title: Mycophenolate mofetil and curcumin provide comparable therapeutic benefit in experimental chronic kidney disease: role of Nrf2-Keap1 and renal dopamine pathways.
abstract: Increased oxidative stress and inflammation have an important role in the pathophysiology of chronic kidney disease (CKD). On the other hand, more affordable therapeutic alternatives for treating this disease are urgently needed. Therefore, we compared the therapeutic efficacy of curcumin and mycophenolate mofetil (MMF) in 5/6 nephrectomy (5/6 Nx) model of CKD. Also, we evaluated whether both compounds provide benefit through the preservation of similar antioxidant mechanisms. Four groups of male Wistar were studied over a period of 4 wk. Control sham group (n= 12), 5/6 Nx (n = 12), 5/6 Nx + MMF (30 mg/k BW/day, n = 11) and 5/6 Nx + Curcumin (120 mg/k BW/day, n = 12). Renal function and markers of oxidative stress and inflammation were evaluated. Also Nrf2-Keap1 and renal dopamine, antioxidant pathways were assessed. 5/6 Nx induced an altered renal autoregulation response, proteinuria, and hypertension; these effects were in association with increased oxidative stress, endothelial dysfunction and renal inflammation. The mechanisms associated with these alterations included a reduced nuclear translocation of Nrf2 and hyperphosphorylation of dopamine D1 receptor with a concurrent overactivation of renal NADPH oxidase. Treatments with MMF and curcumin provided equivalent therapeutic efficacy as both prevented functional renal alterations as well as preserved antioxidant capacity and avoided renal inflammatory infiltration. Moreover, both treatments preserved Nrf2-Keap1 and renal dopamine antioxidant pathways. In summary, therapeutic strategies aimed to preserve renal antioxidant pathways can help to retard the progression of CKD.
authors.affiliation: a Laboratory of Renal Physiopathology , INC Ignacio Chávez , Mexico City , Mexico ;|b Department of Nephrology , INC Ignacio Chávez , Mexico City , Mexico ;
authors.forename: Edilia
authors.initials: E
authors.lastname: Tapia
authors.affiliation: a Laboratory of Renal Physiopathology , INC Ignacio Chávez , Mexico City , Mexico ;|b Department of Nephrology , INC Ignacio Chávez , Mexico City , Mexico ;
authors.forename: Fernando
authors.initials: F
authors.lastname: García-Arroyo
authors.affiliation: a Laboratory of Renal Physiopathology , INC Ignacio Chávez , Mexico City , Mexico ;|b Department of Nephrology , INC Ignacio Chávez , Mexico City , Mexico ;
authors.forename: Octaviano
authors.initials: O
authors.lastname: Silverio
authors.affiliation: a Laboratory of Renal Physiopathology , INC Ignacio Chávez , Mexico City , Mexico ;|b Department of Nephrology , INC Ignacio Chávez , Mexico City , Mexico ;
authors.forename: Alma N
authors.initials: AN
authors.lastname: Rodríguez-Alcocer
authors.affiliation: a Laboratory of Renal Physiopathology , INC Ignacio Chávez , Mexico City , Mexico ;|b Department of Nephrology , INC Ignacio Chávez , Mexico City , Mexico ;
authors.forename: Ana B
authors.initials: AB
authors.lastname: Jiménez-Flores
authors.affiliation: a Laboratory of Renal Physiopathology , INC Ignacio Chávez , Mexico City , Mexico ;|b Department of Nephrology , INC Ignacio Chávez , Mexico City , Mexico ;
authors.forename: Magdalena
authors.initials: M
authors.lastname: Cristobal
authors.affiliation: a Laboratory of Renal Physiopathology , INC Ignacio Chávez , Mexico City , Mexico ;|b Department of Nephrology , INC Ignacio Chávez , Mexico City , Mexico ;
authors.forename: Abraham S
authors.initials: AS
authors.lastname: Arellano
authors.affiliation: c Department of Pathology , INC Ignacio Chávez , Mexico City , Mexico ;
authors.forename: Virgilia
authors.initials: V
authors.lastname: Soto
authors.affiliation: a Laboratory of Renal Physiopathology , INC Ignacio Chávez , Mexico City , Mexico ;|b Department of Nephrology , INC Ignacio Chávez , Mexico City , Mexico ;
authors.forename: Horacio
authors.initials: H
authors.lastname: Osorio-Alonso
authors.affiliation: d Department of Biology, Faculty of Chemistry , UNAM , Mexico City , Mexico.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Molina-Jijón
authors.affiliation: d Department of Biology, Faculty of Chemistry , UNAM , Mexico City , Mexico.
authors.forename: José
authors.initials: J
authors.lastname: Pedraza-Chaverri
authors.affiliation: a Laboratory of Renal Physiopathology , INC Ignacio Chávez , Mexico City , Mexico ;|b Department of Nephrology , INC Ignacio Chávez , Mexico City , Mexico ;
authors.forename: Laura G
authors.initials: LG
authors.lastname: Sanchez-Lozada
mesh_terms: D000818:Animals; D003474:Curcumin / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism*; D000072019:Kelch-Like ECH-Associated Protein 1 / Q000378:metabolism*; D008297:Male; D009173:Mycophenolic Acid / Q000494:pharmacology*; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D051436:Renal Insufficiency, Chronic / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology
chemical_list: C486610:KEAP1 protein, rat; D000072019:Kelch-Like ECH-Associated Protein 1; D051267:NF-E2-Related Factor 2; C495637:Nfe2l2 protein, rat; D009173:Mycophenolic Acid; D003474:Curcumin; D004298:Dopamine
keywords: D1R receptor; NADPH oxidase; endothelial dysfunction