Curcumin alleviates oxidative stress, inflammation, and renal fibrosis in remnant kidney through the Nrf2-keap1 pathway

Vivian Soetikno, Flori R. Sari, Arun Lakshmanan, Somasundaram Arumugam, Meilei Harima, Kenji Suzuki, Hiroshi Kawachi, Kenichi Watanabe

Research output: Contribution to journalArticle

107 Citations (Scopus)

Abstract

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 (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. 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.

Original languageEnglish
Pages (from-to)1649-1659
Number of pages11
JournalMolecular Nutrition and Food Research
Volume57
Issue number9
DOIs
Publication statusPublished - 1 Sep 2013
Externally publishedYes

Fingerprint

Curcumin
curcumin
fibrosis
Oxidative Stress
Fibrosis
oxidative stress
inflammation
kidneys
Inflammation
Kidney
Nephrectomy
creatinine
heme oxygenase (biliverdin-producing)
Creatinine
rats
Ureaplasma
transcription factor NF-kappa B
Heme Oxygenase-1
NF-kappa B
NAD (coenzyme)

Keywords

  • Chronic kidney disease
  • Curcumin
  • Fibrosis
  • Inflammation
  • Oxidative stress

ASJC Scopus subject areas

  • Food Science
  • Biotechnology

Cite this

Curcumin alleviates oxidative stress, inflammation, and renal fibrosis in remnant kidney through the Nrf2-keap1 pathway. / Soetikno, Vivian; Sari, Flori R.; Lakshmanan, Arun; Arumugam, Somasundaram; Harima, Meilei; Suzuki, Kenji; Kawachi, Hiroshi; Watanabe, Kenichi.

In: Molecular Nutrition and Food Research, Vol. 57, No. 9, 01.09.2013, p. 1649-1659.

Research output: Contribution to journalArticle

Soetikno, Vivian ; Sari, Flori R. ; Lakshmanan, Arun ; Arumugam, Somasundaram ; Harima, Meilei ; Suzuki, Kenji ; Kawachi, Hiroshi ; Watanabe, Kenichi. / Curcumin alleviates oxidative stress, inflammation, and renal fibrosis in remnant kidney through the Nrf2-keap1 pathway. In: Molecular Nutrition and Food Research. 2013 ; Vol. 57, No. 9. pp. 1649-1659.
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AU - Soetikno, Vivian

AU - Sari, Flori R.

AU - Lakshmanan, Arun

AU - Arumugam, Somasundaram

AU - Harima, Meilei

AU - Suzuki, Kenji

AU - Kawachi, Hiroshi

AU - Watanabe, Kenichi

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N2 - 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 (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. 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.

AB - 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 (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. 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.

KW - Chronic kidney disease

KW - Curcumin

KW - Fibrosis

KW - Inflammation

KW - Oxidative stress

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