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NecroX-7 Ameliorate FK506-Induced Nephrotoxicity in LLC-PK1 Cells (Pig Kidney Epithelial Cells)

H. J. Jang

Surgery, University of Ulsan, Gangneung Asan Hospital, Gangneung, Korea, Republic of

Meeting: 2022 American Transplant Congress

Abstract number: 1292

Keywords: Apoptosis, FK506, Inflammation, Nephrotoxicity

Topic: Basic Science » Basic Science » 12 - Immunosuppression & Tolerance: Preclinical & Translational Studies

Session Information

Session Name: Immunosuppression & Tolerance: Preclinical & Translational Studies

Session Type: Poster Abstract

Date: Monday, June 6, 2022

Session Time: 7:00pm-8:00pm

 Presentation Time: 7:00pm-8:00pm

Location: Hynes Halls C & D

*Purpose: Tacrolimus (FK506) is an immunosuppressant agent that is frequently used to prevent rejection of solid organs upon transplant. However, nephrotoxicity due to apoptosis and inflammatory response mediated by FK506 limit its usefulness. Cyclopentylamino carboxymethylthiazolylindole (NecroX) is a class of indole-derived, cell-permeable, antioxidant molecules that exhibit cytoprotective effects in cells acting as a scavenger of reactive oxygen species (ROS). In the present study, the protective effect of necrox-7 against FK506-induced damage in LLC-PK1 pig kidney epithelial cells was investigated.

*Methods: LLC-PK1 cells were exposed to FK506 with necrox-7, and cell viability was measured. Western blotting and RT-PCR analyses evaluated protein or gene expression of MDA, HO-1, Bcl-2, Bax, caspase-3, interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), kidney injury molecule-1 (KIM-1), toll-like receptor-4 (TLR-4), and high mobility group box 1 protein (HMGB1) expression were assessed. The number of apoptotic cells was measured using an annexin V/PI staining with flow cytometry.

*Results: Reduction in cell viability by 50mM FK506 was ameliorated significantly by cotreatment with necrox-7. MDA, KIM-1, IL-6, TNF-α, BAX, caspase-3, TLR-4 and HMGB1, increased markedly in LLC-PK1 cells treated with FK506 and significantly decreased after cotreatment with necrox-7. HO-1 and Bcl-2 significantly increased in LLC-PK1 cells treated with FK506 after cotreatment with necrox-7. Moreover, flow cytometry assay showed that apoptotic cell death was increased by FK506 treatment, whereas it was significantly decreased after cotreatment with necrox-7.

*Conclusions: These results collectively provide therapeutic evidence that necrox-7 ameliorates the FK506-induced renal damage via antioxidant effect and inhibiting apoptosis and inflammation.

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To cite this abstract in AMA style:

Jang HJ. NecroX-7 Ameliorate FK506-Induced Nephrotoxicity in LLC-PK1 Cells (Pig Kidney Epithelial Cells) [abstract]. Am J Transplant. 2022; 22 (suppl 3). https://atcmeetingabstracts.com/abstract/necrox-7-ameliorate-fk506-induced-nephrotoxicity-in-llc-pk1-cells-pig-kidney-epithelial-cells/. Accessed May 29, 2025.

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