We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Pretreatment with paricalcitol attenuates inflammation in ischemia–reperfusion injury via the up-regulation of cyclooxygenase-2 and prostaglandin E2.
- Authors
Hwang, Hyeon Seok; Yang, Keum Jin; Park, Ki Cheol; Choi, Hyun Soo; Kim, So Hee; Hong, Sung Youp; Jeon, Byeong Hwa; Chang, Yoon Kyung; Park, Cheol Whee; Kim, Suk Young; Lee, Sang Ju; Yang, Chul Woo
- Abstract
Background The effect of paricalcitol on renal ischemia–reperfusion injury (IRI) has not been investigated. We examined whether paricalcitol is effective in preventing inflammation in a mouse model of IRI, and evaluated the cyclooxygenase-2 (COX-2) and prostaglandin E2 (PGE2) pathways as a protective mechanism of paricalcitol. Methods Paricalcitol (0.3 μg/kg) was administered to male C57BL/6 mice 24 h before IRI. Bilateral kidneys were subjected to 23 min of ischemia, and mice were killed 72 h after IRI. The effects of paricalcitol on renal IRI were evaluated in terms of renal function, tubular necrosis, apoptotic cell death, inflammatory cell infiltration and inflammatory cytokines. The effects of paricalcitol on COX-2, PGE2 and its receptors were investigated. Results Paricalcitol pretreatment improved renal function (decreased blood urea nitrogen and serum creatinine levels), tubular necrosis and apoptotic cell death in IRI-mice kidneys. The infiltration of inflammatory cells (T cells and macrophages), and the production of proinflammatory cytokines (RANTES, tumor necrosis factor-α, interleukin-1β and interferon-γ) were reduced in paricalcitol-treated mice with IRI. Paricalcitol up-regulated COX-2 expression, PGE2 synthesis and mRNA expression of receptor subtype EP4 in post-ischemic renal tissue. The cotreatment of a selective COX-2 inhibitor with paricalcitol restored functional injury and tubular necrosis in paricalcitol-treated mice with IRI. Conclusions Our study demonstrates that paricalcitol pretreatment prevents renal IRI via the inhibition of renal inflammation, and the up-regulation of COX-2 and PGE2 is one of the protective mechanisms of paricalcitol in renal IRI.
- Subjects
REPERFUSION injury; DINOPROSTONE; CYCLOOXYGENASES regulation; BLOOD urea nitrogen; TUMOR necrosis factors; INFLAMMATION; KIDNEY physiology
- Publication
Nephrology Dialysis Transplantation, 2013, Vol 28, Issue 5, p1156
- ISSN
0931-0509
- Publication type
Article
- DOI
10.1093/ndt/gfs540