Promotion of oxidative stress in kidney of rats loaded with cystine dimethyl ester.
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.
Rech
Virgínia Cielo
VC
Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade, Rua Ramiro Barcelos 2600, CEP 90.035-003, Porto Alegre, RS, Brazil.
Feksa
Luciane Rosa
LR
Arevalo do Amaral
Maria Fernanda
MF
Koch
Gustavo Waltereith
GW
Wajner
Moacir
M
Dutra-Filho
Carlos Severo
CS
Terezinha de Souza Wyse
Angela
A
Duval Wannmacher
Clovis Milton
CM
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
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