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FEBS Open Bio. 2019 Sep 8. doi: 10.1002/2211-5463.12729. [Epub ahead of print]

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

Author information

1
Division of Transplantation Immunology, National Research Institute for Child Health and Development, Tokyo, Japan.
2
AIDS Research Center, National Institute of Infectious Diseases, Tokyo, Japan.
3
Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.
4
Department of Nephrology, Osaka University Graduate School of Medicine, Osaka, Japan.
5
SBI Pharmaceuticals Co., Ltd, Tokyo, Japan.

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 HO-1, 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.

KEYWORDS:

5-aminolevulinic acid; Cyclosporine-A; apoptosis; heme oxygenase (HO)-1; oxidative stress

PMID:
31495071
DOI:
10.1002/2211-5463.12729
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