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5-aminolaevulinic acid (ALA), enhances heme oxygenase (HO)-1 expression and attenuates tubulointerstitial fibrosis and renal apoptosis in chronic cyclosporine nephropathy.

Abstract：

BACKGROUND:Cyclosporine-A (CsA) is an immunosuppressant indicated for various immunological diseases; however, it can induce chronic kidney injury. Oxidative stress and apoptosis play a crucial role in CsA-induced nephrotoxicity. The present study evaluated the protective effect of combining 5-aminolaevulinic acid with iron (5-ALA/SFC), a precursor of heme synthesis, to enhance HO-1 activity against CsA-induced chronic nephrotoxicity. METHODS:Mice were divided into three groups: the control group (using olive oil as a vehicle), CsA-only group, and CsA+5-ALA/SFC group. After 28 days, the mice were sacrificed, and blood and kidney samples were collected. In addition to histological and biochemical examination, the mRNA expression of proinflammatory and profibrotic cytokines was assessed. RESULTS:Renal function in the 5-ALA/SFC treatment group as assessed by the serum creatinine and serum urea nitrogen levels was superior to that of the CsA-only treatment group, demonstrating that 5-ALA/SFC significantly attenuated CsA-induced kidney tissue inflammation, fibrosis, apoptosis, and tubular atrophy, as well as reducing the mRNA level of TNF-α, IL-6, TGF-β1, and iNOS while increasing HO-1. CONCLUSION:The activity of 5-ALA/SFC has important implications for clarifying the mechanism of HO-1 activity in CsA-induced nephrotoxicity and may provide a favorable basis for clinical therapy.

journal_name

Biochem Biophys Res Commun

journal_title

Biochemical and biophysical research communications

authors

Liu C,Zhu P,Fujino M,Isaka Y,Ito H,Takahashi K,Nakajima M,Tanaka T,Zhuang J,Li XK

doi

10.1016/j.bbrc.2018.11.175

subject

Has Abstract

pub_date

2019-01-08 00:00:00

pages

583-589

issue

2

eissn

0006-291X

issn

1090-2104

pii

S0006-291X(18)32610-X

journal_volume

508

pub_type

杂志文章

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