ratio of the femur in the model group was increased (p<0.05).

Conclusion: LH can inhibit the occurrence and development of vascular calcification and bone abnormalities in AKI rats by inhibiting the NF-κB and RANKL/OPG signaling pathways.

Keywords: Hyperphosphatemia, vascular smooth muscle cells, lanthanum hydroxide, chronic kidney disease-mineral and bone disorder, nuclear factor kappa-B signaling pathway, RANKL signaling pathway.

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