title: Curcumin alleviates oxidative stress, inflammation, and renal fibrosis in remnant kidney through the Nrf2-keap1 pathway.
abstract: METHODS
  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.
  
  
  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 (p67(phox) and p22(phox) ), 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Clinical Pharmacology, Faculty of Pharmaceutical Sciences, Niigata University of Pharmacy and Applied Life Sciences, Niigata City, Japan.
authors.forename: Vivian
authors.initials: V
authors.lastname: Soetikno
authors.forename: Flori R
authors.initials: FR
authors.lastname: Sari
authors.forename: Arun P
authors.initials: AP
authors.lastname: Lakshmanan
authors.forename: Somasundaram
authors.initials: S
authors.lastname: Arumugam
authors.forename: Meilei
authors.initials: M
authors.lastname: Harima
authors.forename: Kenji
authors.initials: K
authors.lastname: Suzuki
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kawachi
authors.forename: Kenichi
authors.initials: K
authors.lastname: Watanabe
mesh_terms: D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology; D001565:Benzoates / Q000494:pharmacology; D001794:Blood Pressure; D001806:Blood Urea Nitrogen; D003404:Creatinine / Q000097:blood; D003474:Curcumin / Q000494:pharmacology*; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D005353:Fibronectins / Q000235:genetics / Q000378:metabolism; D005355:Fibrosis; D006419:Heme Oxygenase (Decyclizing) / Q000235:genetics / Q000378:metabolism; D007249:Inflammation / Q000188:drug therapy*; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D000072019:Kelch-Like ECH-Associated Protein 1; D007668:Kidney / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D007674:Kidney Diseases / Q000188:drug therapy*; D008297:Male; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000378:metabolism*; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D009392:Nephrectomy; D018384:Oxidative Stress / Q000187:drug effects*; D011507:Proteinuria / Q000188:drug therapy; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D000077333:Telmisartan; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
chemical_list: D001562:Benzimidazoles; D001565:Benzoates; D005353:Fibronectins; D047908:Intracellular Signaling Peptides and Proteins; C486610:KEAP1 protein, rat; D000072019:Kelch-Like ECH-Associated Protein 1; D051267:NF-E2-Related Factor 2; D016328:NF-kappa B; C495637:Nfe2l2 protein, rat; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha; D003404:Creatinine; D006419:Heme Oxygenase (Decyclizing); C491523:Hmox1 protein, rat; D051546:Cyclooxygenase 2; C489691:Ptgs2 protein, rat; D003474:Curcumin; D000077333:Telmisartan