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Original Article
- Paricalcitol prevents MAPK pathway activation and inflammation in adriamycin-induced kidney injury in rats
- Amanda Lima Deluque, Lucas Ferreira de Almeida, Beatriz Magalhães Oliveira, Cláudia Silva Souza, Ana Lívia Dias Maciel, Heloísa Della Coletta Francescato, Cleonice Giovanini, Roberto Silva Costa, Terezila Machado Coimbra
- J Pathol Transl Med. 2024;58(5):219-228. Published online August 27, 2024
- DOI: https://doi.org/10.4132/jptm.2024.07.12
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Abstract
PDF - Background
Activation of the mitogen-activated protein kinase (MAPK) pathway induces uncontrolled cell proliferation in response to inflammatory stimuli. Adriamycin (ADR)-induced nephropathy (ADRN) in rats triggers MAPK activation and pro-inflammatory mechanisms by increasing cytokine secretion, similar to chronic kidney disease (CKD). Activation of the vitamin D receptor (VDR) plays a crucial role in suppressing the expression of inflammatory markers in the kidney and may contribute to reducing cellular proliferation. This study evaluated the effect of pre-treatment with paricalcitol on ADRN in renal inflammation mechanisms.
Methods
Male Sprague-Dawley rats were implanted with an osmotic minipump containing activated vitamin D (paricalcitol, Zemplar, 6 ng/day) or vehicle (NaCl 0.9%). Two days after implantation, ADR (Fauldoxo, 3.5 mg/kg) or vehicle (NaCl 0.9%) was injected. The rats were divided into four experimental groups: control, n = 6; paricalcitol, n = 6; ADR, n = 7 and, ADR + paricalcitol, n = 7.
Results
VDR activation was demonstrated by increased CYP24A1 in renal tissue. Paricalcitol prevented macrophage infiltration in the glomeruli, cortex, and outer medulla, prevented secretion of tumor necrosis factor-α, and interleukin-1β, increased arginase I and decreased arginase II tissue expressions, effects associated with attenuation of MAPK pathways, increased zonula occludens-1, and reduced cell proliferation associated with proliferating cell nuclear antigen expression. Paricalcitol treatment decreased the stromal cell-derived factor 1α/chemokine C-X-C receptor type 4/β-catenin pathway.
Conclusions
Paricalcitol plays a renoprotective role by modulating renal inflammation and cell proliferation. These results highlight potential targets for treating CKD.
Review
- Oncogenic osteomalacia.
- Yong Koo Park
- Korean J Pathol. 2006;40(1):1-8.
- 1,619 View
- 19 Download
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Abstract
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- An unusual and rare presentation of osteomalacia results from the paracrine effect of a localized bone or soft tissue neoplasm. In this syndrome, known as tumor induced osteomalacia or oncogenic osteomalacia, a neoplasm synthesizes and secretes a circulating compound, known as phosphatonin, which acts on the kidney leading to phosphate wasting. Oncogenic osteomalacia can be caused by a wide variety of neoplasm, although they are usually primary soft tissue or bone tumors. Most commonly the causative neoplasm is a benign or low-grade malignant vascular or fibrous tissue tumor. Complete removal of the offending neoplasm completely reverses the osteomalacia. If successful, the osteomalacia resolves. However, incomplete removal of the neoplasm necessitates treatment with phosphate and Vitamin D3 to ameliorate the skeletal disease.
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