Abstract: FR-PO353

Dysfunction of the Intestinal Carnitine/Organic Cation Transporter 1 in CKD Impairs an Antioxidant Effect of Ergothioneine

Session Information

Category: Chronic Kidney Disease (Non-Dialysis)

  • 308 CKD: Mechanisms of Tubulointerstitial Fibrosis

Authors

  • Shinozaki, Yasuyuki, Kanazawa University, Ishikawa, Japan
  • Furuichi, Kengo, Kanazawa University, Ishikawa, Japan
  • Toyama, Tadashi, Kanazawa University, Ishikawa, Japan
  • Kitajima, Shinji, Kanazawa University, Ishikawa, Japan
  • Hara, Akinori, Kanazawa University, Ishikawa, Japan
  • Iwata, Yasunori, Kanazawa University, Ishikawa, Japan
  • Sakai, Norihiko, Kanazawa University, Ishikawa, Japan
  • Shimizu, Miho, Kanazawa University, Ishikawa, Japan
  • Wada, Takashi, Kanazawa University, Ishikawa, Japan
Background

Carnitine/organic cation transporter 1 (OCTN1) is a specific transporter of the food-derived antioxidant, ergothioneine (ERGO). ERGO absorbed by intestinal OCTN1 is distributed systemically through the bloodstream and incorporated into each organ by OCTN1. The OCTN1–ERGO axis is an adaptive antioxidant system that protects against further damage caused by oxidative stress. However, the role of OCTN1–ERGO axis in chronic kidney disease (CKD) progression remains unclear.

Methods

The ability of the intestine to absorb ERGO and OCTN1 expression were evaluated in CKD mice using the everted sac method, RT-PCR, western blot and immunohistochemistry. To identify the role of the OCTN1–ERGO axis in CKD, we evaluated kidney damage and oxidative stress in OCTN1-knockout CKD mice. To assess the protective effects of ERGO in CKD, we checked the antioxidant effect of ERGO using mProx24 cells. Moreover, we measured ERGO levels in the blood of CKD patients.

Results

Although the mRNA and protein expression of OCTN1 did not change as CKD progressed, the localization of OCTN1 to the apical cellular membrane was reduced in the intestines of CKD mice. OCTN1-knockout CKD mice showed enhanced kidney damage, interstitial fibrosis, and oxidative stress. An in vitro study using mProx24 cells treated with indoxyl sulfate, which was pretreated with ERGO, revealed a dose-dependent attenuation of oxidative stress. In CKD patients, ERGO levels decreased as CKD progressed and that there was a positive correlation between ERGO and eGFR levels. ERGO levels were restored 10 months after kidney transplants in three patients.

Conclusion

CKD attenuated the function of the OCTN1–ERGO axis because of the dysfunction of intestinal OCTN1. These results suggested that a novel inter-organ interaction mediated by transporters is associated with CKD progression.