Effects of cysteamine on oxidative status in cerebral cortex of rats.
Cystinosis is a systemic genetic disease caused by a lysosomal transport deficiency accumulating cystine in most tissues. Tissue damage depends on cystine accumulation, but the mechanisms of this damage are still obscure. Cysteamine administration depletes cystine accumulated, increasing survive of affected patients. Studies performed in fibroblasts of cystinotic patients suggest that apoptosis is enhanced in this disease. Considering that oxidative stress is a known apoptosis inducer, our main objective was to investigate a possible antioxidant effect of cysteamine on several parameters of oxidative stress in the brain of young rats. Animals received three subcutaneous injections at 3-h intervals of a buffered solution (pH 7.4) of 10 mg/kg body weight cysteamine and were sacrificed 1 h after the last injection. Cysteamine decreased lipoperoxidation and glutathione peroxidase activity, and increased the carbonyl content of proteins and catalase activity. In vitro studies showed that cysteamine reduced lipoperoxidation, 2',7'-dihydrodichlorofluorescein oxidation, carbonyl content of proteins and catalase activity, and increased glutathione peroxidase activity. These results suggest that cysteamine may act as a scavenger of superoxide free radicals and hydrogen peroxide. Therefore, it is possible that cysteamine may extend life of cystinotic patients acting not only as a cystine depleting drug, but also as a free radical scavenger, reducing cell damage by apoptosis.
Kessler
Adriana
A
Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos 2600, CEP 90.035-003, Porto Alegre, Rio Grande do Sul, Brazil.
Biasibetti
Micheli
M
Feksa
Luciane Rosa
LR
Rech
Virginia Cielo
VC
Melo
Denizar Alberto da Silva
DA
Wajner
Moacir
M
Dutra-Filho
Carlos Severo
CS
Wyse
Angela Terezinha de Souza
AT
Wannmacher
Clovis Milton Duval
CM
D000818:Animals; D002374:Catalase / Q000378:metabolism; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D003543:Cysteamine / Q000494:pharmacology*; D005452:Fluoresceins; D005456:Fluorescent Dyes; D005979:Glutathione Peroxidase / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D050050:Protein Carbonylation / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
C109098:2,7-dihydrodichlorofluorescein diacetate; D005452:Fluoresceins; D005456:Fluorescent Dyes; D017392:Thiobarbituric Acid Reactive Substances; D003543:Cysteamine; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase