Impairment of energy metabolism in hippocampus of rats subjected to chemically-induced hyperhomocysteinemia

AbstractHomocystinuria is an inherited metabolic disease biochemically characterized by tissue accumulation of homocysteine (Hcy). Mental retardation, ischemia and other neurological features, whose mechanisms are still obscure are common symptoms in homocystinuric patients. In this work, we investigated the effect of Hcy administration in Wistar rats on some parameters of energy metabolism in the hippocampus, a cerebral structure directly involved with cognition. The parameters utilized were 14CO2 production, glucose uptake, lactate release and the activities of succinate dehydrogenase and cytochrome c oxidase (COX). Chronic hyperhomocysteinemia was induced by subcutaneous administration of Hcy twice a day from the 6th to the 28th day of life in doses previously determined in our laboratory. Control rats received saline in the same volumes. Rats were killed 12 h after the last injection. Results showed that Hcy administration significantly diminished 14CO2 production and glucose uptake, as well as succinate dehydrogenase and COX activities. It is suggested that impairment of brain energy metabolism may be related to the neurological symptoms present in homocystinuric patients

Fenilcetonúria experimental : atividade da piruvatoquinase (PK) em córtex cerebral de ratos jovens

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β-Cyclodextrins alter the energy metabolism-related enzyme activities in rats

Abstract Although widely used in medicine, separation technology, and other fields, the effects of cyclodextrins on the activities of phosphoryl transfer enzymes have not been previously evaluated. In vivo studies evaluated the function of cyclodextrins as active compounds. Despite the use of cyclodextrins as active compounds, the effects of cyclodextrins on hepatic and renal tissues remain to be fully elucidated. The primary objective of this study was to evaluate the effects of β- cyclodextrins, methyl-β-cyclodextrin (M-β- cyclodextrins), and (2-hydroxypropyl)-β-cyclodextrin (HP-β-cyclodextrins) on enzyme activities regulating the maintenance of energy homeostasis in the kidney and liver tissues in relation to toxicity. Serum levels of liver and kidney markers were measured, and oxidative stress parameters were assessed. After 60-day treatments, we observed that the administration of β-cyclodextrins and M-β-cyclodextrins inhibited the hepatic activity of pyruvate kinase, an irreversible enzyme within the glycolytic pathway. Additionally, administration of HP-β-cyclodextrins inhibited creatine kinase activity and increased the total sulfhydryl content in kidneys. Here, we demonstrated for the first time that β-cyclodextrins, M-β-cyclodextrins, and HP-β-cyclodextrins cause bioenergetic dysfunction in renal and hepatic tissues. These findings suggest that understanding the balance between cyclodextrins’ efficacy and adverse effects is essential for better accepting their use in medicine