Curcumin alleviates oxidative stress, inflammation, and renal fibrosis in remnant kidney through the Nrf2–keap1 pathway
Article first published online: 23 NOV 2012
© 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Molecular Nutrition & Food Research
Special Issue: Curcumin: Recent Insights, Novel Developments, New Challenges
Volume 57, Issue 9, pages 1649–1659, September 2013
How to Cite
Soetikno, V., Sari, F. R., Lakshmanan, A. P., Arumugam, S., Harima, M., Suzuki, K., Kawachi, H. and Watanabe, K. (2013), Curcumin alleviates oxidative stress, inflammation, and renal fibrosis in remnant kidney through the Nrf2–keap1 pathway. Mol. Nutr. Food Res., 57: 1649–1659. doi: 10.1002/mnfr.201200540
- Issue published online: 2 SEP 2013
- Article first published online: 23 NOV 2012
- Manuscript Accepted: 19 SEP 2012
- Manuscript Revised: 18 SEP 2012
- Manuscript Received: 13 AUG 2012
- Yujin Memorial Grant, Ministry of Education, Culture, Sports and Technology of Japan
- Promotion and Mutual Aid Corporation for Private Schools
- Chronic kidney disease;
- Oxidative stress
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 (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-α, TGF-β1, cyclooxygenase-2, and fibronectin accumulation in remnant kidney. Interestingly, all of these changes were ameliorated by curcumin or telmisartan.
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.