RESUMEN
The effect of age and peroxidative stress on the concentration of a deoxyguanosine malondialdehyde adduct (dG-MDA) in rat tissues was investigated. Vitamin E deficiency had no effect on the dG-MDA content of liver DNA in rats fed a diet containing 10% corn oil. When 2% cod liver oil was added to this diet, the dG-MDA content of liver DNA doubled in the positive controls fed a high level of vitamin E (100 ppm dl-alpha-tocopherol), and there was a further increase when vitamin E was deleted. Neither iron nitrilotriacetate administration nor choline deficiency had any effect on the dG-MDA content of liver DNA. Carbon tetrachloride had a lowering effect. The failure of iron or carbon tetrachloride administration and of vitamin E deficiency to increase liver dG-MDA is consistent with their failure in previous experiments to affect the urinary excretion of dG-MDA. In contrast, these forms of peroxidative stress produce large increments in the urinary excretion of MDA adducts with lysine, reflecting increased formation and degradation of MDA-modified proteins. DNA appears to be protected from modification by MDA produced at extranuclear sites. The frequency of dG-MDA in different tissues of 4-month-old rats varied markedly: brain >> liver > kidneys and testes. Higher concentrations of dG-MDA were found in the liver and kidneys, but not the testes, of 25-month-old rats. The determinants of the concentration of dG-MDA in DNA merit further investigation.
Asunto(s)
Envejecimiento , Aductos de ADN/análisis , Desoxiguanosina/análisis , Malondialdehído/análisis , Estrés Oxidativo , Animales , Química Encefálica , Tetracloruro de Carbono/farmacología , Aceite de Hígado de Bacalao/administración & dosificación , Aceite de Maíz/administración & dosificación , ADN/análisis , ADN/metabolismo , Desoxiguanosina/metabolismo , Grasas Insaturadas en la Dieta/administración & dosificación , Riñón/química , Hígado/química , Hígado/efectos de los fármacos , Masculino , Malondialdehído/metabolismo , Ratas , Testículo/química , Vitamina E/administración & dosificación , Deficiencia de Vitamina E/metabolismoRESUMEN
In an ongoing study, rat and human urine have been examined for the presence of malondialdehyde (MDA) derivatives as indicators of the nature of lipid peroxidative damage caused by this compound in vivo. MDA in urine was found to be present mainly in the form of two lysine adducts, one acetylated and the other unacetylated, reflecting in vivo reactions with tissue proteins. Two minor metabolites were identified as adducts with the phospholipid bases serine and ethanolamine and a third one as an adduct with the nucleic acid base guanine. The identification of an MDA adduct with deoxyguanosine (dG-MDA) among the products of hydrolysis of rat liver DNA suggested the possible occurrence of this compound in urine. In the present study dG-MDA was identified in rat and in human urine, and a high-performance liquid chromatographic method utilizing fluorescence detection was developed for its estimation. The method is sensitive to 1 pmol of dG-MDA and requires a minimum of 1 mL of rat urine or 5 mL of human urine. Its rate of excretion by five-week-old rats (28.54 +/- 2.28 nmol/kg/24 h) (mean +/- SEM) was higher than that for nine-week-old rats (6.29 +/- 1.02) and much higher than that for adult humans (0.40 +/- 0.05). The results indicate that, as reported for 8-hydroxy-deoxyguanosine, dG-MDA excretion is related to metabolic rate. Excretion of dG-MDA by the rat, like the excretion of total MDA, declines during growth on a body weight basis at a rate similar to the decrease in resting energy metabolism.(ABSTRACT TRUNCATED AT 250 WORDS)