Title:Lanthanum Hydroxide and Chronic Kidney Disease Mineral and Bone
Disorder: A Rat Model
Volume: 22
Issue: 2
Author(s): Chao Gu, Ting Zhang, Yuan Gao, Xiaojia Li, Xiaorong Yuan, Qiwen Wang, Hong Liu, Ruilan Han and Gang LI*
Affiliation:
- Department of Pharmacology, College of Pharmacy, the Inner Mongolian Medical University, Jinshan Development, Hohhot, 010110, Inner Mongolia Autonomous Region, China
Keywords:
Hyperphosphatemia, vascular smooth muscle cells, lanthanum hydroxide, chronic kidney disease-mineral and bone disorder, nuclear factor kappa-B signaling pathway, RANKL signaling pathway.
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.
