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Chronic hyperhomocysteinemia induces oxidative damage in the rat lung

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Abstract

Tissue accumulation of homocysteine occurs in classical homocystinuria, a metabolic disease characterized biochemically by cystathionine β-synthase deficiency. Vascular manifestations such as myocardial infarction, cerebral thrombosis, hepatic steatosis, and pulmonary embolism are common in this disease and poorly understood. In this study, we investigated the effect of chronic hyperhomocysteinemia on some parameters of oxidative stress (thiobarbituric acid-reactive substances, protein carbonyl content, 2′,7′-dichlorofluorescein fluorescence assay, and total radical-trapping antioxidant potent) and activities of antioxidant enzymes (superoxide dismutase, catalase, and glutathione peroxidase) in the rat lung. Reduced glutathione content and glucose 6-phosphate dehydrogenase activity, as well as nitrite levels, were also evaluated. Wistar rats received daily subcutaneous injections of Hcy (0.3–0.6 μmol/g body weight) from the 6th to the 28th days-of-age and the control group received saline. One and 12 h after the last injection, rats were killed and the lungs collected. Hyperhomocysteinemia increased lipid peroxidation and oxidative damage to protein, and disrupted antioxidant defenses (enzymatic and non-enzymatic) in the lung of rats, characterizing a reliable oxidative stress. In contrast, this amino acid did not alter nitrite levels. Our findings showed a consistent profile of oxidative stress in the lung of rats, elicited by homocysteine, which could explain, at least in part, the mechanisms involved in the lung damage that is present in some homocystinuric patients.

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Acknowledgments

This work was supported in part by grants from Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq, Brazil) and Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul (FAPERGS, RS, Brazil).

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  1. Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600-Anexo, Porto Alegre, RS, CEP 90035-003, Brazil

    Aline A. da Cunha, Andréa G. K. Ferreira, Maira J. da Cunha, Carolina D. Pederzolli, Débora L. Becker, Juliana G. Coelho, Carlos S. Dutra-Filho & Angela T. S. Wyse

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  1. Aline A. da Cunha
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  2. Andréa G. K. Ferreira
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  3. Maira J. da Cunha
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  4. Carolina D. Pederzolli
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Correspondence to Angela T. S. Wyse.

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da Cunha, A.A., Ferreira, A.G.K., da Cunha, M.J. et al. Chronic hyperhomocysteinemia induces oxidative damage in the rat lung. Mol Cell Biochem 358, 153–160 (2011). https://doi.org/10.1007/s11010-011-0930-2

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