title: Chronic hyperhomocysteinemia induces oxidative damage in the rat lung.
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.
authors: 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.
authors: Aline A
authors: AA
authors: da Cunha
authors: Andréa G K
authors: AG
authors: Ferreira
authors: Maira J
authors: MJ
authors: da Cunha
authors: Carolina D
authors: CD
authors: Pederzolli
authors: Débora L
authors: DL
authors: Becker
authors: Juliana G
authors: JG
authors: Coelho
authors: Carlos S
authors: CS
authors: Dutra-Filho
authors: Angela T S
authors: AT
authors: Wyse
mesh_terms: D000818:Animals; D002374:Catalase / Q000378:metabolism; D002908:Chronic Disease; D005452:Fluoresceins / Q000378:metabolism; D005453:Fluorescence; D005978:Glutathione / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D006710:Homocysteine / Q000008:administration & dosage / Q000494:pharmacology; D020138:Hyperhomocysteinemia / Q000201:enzymology / Q000473:pathology*; D008168:Lung / Q000201:enzymology / Q000473:pathology*; D008954:Models, Biological; D009573:Nitrites / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
chemical_list: D005452:Fluoresceins; D009573:Nitrites; D017392:Thiobarbituric Acid Reactive Substances; D006710:Homocysteine; C037631:2',7'-dichlorofluorescein; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D005978:Glutathione