Early effects of inorganic lead on immature rat brain mitochondrial respiration.

摘要: Extract: Inorganic lead, added to the diet of suckling rat in high doses, produces an encephalopathy similar that seen immature human. Pathologic changes edema and hemorrhage are earliest most prominent cerebellum. In this study, we measured respiration cerebral hemisphere cerebellar mitochondria isolated from led-fed age-matched normal pups. Lactating mothers were begun on ad libitum feedings containing 4% lead carbonate when their pups 2 weeks old. Mitchondria by differential centrifugation. Oxygen consumption was polarographically. NAD-linked with oxidation substrate pair, glutamate malate. Cytochrome oxidase (cytochrome c oxidase, EC. 1.9.3.1) activity presence tetramethyl-p-phenylenediamine dihydrochloride (TMPD) ascorbate. Within days starting feedings, showed a significant loss body weight (P < 0.02) and, after 1 week, wet 0.01) compared controls. Overt appeared two nine litters receiving for week half feedings. None lead-fed developed encephalopathic signs. With there progressive decrease, relative controls, ADP/O ratios both mitochrondria animals. After these differences regions (cerebellum, P<0.02; cerebrum, P<0.005). Respiratory control significantly lower rats within beginning (P<0.02) P<0.01; P<0.05). The decrease animals or less due small state 3 large, but inconsistent, increase 4 respiration. marked inhibition respiration, controls hemisphere, P<0.05).In animals, cytochrome controls: highly 0.001) Speculation: effects inorganic greater mitochon- dria cerebellum than hemispheres. respiratory chain function, which sooner any previously reported biochemical morpho- logic effect cerebellum, may constitute early step pathogenesis is predominant region brain. mitochondria, be acting as uncoupling agent, such dinitrophenol, affecting cyto- chrome activity. maturing brain sensitive at critical period rapid synthesis increasing enzymes. related regional properties during maturational period.