Pharmacological Activation of Nrf2 Pathway Improves Pancreatic Islet Isolation and Transplantation. Issue 11 (November 2015)

• Record Type: Journal Article
• Authors: Li, Shiri; Vaziri, Nosratola D.; Masuda, Yuichi; Hajighasemi-Ossareh, Mohammad; Robles, Lourdes; Le, Aimee; Vo, Kelly; Chan, Jefferson Y.; Foster, Clarence E.; Stamos, Michael J.; Ichii, Hirohito
• Is Part Of: Cell transplantation. Volume 24:Issue 11(2015)
• Page Start: 2273
• Page End: 2283
• Publication Date: 2015-11
• Subjects: Reactive oxygen species -- Oxidative stress -- Islet -- Isolation -- Transplantation -- Nuclear erythroid -- 2-related factor 2 (Nrf2); Cell transplantation -- Periodicals; Cell Transplantation; Cell transplantation; Electronic journals; Periodicals; Periodicals; 571.638
• DOI: 10.3727/096368915X686210
• Languages: English
• ISSNs: 0963-6897

Abstract

Oxidative stress is a major cause of islet damage and loss during the islet isolation process. The Nrf2 pathway plays a critical role in protecting the cells against oxidative stress. The aim of this study was to investigate the effect of an Nrf2 activator (dh404) on islet isolation and transplantation in a rodent model. Islet isolation was conducted using Nrf2-deficient and wild-type mice and vehicle-treated and Nrf2 activator (dh404)-treated rats. Islet yield, viability, and Nrf2 pathway activity were determined. An in vivo islet potency test was done. Islet yield and viability in Nrf2-deficient mice was significantly lower compared to wild-type ( p < 0.05) mice. Furthermore, administration of dh404 to normal Sprague–Dawley rats enhanced nuclear translocation of Nrf2 and elevated HO-1 expression in the pancreas. Islet yield and viability in dh404-treated rats was significantly higher compared to the vehicle-treated group ( p < 0.05). The diabetes cure rate in nude mice with chemically induced diabetes was significantly greater in those transplanted with islets from the dh404-treated group (6/9) than vehicle-treated rats (2/9, p < 0.05). The Nrf2 pathway plays a significant role in protecting islets against stress caused by the isolation process. Pharmacological activation of the Nrf2 pathway significantly increased HO-1 expression, improved islet yield, viability, and function after transplantation.