5-ALA/SFC enhances HO-1 expression through the MAPK/Nrf2 antioxidant pathway and attenuates murine tubular epithelial cell apoptosis

5-ALA/SFC 通过 MAPK/Nrf2 抗氧化途径增强 HO-1 表达并减弱小鼠肾小管上皮细胞凋亡

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作者:Chi Liu, Masayuki Fujino, Shuoji Zhu, Yoshitaka Isaka, Hidenori Ito, Kiwamu Takahashi, Motowo Nakajima, Tohru Tanaka, Ping Zhu, Xiao-Kang Li

Abstract

Cyclosporin A (CsA) is a common immunosuppressant, but its use is limited as it can cause chronic kidney injury. Oxidative stress and apoptosis play a key role in CsA-induced nephrotoxicity. This study investigated the protective effect of 5-aminolevulinic acid and iron (5-ALA/SFC) on CsA-induced injury in murine proximal tubular epithelial cells (mProx24). 5-ALA/SFC significantly inhibited apoptosis in CsA-treated mProx24 cells with increases in heme oxygenase (HO)-1, nuclear factor E2-related factor 2 (Nrf2), and p38, and Erk-1/2 phosphorylation. Moreover, 5-ALA/SFC suppressed production of reactive oxygen species in CsA-exposed cells and inhibition of HO-1 suppressed the protective effects of 5-ALA/SFC. In summary, 5-ALA/SFC may have potential for development into a treatment for the anti-nephrotoxic/apoptotic effects of CsA.

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