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Abstract: TH-PO225

Mitophagy Is Activated to Protect against Iodionated Contrast-Induced AKI

Session Information

Category: Acute Kidney Injury

  • 001 AKI: Basic

Authors

  • Duan, Shaobin, Department of Nephrology, The Second Xiangya Hospital, Central South University, Changsha410011, China, Changsha, China
  • Lei, Rong, Department of Nephrology, The Second Xiangya Hospital, Central South University, Changsha410011, China, Changsha, China
  • Zhao, Fei, Department of Nephrology, The Second Xiangya Hospital, Central South University, Changsha410011, China, Changsha, China
  • Luo, Min, Department of Nephrology, The Second Xiangya Hospital, Central South University, Changsha410011, China, Changsha, China
  • Li, Wei Xu, Department of Nephrology, The Second Xiangya Hospital, Central South University, Changsha410011, China, Changsha, China
  • Cheng, Wei, Department of Nephrology, The Second Xiangya Hospital, Central South University, Changsha410011, China, Changsha, China
  • Tang, Chengyuan, Department of Nephrology, The Second Xiangya Hospital, Central South University, Changsha410011, China, Changsha, China
  • Dong, Zheng, Georgia Regents University, Augusta, Georgia, United States
  • Sun, Lin, Department of Nephrology, The Second Xiangya Hospital, Central South University, Changsha410011, China, Changsha, China
  • Liu, Hong, Department of Nephrology, The Second Xiangya Hospital, Central South University, Changsha410011, China, Changsha, China
Background

Contrast induced-acute kidney injury (CIAKI) is one of the most commmon causes of acute kidney injury in hospitalized patients, but the underlying pathogenesis is poorly understood. And there are little reports about the regulation and role of mitophagy in CIAKI.

Methods

The establishment of damaged cells model was performed.The cell viability, expression of LC3II/I and parkin, cleaved caspase 3, mitochondrial ROS, mitochondrial membrane potential, colocalization of LC3-FITC and parkin-FITC with mitotracker-red mitochondria, formation of autophagosome and mitophagy were measured. The Rapamycin (Rap) and 3-Methyladenine (3-Ma) were used to enhance and inhibit the formation of autophagososmes respectively.
Male SD rats were deprived of water for 48 h and followed by furosemide (10 ml/kg) for 20 minutes before iohexol (15 ml/kg) administration to build CIAKI models. Pretreatmemt with Rap or 3-Ma was used at 1 h before iohexol injection. Serum creatinine were measured before and 24 h after the injection of iohexol. Kidney tissues were collected for HE staining, electron microscope examination and expression of LC3II/I, P62, Cleaved Caspase3, Parkin.

Results

Iohexol and iodixanol dose-dependently decreased cell ciability, also induced mitochondrial damage, cell apoptosis and mitophagy. Enhancing mitophagy with Rap markedly increased expression of LC3II, Parkin and formation of autophagosome and mitophagy, reversed iohexol induced apoptosis. Rap also significantly decreased expression of cleaved caspase 3 and serum creatinine. LC3-FITC and parkin-FITC puncta colocalization with mitotracker-red mitochondria were increased. In contrast, inhibiton of mitophagy with 3-Ma displayed increased serum creatinine, apoptosis and expression of cleaved caspase 3, decreased expression of LC3II and formation of autophagosome and mitophagy, compared with iohexol group.

Conclusion

Autophagy and mitophagy play an important role in mitochondrial quality control, tubular cell survival, and renal function during CIAKI. Enhancing mitophagy may offer a novel therapy for CIAKI.

Funding

  • Government Support - Non-U.S.