Pyruvate Metabolism in the Brain of Young Rats Intoxicated with Organic and Inorganic Lead

Abstract

The activities of lipoyl dehydrogenase, aspartate transaminase, and alanine transaminase, and levels of lactate were estimated in cerebral cortex, cerebellum, and brainstem of rats intoxicated acutely with tetraethyl lead and chronically with lead acetate. A significant inhibition of lipoyl dehydrogenase was observed in both groups of animals, whereas transaminase activities were increased in inorganic lead toxicity. Oxidative decarboxylation and anaplerosis of pyruvate was assessed in brain slices using [1-14C]pyruvate. Pyruvate dehydrogenase activity was decreased in both organic and inorganic lead toxicity, whereas labelling of aspartate and alanine was increased in inorganic lead toxicity. In studies in vitro, lead acetate showed a more significant effect than tetraethyl lead. The higher anaerobic metabolism in inorganic lead toxicity, as evidenced by increased anaerobic lactate production by brain slices, could either be an adaptive mechanism or be due to the delayed maturation of brain in the developing rat. Such a mechanism does not occur in acute organic lead toxicity, as the compound brings about massive and rapid degenerative changes in brain, resulting in convulsive seizures and death of the animals.

Protective Effect of Volatile Oil, Alcoholic and Aqueous Extracts ofOriganum majoranaon Lead Acetate Toxicity in Mice

“…Lead induced a significant genotoxic effect indicated by increased rate of micronucleus and chromosomal aberrations. Many studies have demonstrated similar results, that lead changes the liver functions inducing liver fattening and increased AST, ALT, ALP, lactate dehydrogenase enzymes and decreased albumin/globulin ratio and changed serum lipid values (Mikhail et al 1980;Regunathan & Sundaresan 1984;Othman & El Missiry 1998;Todorovic & Vujanovic 2002;Sivaprasad et al 2003).…”

Alteration in Carbohydrate Metabolism by Sub-Acute Lead Exposure: A Dose-Dependent Study

“…This is supported by the present study where lead exposure at the present dose and duration causes suppressed the activity of PDH in the liver. LA induced inhibition of PDH activity was also observed in a rat model [36]. Inhibition of PDH activity may be due to the selective affinity of divalent cation as like lead towards the sulphydryl groups of the enzyme [23].…”

Chloride‐Dependent Uncoupling of Oxidative Phosphorylation by Triethyllead and Triethyltin Increases Cytosolic Free Calcium in Guinea Pig Cerebral Cortical Synaptosomes

“…TEL causes irreversible neuronal death in some areas of the brain (see Seawright et al, 1984), an effect thought to be mediated by an excitotoxic mechanism (see Cremer, 1984). It has been found to be an inhibitor of pyruvate metabolism in the cortex of the rat brain both in vivo and in vitro (Regunathan and Sundaresan, 1984). TEL has been reported to prevent the y-aminobutyric acid reuptake mechanism of synaptosomes independently of energy levels and of external C1- (Seidman and Verity, 1987).…”

“…In isolated mitochondria, TEL and TET have been shown to prevent pyruvate transport independently of the energy state of mitochondria (Skilleter, 1975). On the other hand, TEL has been shown to be an inhibitor of pyruvate decarboxylation in the rat cortex (Regunathan and Sundaresan, 1984). TEL stimulates synaptosomal glycolysis more extensively than respiration, suggesting that glycolytic substrates are available for mitochondria (Kauppinen and Komulainen, unpublished observations).…”