title: Promotion of oxidative stress in kidney of rats loaded with cystine dimethyl ester.
abstract: Cystinosis is a systemic genetic disease caused by a lysosomal transport deficiency accumulating cystine in most tissues. Although tissue damage might depend on cystine accumulation, the mechanisms of tissue damage are not fully understood. Studies performed in fibroblasts of cystinotic patients and in kidney cells loaded with cystine dimethyl ester (CDME) suggest that apoptosis is enhanced in this disease. Considering that oxidative stress is a known apoptosis inducer, our main objective was to investigate the effects of CDME loading on several parameters of oxidative stress in the kidney of young rats. Animals were injected twice a day with 1.6 micromol/g body weight CDME and/or 0.26 micromol/g body weight cysteamine (CSH) from the 16th to the 20th postpartum day and killed after 1 or 12 h. CDME induced lipoperoxidation and protein carbonylation and stimulated superoxide dismutase, glutathione peroxidase (GPx), and catalase activities, probably through the formation of superoxide anions, hydrogen peroxide, and hydroxyl free radicals. Coadministration of CSH, the drug used to treat cystinotic patients, prevented, at least in part, those effects, possibly acting as a scavenger of free radicals. These results suggest that the induction of oxidative stress might be one of the mechanisms leading to tissue damage in cystinotic patients.
authors.affiliation: Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade, Rua Ramiro Barcelos 2600, CEP 90.035-003, Porto Alegre, RS, Brazil.
authors.forename: Virgínia Cielo
authors.initials: VC
authors.lastname: Rech
authors.forename: Luciane Rosa
authors.initials: LR
authors.lastname: Feksa
authors.forename: Maria Fernanda
authors.initials: MF
authors.lastname: Arevalo do Amaral
authors.forename: Gustavo Waltereith
authors.initials: GW
authors.lastname: Koch
authors.forename: Moacir
authors.initials: M
authors.lastname: Wajner
authors.forename: Carlos Severo
authors.initials: CS
authors.lastname: Dutra-Filho
authors.forename: Angela
authors.initials: A
authors.lastname: Terezinha de Souza Wyse
authors.forename: Clovis Milton
authors.initials: CM
authors.lastname: Duval Wannmacher
mesh_terms: D000818:Animals; D002374:Catalase / Q000378:metabolism; D003543:Cysteamine / Q000008:administration & dosage / Q000494:pharmacology; D003553:Cystine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000633:toxicity; D003554:Cystinosis / Q000209:etiology* / Q000235:genetics / Q000473:pathology; D004347:Drug Interactions; D005452:Fluoresceins / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000378:metabolism; D007668:Kidney / Q000187:drug effects*; D015227:Lipid Peroxidation / Q000187:drug effects; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects*; D011506:Proteins / Q000032:analysis; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances / Q000032:analysis
chemical_list: D005452:Fluoresceins; D011506:Proteins; D017392:Thiobarbituric Acid Reactive Substances; D003553:Cystine; C037631:2',7'-dichlorofluorescein; D003543:Cysteamine; D006861:Hydrogen Peroxide; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; C034582:cystine dimethyl ester