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

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From: Chinese Journal of Integrative Medicine(Vol. 27, Issue 10)
Publisher: Springer
Document Type: Report; Brief article
Length: 309 words

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Keywords: arsenic trioxide; leflunomide; Nrf2-ARE-HO-1 signaling pathway; inflammation; infiltration; xenotransplantation Abstract Objective To investigate the molecular mechanisms underlying the effects of arsenic trioxide ([As.sub.2]O.sub.3) 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 (n=6 in each) were treated with normal saline (control), [As.sub.2]O.sub.3 [5 mg/(kg*day) intraperitoneally], leflunomide [5 mg/(kg*d) orally], or leflunomide [5 mg/(kg*d)+[As.sub.2]O.sub.3 [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.sub.2]O.sub.3 plus leflunomide compared with control rats or rats treated with either drug alone (P Conclusion Combination treatment with [As.sub.2]O.sub.3 and leflunomide protected hamster heart-xenografts in recipient rats. Author Affiliation: (1) Department of Urology, The First Affiliated Hospital of Harbin Medical University, 150000, Harbin, China (f) jiaozhixing@foxmail.com Article History: Registration Date: 07/27/2021 Accepted Date: 04/02/2020 Online Date: 07/28/2021 Byline: Teng-da Wang (1), Song-lin Xu (1), Zheng-yi Yu (1), Shao-bin Ni (1), Cheng Zhang (1), Zhi-xing Jiao (corresponding author) (1, f)

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Gale Document Number: GALE|A681422109