1. Academic Validation
  2. Renal ischemia/reperfusion injury in rats is probably due to the activation of the 5-HT degradation system in proximal renal tubular epithelial cells

Renal ischemia/reperfusion injury in rats is probably due to the activation of the 5-HT degradation system in proximal renal tubular epithelial cells

  • Life Sci. 2021 Nov 15;285:120002. doi: 10.1016/j.lfs.2021.120002.
Jiaqi Jin 1 Fan Xu 1 Yi Zhang 1 Jing Guan 1 Xiurui Liang 1 Yuxin Zhang 1 Ansheng Yuan 2 Runkun Liu 3 Jihua Fu 4
Affiliations

Affiliations

  • 1 Department of Physiology, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing 210003, China.
  • 2 School of Life Science and Technology, China Pharmaceutical University, Nanjing 211198, China.
  • 3 School of Science, China Pharmaceutical University, Nanjing 211198, China.
  • 4 Department of Physiology, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing 210003, China. Electronic address: jihua_fu@cpu.edu.cn.
Abstract

Aims: To explore the relationship between renal ischemia/reperfusion injury (RIRI) and the activation of the renal 5-HT degradation system, including 5-HT2A receptor (5-HT2AR), 5-HT synthases and monoamine oxidase-A (MAO-A).

Main methods: Rat RIRI was induced by removing the right kidney, causing ischemia of the left kidney for 45 min and reperfusion for different times. RIRI model (ischemia for 45 min and reperfusion for 24 h) was pretreated with 5-HT2AR antagonist sarpogrelate hydrochloride (SH) and the 5-HT synthase inhibitor carbidopa. In HK-2 cells, cellular damage was induced by hypoxia (24 h)/reoxygenation (12 h) (H/R) and treated with SH, carbidopa or the MAO-A Inhibitor clorgyline. Hematoxylin-eosin, immunohistochemistry, TUNEL and fluorescent probe staining, RT-qPCR, western blotting, ELISA, etc. were used in the tests.

Key findings: The development of RIRI and the emergence of the RIRI peak were consistent with renal 5-HT degradation system activation. The highest expression regions of the 5-HT degradation system overlapped with those of the most severe lesions in the kidney, which were in proximal renal tubules. Rat RIRI and HK-2 cell damage, including oxidative stress, inflammation and Apoptosis, could be almost abolished by synergistic inhibition of SH and carbidopa. Clorgyline also abolished the cellular damage induced by H/R. H/R-induced production of mitochondrial ROS in HK-2 cells was due to MAO-A-catalyzed 5-HT degradation, and 5-HT2AR was involved by mediating the expression of 5-HT synthases and MAO-A.

Significance: These findings revealed a close association between RIRI and activation of the renal 5-HT degradation system.

Keywords

5-HT degradation; 5-HT synthesis; 5-HT(2A) receptor; Reactive oxygen species; Renal ischemia/reperfusion injury.

Figures
Products