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Bilirubin attenuates the renal tubular injury by inhibition of oxidative stress and apoptosis

Authors
Oh S.W.Lee E.S.Kim S.Na K.Y.Chae D.W.Kim S.Chin H.J.
Issue Date
2013
Keywords
Apoptosis; Bilirubin; Cyclosporine; Oxidative stress; Renal injury
Citation
BMC Nephrology, v.14, no.1
Indexed
SCIE
SCOPUS
Journal Title
BMC Nephrology
Volume
14
Number
1
URI
https://scholarworks.korea.ac.kr/kumedicine/handle/2020.sw.kumedicine/11382
DOI
10.1186/1471-2369-14-105
ISSN
1471-2369
Abstract
Background: Bilirubin (BIL) has been recognized as an endogenous antioxidant that shows a protective effect for cardiorenal diseases. We investigated whether administration of BIL had a protective effect on cyclosporine (CsA)-induced nephropathy (CIN), and examined the effects of BIL on the oxidative stress and apoptosis. Methods. BIL was pretreated intraperitoneally three times for a week (60 mg/kg), and CsA was injected for 4 weeks (15 mg/kg/day, subcutaneous). Proximal tubular epithelial (HK2) cells were pretreated with 0.1mg/ml of BIL for 24 hours, and then treated with 20 μM of CsA for another 24 hours. Results: CsA induced marked increases in urine kidney injury molecule-1 (Kim-1) and neutrophil gelatinase-associated lipocalin (NGAL) concentrations (P < 0.05). BIL reduced urine Kim-1 in CIN (P < 0.05), while urine NGAL exhibited a decreasing tendency. In CsA-treated rat kidneys, the protein expression of NOX4 and p22phox was reduced by BIL (P < 0.05). BIL ameliorated CsA-induced arteriolopathy, tubulointerstitial fibrosis, tubular injury, and the apoptosis examined by TUNEL assay (P < 0.01). In HK2 cells, BIL reduced intracellular reactive oxygen species in CsA-treated cells. CsA increased the protein expression of bax, cleaved caspase-9, caspase-3 and the activity of caspase-3; however, the anti-apoptotic bcl-2 protein was reduced. These changes were recovered by BIL (P < 0.05). Conclusions: The direct administration of BIL protected against CsA-induced tubular injury via inhibition of oxidative stress and apoptosis. © 2013 Oh et al.; licensee BioMed Central Ltd.
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Oh, Se Won
Anam Hospital (Department of Nephrology and Hypertension, Anam Hospital)
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