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Title: Curcumin alleviates oxidative stress, inflammation, and renal fibrosis in remnant kidney through the Nrf2–keap1 pathway
Authors: Vivian Soetikno
Flori Ratna Sari
Arun P. Lakshmanan
Somasundaram Arumugam
Meilei Harima
Kenji Suzuki
Hiroshi Kawachi
Kenichi Watanabe
Advisors: Kenichi Watanabe
Keywords: Chronic kidney disease;Curcumin;Fibrosis;Inflammation;Oxidative stress
Issue Date: 2013
Publisher: Wiley-VCH VerlagGmbH& Co
Abstract: Scope: We hypothesized that curcumin, by increasing the expression of nuclear factorerythroid-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 (Nx), 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 Nx rats demonstrated reduced Nrf2 protein expression, whereas the Kelch-like ECH-associated protein 1 was upregulated and heme oxygenase-1 level was significantly diminished. Consequently, Nx 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 (p67phox and p22phox), NF-kappaB p65, TNF- , TGF- 1, 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.
ISSN: 1613-4133
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