title: Lipoic acid does not improve renal function markers in 5/6 nephrectomy model: possible role of Nrf2 inactivation.
abstract: Chronic kidney disease (CKD) progression and complications are associated with increased oxidative stress, as well as with Nrf2 inactivation. Lipoic acid (LA) has been considered an inducer of Nrf2 antioxidant response. We tested whether oral administration of LA provides beneficial effects in experimental CKD in rats. Wistar rats underwent 5/6 nephrectomy (CKD group) or sham laparotomy. Seven days later, CKD group was divided into three subgroups that received: (i) LA continuously in the drinking water (100 mg/kg/day), (ii) LA by gavage every other day (100 mg/kg), or (iii) no LA treatment. LA treatment lasted until day 60. Plasma urea and creatinine, 24 h-proteinuria, glomerulosclerosis, interstitial fibrosis/tubular atrophy, and Nrf2 activation were analyzed. All parameters measured were significantly altered in the untreated CKD group, compared with the sham group, as expected. Oral LA administration, either in the drinking water or by gavage, did not improve significantly any parameter, comparing the treated-groups with the untreated CKD group. These results indicate that oral LA administration for 53 days was ineffective to reactivate Nrf2 in the remnant kidney of uremic rats, likely preventing improvements in biochemical and histopathological markers of renal function.
authors.affiliation: a Departamento de Patologia Básica , Universidade Federal do Paraná, Centro Politécnico , Curitiba , Brazil ;
authors.forename: Sze M
authors.initials: SM
authors.lastname: Lo
authors.affiliation: a Departamento de Patologia Básica , Universidade Federal do Paraná, Centro Politécnico , Curitiba , Brazil ;
authors.forename: Fernando T
authors.initials: FT
authors.lastname: Dal Lin
authors.affiliation: b Departamento de Patologia Médica , Setor de Ciências da Saúde, Universidade Federal do Paraná , Curitiba , Brazil ;
authors.forename: Maria F
authors.initials: MF
authors.lastname: Soares
authors.affiliation: c Departamento de Análises Clínicas , Setor Ciências da Saúde, Universidade Federal do Paraná , Curitiba , Brazil ;
authors.forename: Aline B
authors.initials: AB
authors.lastname: Hauser
authors.affiliation: d School of Medicine , Pontifícia Universidade Católica do Paraná , Curitiba , Brazil.
authors.forename: Roberto
authors.initials: R
authors.lastname: Pecoits-Filho
authors.affiliation: a Departamento de Patologia Básica , Universidade Federal do Paraná, Centro Politécnico , Curitiba , Brazil ;
authors.forename: Lia S
authors.initials: LS
authors.lastname: Nakao
mesh_terms: D000818:Animals; D008297:Male; D051381:Rats; D004195:Disease Models, Animal; D007668:Kidney / Q000187:drug effects / Q000502:physiology; D009392:Nephrectomy / Q000379:methods; D017208:Rats, Wistar; D051436:Renal Insufficiency, Chronic / Q000188:drug therapy; D008063:Thioctic Acid / Q000494:pharmacology / Q000627:therapeutic use; D051267:NF-E2-Related Factor 2 / Q000502:physiology
chemical_list: D008063:Thioctic Acid; D051267:NF-E2-Related Factor 2; C495637:Nfe2l2 protein, rat
keywords: 5/6 Nephrectomy; Nrf2; antioxidant therapy; chronic kidney disease; lipoic acid