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Curcumin alleviates oxidative stress, inflammation, and renal fibrosis in remnant kidney through the N rf2–keap1 pathway
Author(s) -
Soetikno Vivian,
Sari Flori R.,
Lakshmanan Arun P.,
Arumugam Somasundaram,
Harima Meilei,
Suzuki Kenji,
Kawachi Hiroshi,
Watanabe Kenichi
Publication year - 2013
Publication title -
molecular nutrition and food research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.495
H-Index - 131
eISSN - 1613-4133
pISSN - 1613-4125
DOI - 10.1002/mnfr.201200540
Subject(s) - curcumin , oxidative stress , endocrinology , kidney , medicine , creatinine , inflammation , keap1 , fibrosis , blood urea nitrogen , kidney disease , chemistry , pharmacology , biochemistry , transcription factor , gene
Scope We hypothesized that curcumin, by increasing the expression of nuclear factor‐erythroid‐2‐related factor 2 (Nrf2), could reduce oxidative stress, inflammation, and renal fibrosis in remnant kidney. Methods and results Sprague‐Dawley rats were subjected to 5/6 nephrectomy and randomly assigned to untreated ( N x), curcumin‐treated (75 mg/kg/day, orally), and telmisartan‐treated groups (10 mg/kg/day, orally; as positive control). Sham‐operated rats also served as controls. Five/sixth nephrectomy caused renal dysfunction, as evidenced by elevated proteinuria, blood urea nitrogen, and plasma creatinine, and decreased creatinine clearance that were ameliorated by curcumin or telmisartan treatment. The N x rats demonstrated reduced N rf2 protein expression, whereas the Kelch‐like ECH‐associated protein 1 was upregulated and heme oxygenase‐1 level was significantly diminished. Consequently, N x animals had significantly higher kidney malondialdehyde concentration and lower glutathione peroxidase activity, which was associated with the upregulation of nicotinamide adenine dinucleotide phosphatase oxidase subunit (p67 phox and p22 phox ), NF ‐kappa B p65, TNF ‐α, TGF ‐β1, cyclooxygenase‐2, and fibronectin accumulation in remnant kidney. Interestingly, all of these changes were ameliorated by curcumin or telmisartan. Conclusion These findings demonstrate that, by modulating Nrf2‐Keap1 pathway, the curcumin effectively attenuates oxidative stress, inflammation, and renal fibrosis, which suggest that curcumin hold promising potential for safe treatment of chronic kidney disease.