Curcumin induces Nrf2 nuclear translocation and prevents glomerular hypertension, hyperfiltration, oxidant stress, and the decrease in antioxidant enzymes in 5/6 nephrectomized rats.
Renal injury resulting from renal ablation induced by 5/6 nephrectomy (5/6NX) is associated with oxidant stress, glomerular hypertension, hyperfiltration, and impaired Nrf2-Keap1 pathway. The purpose of this work was to know if the bifunctional antioxidant curcumin may induce nuclear translocation of Nrf2 and prevents 5/6NX-induced oxidant stress, renal injury, decrease in antioxidant enzymes, and glomerular hypertension and hyperfiltration. Four groups of rats were studied: (1) control, (2) 5/6NX, (3) 5/6NX +CUR, and (4) CUR (n = 8-10). Curcumin was given by gavage to NX5/6 +CUR and CUR groups (60 mg/kg/day) starting seven days before surgery. Rats were studied 30 days after NX5/6 or sham surgery. Curcumin attenuated 5/6NX-induced proteinuria, systemic and glomerular hypertension, hyperfiltration, glomerular sclerosis, interstitial fibrosis, interstitial inflammation, and increase in plasma creatinine and blood urea nitrogen. This protective effect was associated with enhanced nuclear translocation of Nrf2 and with prevention of 5/6NX-induced oxidant stress and decrease in the activity of antioxidant enzymes. It is concluded that the protective effect of curcumin against 5/6NX-induced glomerular and systemic hypertension, hyperfiltration, renal dysfunction, and renal injury was associated with the nuclear translocation of Nrf2 and the prevention of both oxidant stress and the decrease of antioxidant enzymes.
Renal Pathophysiology Laboratory, Department of Nephrology, Instituto Nacional de Cardiología Ignacio Chávez, 14080 Mexico City, DF, Mexico. ediliatapia@hotmail.com
Edilia
E
Tapia
Virgilia
V
Soto
Karla Mariana
KM
Ortiz-Vega
Guillermo
G
Zarco-Márquez
Eduardo
E
Molina-Jijón
Magdalena
M
Cristóbal-García
José
J
Santamaría
Wylly Ramsés
WR
García-Niño
Francisco
F
Correa
Cecilia
C
Zazueta
José
J
Pedraza-Chaverri
D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D001806:Blood Urea Nitrogen; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism*; D003404:Creatinine / Q000097:blood; D003474:Curcumin / Q000494:pharmacology*; D005919:Glomerular Filtration Rate / Q000187:drug effects*; D006973:Hypertension / Q000097:blood / Q000150:complications / Q000503:physiopathology / Q000517:prevention & control*; D007678:Kidney Glomerulus / Q000201:enzymology* / Q000503:physiopathology; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D009392:Nephrectomy; D016877:Oxidants / Q000633:toxicity; D018384:Oxidative Stress / Q000187:drug effects*; D010101:Oxygen Consumption / Q000187:drug effects; D021381:Protein Transport / Q000187:drug effects; D011507:Proteinuria / Q000097:blood / Q000150:complications / Q000503:physiopathology; D011677:Punctures; D051381:Rats; D017208:Rats, Wistar; D013599:Systole / Q000187:drug effects
D000975:Antioxidants; D051267:NF-E2-Related Factor 2; D016877:Oxidants; D003404:Creatinine; D003474:Curcumin