Renoprotective effects of paricalcitol on gentamicin-induced kidney injury in rats.

Abstract

Vitamin D is thought to exert a protective effect on renal disease progression, but the underlying molecular mechanism remains unclear. We investigated whether paricalcitol ameliorates tubular dysfunction and fibrosis in gentamicin (GM)-induced renal injury. Two groups of rats were treated with GM (100 mg x kg(-1) x day(-1)), one of which was cotreated with paricalcitol (0.3 microg x kg(-1) x day(-1)) for 14 days and the other was not. The control group was treated with vehicle only. HK-2 cells were cultured with GM in the absence or presence of paricalcitol. Paricalcitol restored impaired renal function and the downregulated renal sodium transporters and aquaporin-1 expression caused by GM. ED-1-expressing monocyte/macrophage accumulation induced by GM was attenuated by paricalcitol treatment. Paricalcitol prevented upregulated inflammatory cytokines (TNF-alpha, IL-1beta, INF-gamma) and adhesion molecules (monocyte chemoattractant protein-1, ICAM-1, VCAM-1) induced by GM. In addition, paricalcitol effectively reversed TGF-beta1-induced epithelial-to-mesenchymal transition (EMT) process and extracellular matrix accumulation in GM-induced nephropathy. Increased collagen deposition and fibrosis in GM-treated kidney were ameliorated by paricalcitol. Paricalcitol also attenuated the upregulated NF-kappaB and phosphorylated ERK1/2 expression in HK-2 cells cultured with GM. In conclusion, paricalcitol prevents GM-induced renal injury by inhibiting renal inflammation and fibrosis, the mechanism of which is the interruption of NF-kappaB/ERK signaling pathway and preservation of tubular epithelial integrity via inhibiting EMT process.

• Authors: Jeong Woo Park, Eun Hui Bae, In Jin Kim, Seong Kwon Ma, Chan Choi, JongUn Lee, Soo Wan Kim
• Journal: American journal of physiology. Renal physiology (Am J Physiol Renal Physiol) Vol. 298 Issue 2 Pg. F301-13 (Feb 2010) ISSN: 1522-1466 [Electronic] United States
• PMID: 19940033 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Aqp1 protein, rat
• Bone Density Conservation Agents
• Carrier Proteins
• Cell Adhesion Molecules
• Cytokines
• Ergocalciferols
• Gentamicins
• Inflammation Mediators
• NF-kappa B
• Transforming Growth Factor beta1
• Aquaporin 1
• paricalcitol
• Sodium
• Extracellular Signal-Regulated MAP Kinases

Topics

• Animals
• Aquaporin 1 (metabolism)
• Bone Density Conservation Agents (pharmacology)
• Carrier Proteins (metabolism)
• Cell Adhesion Molecules (metabolism)
• Cell Line
• Cytokines (metabolism)
• Ergocalciferols (pharmacology)
• Extracellular Signal-Regulated MAP Kinases (metabolism)
• Fibrosis (prevention & control)
• Gentamicins (pharmacokinetics)
• Inflammation Mediators (metabolism)
• Kidney Diseases (chemically induced, prevention & control)
• Kidney Tubules (cytology, drug effects, metabolism)
• Kidney Tubules, Proximal (drug effects, pathology)
• Male
• NF-kappa B (metabolism)
• Nephritis (chemically induced, prevention & control)
• Rats
• Rats, Sprague-Dawley
• Sodium (metabolism)
• Transforming Growth Factor beta1 (metabolism)