Paricalcitol Attenuates Contrast-Induced Acute Kidney Injury by Regulating Mitophagy and Senescence

Eunjin Bae,Se-Ho Chang,Jin Hyun Kim,Ha Nee Jang,Seunghye Lee,Dong Jun Park,Myeong Hee Jung,Si Jung Jang,Sehyun Jung,Tae Won Lee,Ralf Braun

doi:10.1155/2020/7627934

Abstract

Contrast-induced acute kidney injury (CI-AKI) is the third most common cause of hospital-acquired renal failure, with an incidence of 11%. However, the disease mechanism remains unclear, and no effective treatment is available. Paricalcitol has been reported to be effective in animal models of kidney injury. We hypothesized that paricalcitol could play a renoprotective role against CI-AKI. Rats were divided into control, paricalcitol, contrast, and paricalcitol-plus-contrast groups. We used a previously published protocol to produce CI-AKI. Paricalcitol (0.3 μg/kg) was administered intraperitoneally before 24 h and 30 min before indomethacin. We used HK-2 cells to evaluate the effects of paricalcitol on mitophagy and senescence. Ioversol triggered renal dysfunction, increasing blood urea nitrogen and serum creatinine. Significant tubular damage, increased 8-OHdG expression, and apoptosis were apparent. Ioversol injection induced high expression levels of the mitophagy markers Pink1, Parkin, and LC3 and the senescence markers β-galactosidase and p16INK4A. Paricalcitol pretreatment prevented renal dysfunction and reduced tissue damage by reducing both mitophagy and senescence. Cellular morphological changes were found, and expression of LC3B and HMGB1 was increased by ioversol in HK-2 cells. Paricalcitol countered these effects. This study showed that mitochondria might drive injury phenotypes in CI-AKI, and that paricalcitol protects against CI-AKI by decreasing mitochondrial damage.

Highlights

Radiocontrast agents are diagnostically and therapeutically indispensable
To confirm the protective effects of paricalcitol in terms of renal tubular damage, we explored whether paricalcitol would reduce ioversolinduced toxicity toward HK-2 cells
To examine whether paricalcitol protects against renal tubular cell injury caused by contrast, by reducing mitochondrial damage including mitophagy and mitochondrial oxidative stress, HK-2 cells were costained with greenfluorescing MitoTracker and red-fluorescing LysoTracker in the ioversol and ioversol with paricalcitol groups

Summary

Introduction

Radiocontrast agents are diagnostically and therapeutically indispensable. the incidence of adverse events is 1–15% despite the introduction of newer and safer materials [1]. Contrast-induced acute kidney injury (CI-AKI), a severe adverse event, refers to AKI that develops after intravascular administration of contrast media (several definitions have been published). Several experimental studies have shown that paricalcitol (19-nor-1,25-dihydroxyvitamin D2) has beneficial effects in several models of AKI; it exhibits anti-inflammatory, antiapoptotic, and antifibrotic actions [16,17,18,19,20]. This is the first study to explore whether paricalcitol protects against experimental CI-AKI in rodents

Materials and Methods

Results

Discussion

Conflicts of Interest