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

Se Won Oh, Eun Seong Lee, Sejoong Kim, Ki Young Na, Dong Wan Chae, Suhnggwon Kim, Ho Jun Chin

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29 Citations (Scopus)

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.

Original languageEnglish
Article number105
JournalBMC Nephrology
Volume14
Issue number1
DOIs
Publication statusPublished - 2013 May 21

Keywords

  • Apoptosis
  • Bilirubin
  • Cyclosporine
  • Oxidative stress
  • Renal injury

ASJC Scopus subject areas

  • Nephrology

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