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Promotion of oxidative stress in kidney of rats loaded with cystine dimethyl ester

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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 μmol/g body weight CDME and/or 0.26 μmol/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.

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Acknowledgements

This work was supported in part by grants from Conselho Nacional de Desenvolvimento Científico e tecnológico (CNPq-Brazil), Fundação de Amparo à Pesquisa do Rio Grande do Sul (FAPERGS, RS-Brazil) and Programa de Núcleos de Excelência (PRONEX-CNPq /FAPERGS-Brazil).

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  1. Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade, Rua Ramiro Barcelos 2600, CEP 90.035-003, Porto Alegre, RS, Brazil

    Virgínia Cielo Rech, Luciane Rosa Feksa, Maria Fernanda Arevalo do Amaral, Gustavo Waltereith Koch, Moacir Wajner, Carlos Severo Dutra-Filho, Angela Terezinha de Souza Wyse & Clovis Milton Duval Wannmacher

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  1. Virgínia Cielo Rech
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  2. Luciane Rosa Feksa
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Correspondence to Clovis Milton Duval Wannmacher.

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Rech, V.C., Feksa, L.R., Arevalo do Amaral, M.F. et al. Promotion of oxidative stress in kidney of rats loaded with cystine dimethyl ester. Pediatr Nephrol 22, 1121–1128 (2007). https://doi.org/10.1007/s00467-007-0494-2

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