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

BMC Nephrology

Ho Jun Chin²  Suhnggwon Kim²  Dong Wan Chae⁴  Ki Young Na⁴  Sejoong Kim⁴  Eun Seong Lee¹  Se Won Oh³ 

[1] Department of Internal Medicine, Seoul National University Bundang Hospital, Kyeong-Kido, Korea;Renal Institute, Seoul National University Medical Research Center, Seoul, Korea;Department of Internal Medicine, Eulji General Hospital, Eulji University College of Medicine, Seoul, Korea;Department of Internal Medicine, Seoul National University, Seoul, Korea

关键词: Renal injury;    Oxidative stress;    Cyclosporine;    Bilirubin;    Apoptosis;   

Others  :  1082934
DOI  :  10.1186/1471-2369-14-105

 received in 2012-03-18, accepted in 2013-04-24,  发布年份 2013

【 摘 要 】

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.

【 授权许可】

   
2013 Oh et al.; licensee BioMed Central Ltd.

【 图 表 】

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