Paricalcitol pretreatment attenuates renal ischemia/reperfusion injury by inhibiting p38 MAPK and activating PI3K/Akt signaling pathways

Abstract

Objective: This study aimed to investigate the renoprotective effects of paricalcitol, a synhetic vitamin D analog, through its possible roles on p38 MAPK and PI3K/Akt signaling pathways to prevent oxidative stress, inflammation and apoptosis during renal I/R. Materials and methods: Total 20 kidney tissues of sham (n = 6), subjected to renal I/R bilaterally for 45 min ischemia followed by 24 h reperfusion (n = 7) and paricalcitol (0.3 µg/kg, ip) pretreated Wistar albino rats (n = 7) were used in this study. Interstitial inflammation and active caspase-3 expression were evaluated histologically. TNF-?, IL-1ß, kidney injury molecule-1 (KIM-1), MDA and SOD activity in kidneys were analysed biochemically. Furthermore, activation of p38 MAPK, PI3K/Akt signaling pathways and NF?B p65 were evaluated by western blot. Results: Paricalcitol pretreatment significantly reduced interstitial inflammation during renal I/R, which was consistent with decreased tumor TNF-?, IL-1ß, active caspase-3 and KIM-1 expression. Paricalcitol also reduced MDA level and attenuated the reduction of SOD activity in the kidney during I/R. Moreover, paricalcitol could suppress the p38 MAPK and NF?B p65, and also activate PI3K/Akt signaling pathway during renal I/R. Conclusion: All these findings indicate that paricalcitol may be an effective practical strategy to prevent renal I/R injury. © 2019 De Gruyter. All rights reserved.