AdipoRon, an adiponectin receptor agonist, protects contrast-induced nephropathy by suppressing oxidative stress and inf
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ORIGINAL ARTICLE
AdipoRon, an adiponectin receptor agonist, protects contrast‑induced nephropathy by suppressing oxidative stress and inflammation via activation of the AMPK pathway Daqian Gu1,2,3 · Yu Shi1,2,3 · Zhengfan Gong1,2,3 · Tianyang Xia1,2,3 · Hongmei Ren1,2,3 · Duofen He1,2,3 · Jian Yang4 · Yu Han1,2,3 · Chunyu Zeng1,2,3 Received: 9 August 2019 / Accepted: 2 July 2020 © Japanese Society of Nephrology 2020
Abstract Background Contrast-induced nephropathy (CIN), a complication caused by using contrast medium during diagnostic and interventional procedures, occurs frequently and lacks effective treatment. AdipoRon, the agonist of adiponectin receptors, has been shown to benefit many organs including the kidney. This study aimed to investigate the role of AdipoRon in treating CIN. Methods CIN model was established via infusing iopromide (1.8 g/kg) in Sprague–Dawley (SD) rats; NRK52E cells were treated with iopromide (5–50 μM). Renal function, renal histopathology, levels of lactate dehydrogenase (LDH) release, cell vitality, oxidative stress and inflammatory markers were measured to evaluate the protective effects of AdipoRon. The level of pAMPK/AMPK was determined by western blot. Results AdipoRon (50 mg/kg) significantly reversed serum creatinine, blood urea nitrogen, creatinine clearance and urinary kidney injury molecule-1 levels induced by iopromide in SD rats. Besides, it decreased the renal injury score and apoptosis of renal cells. AdipoRon also reversed the changes of antioxidant markers, pro-oxidant and inflammatory markers induced by iopromide. Moreover, the in vitro studies showed that AdipoRon decreased LDH release and increased cell vitality in NRK52E cells treated with iopromide. Then, we demonstrated that the protection of AdipoRon was accompanied by augmented AMPK phosphorylation. Both in vivo and in vitro studies demonstrated that compound c, an AMPK inhibitor, reversed the AdipoRon-mediated improvement in the CIN model. Conclusion Our data indicate that AdipoRon protects against the CIN by suppressing oxidative stress and inflammation via activating the AMPK pathway, showing that AdipoRon might be a potential candidate for the prevention and therapy of CIN. Keywords AdipoRon · Contrast-induced nephropathy · AMPK · Oxidative stress · Inflammation
Introduction
Daqian Gu and Yu Shi contributed equally to this work. Electronic supplementary material The online version of this article (https://doi.org/10.1007/s10157-020-01944-2) contains supplementary material, which is available to authorized users. * Yu Han hanc2‑[email protected] * Chunyu Zeng [email protected] Extended author information available on the last page of the article
Contrast-induced nephropathy (CIN) is a complication caused by contrast medium (CM) administration during diagnostic and interventional procedures; it is defined as an increase in serum creatinine concentration of more than 44.2 μmol/l or 25% above baseline within 48 or 72 h after administration of CM [1]. The nephrotoxic effects of CM have been demonst
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