Korean J Intern Med.  2021 Mar;36(Suppl 1):S180-S195. 10.3904/kjim.2019.413.

L-carnitine treatment attenuates renal tubulointerstitial fibrosis induced by unilateral ureteral obstruction

• Zhao HY
• Li HY
• Jin J
• Jin JZ
• Zhang LY
• Xuan MY
• Jin XM
• Jiang YJ
• Zheng HL
• Jin YS
• Jin YJ
• Choi BS
• Yang CW
• Piao SG
• Li C

• KMID: 2513826
• DOI: http://doi.org/10.3904/kjim.2019.413

Abstract

Background/Aims
Accumulating evidence indicates that L-carnitine (LC) protects against multiorgan damage through its antioxidant properties and preservation of the mitochondria. Little information is available about the effects of LC on renal fibrosis. This study examined whether LC treatment would provide renoprotection in a rat model of unilateral ureteral obstruction (UUO) and in vitro.
Methods
Sprague-Dawley rats that underwent UUO were treated daily with LC for 7 or 14 days. The influence of LC on renal injury caused by UUO was evaluated by histopathology, and analysis of gene expression, oxidative stress, mitochondrial function, programmed cell death, and phosphatidylinositol 3-kinase (PI3K)/ AKT/forkhead box protein O 1a (FoxO1a) signaling. In addition, H₂O₂-exposed human kidney cells (HK-2) were treated with LC.
Results
LC treatment inhibited expression of proinflammatory and profibrotic cytokines, and was followed by a significant attenuation of tubulointerstitial inflammation and fibrosis. The increased oxidative stress caused by UUO was associated with mitochondrial dysfunction and excessive apoptosis and autophagy via PI3K/AKT/FoxO1a-dependent signaling, and this was abrogated by administration of LC. In H₂O₂-exposed HK-2 cells, LC decreased intracellular production of reactive oxygen species, and suppressed expression of profibrotic cytokines and reduced the number of apoptotic cells.
Conclusions
LC protects against the progression of tubulointerstitial fibrosis in an obstructed kidney.

Keyword

L-carnitine; Unilateral ureteral obstruction; Oxidative stress; Autophagy; Mitochondria