Arsenic Trioxide Combining Leflunomide Activates Nrf2-ARE-HO-1 Signaling Pathway and Protects Heart Xenografts*

Teng-da WANG; Song-lin XU; Zheng-yi YU; Shao-bin NI; Cheng ZHANG; Zhi-xing JIAO

doi:10.1007/s11655-021-3495-2

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Arsenic Trioxide Combining Leflunomide Activates Nrf2-ARE-HO-1 Signaling Pathway and Protects Heart Xenografts*

Original Articles | Updated：2021-10-18

- Arsenic Trioxide Combining Leflunomide Activates Nrf2-ARE-HO-1 Signaling Pathway and Protects Heart Xenografts*
- Chinese Journal of Integrative Medicine Vol. 27, Issue 10, Pages: 760-766(2021)
- Affiliations：
  
  Department of Urology, The First Affiliated Hospital of Harbin Medical University, Harbin (150000), China
- Author bio：
  
  Prof. JIAO Zhi-xing, E-mail: jiaozhixing@foxmail.com
- Funds：
- DOI：10.1007/s11655-021-3495-2
  CLC：
- Published：01 October 2021，
  
  Published Online：28 July 2021，
  
  Accepted：2 April 2020
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Teng-da WANG, Song-lin XU, Zheng-yi YU, et al. Arsenic Trioxide Combining Leflunomide Activates Nrf2-ARE-HO-1 Signaling Pathway and Protects Heart Xenografts*. [J]. Chinese Journal of Integrative Medicine 27(10):760-766(2021)
DOI：

Teng-da WANG, Song-lin XU, Zheng-yi YU, et al. Arsenic Trioxide Combining Leflunomide Activates Nrf2-ARE-HO-1 Signaling Pathway and Protects Heart Xenografts*. [J]. Chinese Journal of Integrative Medicine 27(10):760-766(2021) DOI： 10.1007/s11655-021-3495-2.

摘要

Abstract

Objective:

To investigate the molecular mechanisms underlying the effects of arsenic trioxide (As2O3) in combination with leflunomide on the hamster-to-rat heart xenotransplant.

Methods:

Transplantation of LVG hamster hearts to Lewis rats was performed by anastomosis of vessels in the neck using end-to-end anastomosis with a non-suture cuff technique. Four groups of recipient rats (

=6 in each) were treated with normal saline (control)

[5 mg/(kg•day) intraperitoneally]

leflunomide [5 mg/(kg•d) orally]

or leflunomide [5 mg/(kg•d)+As

[5 mg/(kg•d)] in combination. Donor hearts and/or rat spleens were harvested and analyzed 4 days after transplantation. Quantitative reverse-transcription polymerase chain reaction and Western blot analysis were performed to detect the expression of the nuclear factor erythroid-derived factor 2-related factor (Nrf2) and its target gene heme oxygenase-1 (HO-1)

Treg cell marker fork-head Box P3 (FOXP3)

apoptosis-associated proteins Bcl-2

Bax

and cleaved caspase-3. Immunohistochemical staining was used to detect the levels of inflammatory natural killer cell and macrophage infiltration

intercellular cell adhesion molecule-1 (ICAM-1) and complement C3.

Results:

Expression of Nrf2-ARE-HO-1 signaling pathway was upregulated in heart xenografts in rats treated with As

plus leflunomide compared with control rats or rats treated with either drug alone (

0.01)

and this was accompanied by an increased Treg cells in the recipient rat spleen (

0.01). In contrast

the expressions of Bax

cleaved caspase-3

ICAM-1

and complement C3

and infiltration of inflammatory cells in the xenografts were inhibited by As

plus leflunomide treatment (

0.01).

Conclusion:

Combination treatment with As

and leflunomide protected hamster heart-xenografts in recipient rats.

关键词

Keywords

arsenic trioxideleflunomideNrf2-ARE-HO-1 signaling pathwayinflammationinfiltrationxenotransplantation

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