Brain bioenergetics in rats with acute hyperphenylalaninemia.

Phenylketonuria (PKU) is a disorder of phenylalanine (Phe) metabolism caused by deficient phenylalanine hydroxylase (PAH) activity. The deficiency results in increased levels of Phe and its metabolites in fluids and tissues of patients. PKU patients present neurological signs and symptoms including hypomyelination and intellectual deficit. This study assessed brain bioenergetics at 1 h after acute Phe administration to induce hyperphenylalaninemia (HPA) in rats. Wistar rats were randomized in two groups: HPA animals received a single subcutaneous administration of Phe (5.2 µmol/g) plus p-Cl-Phe (PAH inhibitor) (0.9 µmol/g); control animals received a single injection of 0.9% NaCl. In cerebral cortex, HPA group showed lower mitochondrial mass, lower glycogen levels, as well as lower activities of complexes I-III and IV, ATP synthase and citrate synthase. Higher levels of free Pi and phospho-AMPK, and higher activities of LDH, α-ketoglutarate dehydrogenase and isocitrate dehydrogenase were also reported in cerebral cortex of HPA animals. In striatum, HPA animals had higher LDH (pyruvate to lactate) and isocitrate dehydrogenase activities, and lower activities of α-ketoglutarate dehydrogenase and complex IV, as well as lower phospho-AMPK immunocontent. In hippocampus, HPA rats had higher mRNA expression for MFN1 and higher activities of α-ketoglutarate dehydrogenase and isocitrate dehydrogenase, but decreased activities of pyruvate dehydrogenase and complexes I and IV. In conclusion, our data demonstrated impaired bioenergetics in cerebral cortex, striatum and hippocampus of HPA rats.

Effects of Acerola (Malpighia emarginata DC.) Juice Intake on Brain Energy Metabolism of Mice Fed a Cafeteria Diet.

Obesity is a multifactorial disease that comes from an imbalance between food intake and energy expenditure. Moreover, studies have shown a relationship between mitochondrial dysfunction and obesity. In the present study, we investigated the effect of acerola juices (unripe, ripe, and industrial) and its main pharmacologically active components (vitamin C and rutin) on the activity of enzymes of energy metabolism in the brain of mice fed a palatable cafeteria diet. Two groups of male Swiss mice were fed on a standard diet (STA) or a cafeteria diet (CAF) for 13 weeks. Afterwards, the CAF-fed animals were divided into six subgroups, each of which received a different supplement for one further month (water, unripe, ripe or industrial acerola juices, vitamin C, or rutin) by gavage. Our results demonstrated that CAF diet inhibited the activity of citrate synthase in the prefrontal cortex, hippocampus, and hypothalamus. Moreover, CAF diet decreased the complex I activity in the hypothalamus, complex II in the prefrontal cortex, complex II-III in the hypothalamus, and complex IV in the posterior cortex and striatum. The activity of succinate dehydrogenase and creatine kinase was not altered by the CAF diet. However, unripe acerola juice reversed the inhibition of the citrate synthase activity in the prefrontal cortex and hypothalamus. Ripe acerola juice reversed the inhibition of citrate synthase in the hypothalamus. The industrial acerola juice reversed the inhibition of complex I activity in the hypothalamus. The other changes were not reversed by any of the tested substances. In conclusion, we suggest that alterations in energy metabolism caused by obesity can be partially reversed by ripe, unripe, and industrial acerola juice.

Gold nanoparticles alter parameters of oxidative stress and energy metabolism in organs of adult rats.

This study evaluated the parameters of oxidative stress and energy metabolism after the acute and long-term administration of gold nanoparticles (GNPs, 10 and 30 nm in diameter) in different organs of rats. Adult male Wistar rats received a single intraperitoneal injection or repeated injections (once daily for 28 days) of saline solution, GNPs-10 or GNPs-30. Twenty-four hours after the last administration, the animals were killed, and the liver, kidney, and heart were isolated for biochemical analysis. We demonstrated that acute administration of GNPs-30 increased the TBARS levels, and that GNPs-10 increased the carbonyl protein levels. The long-term administration of GNPs-10 increased the TBARS levels, and the carbonyl protein levels were increased by GNPs-30. Acute administration of GNPs-10 and GNPs-30 increased SOD activity. Long-term administration of GNPs-30 increased SOD activity. Acute administration of GNPs-10 decreased the activity of CAT, whereas long-term administration of GNP-10 and GNP-30 altered CAT activity randomly. Our results also demonstrated that acute GNPs-30 administration decreased energy metabolism, especially in the liver and heart. Long-term GNPs-10 administration increased energy metabolism in the liver and decreased energy metabolism in the kidney and heart, whereas long-term GNPs-30 administration increased energy metabolism in the heart. The results of our study are consistent with other studies conducted in our research group and reinforce the fact that GNPs can lead to oxidative damage, which is responsible for DNA damage and alterations in energy metabolism.

Effects of acute administration of mazindol on brain energy metabolism in adult mice.

OBJECTIVES: Mazindol is a sympathomimetic amine, widely used as an anorectic agent in the treatment of obesity. This drug causes psychostimulant effects because of its pharmacological profile similar to amphetamine, acting like a monoamine reuptake inhibitor. However, the mechanisms underlying the action of mazindol are still not clearly understood. METHODS: Swiss mice received a single acute administration of mazindol (0.25, 1.25 and 2.5 mg/kg, ip) or saline. After 2 h, the animals were killed by decapitation; the brain was removed and used for the evaluation of activities of mitochondrial respiratory chain complexes, Krebs cycle enzymes and creatine kinase. RESULTS: Acute administration of mazindol decreased complex I activity only in the hippocampus. Complex IV activity was increased in the cerebellum (2.5 mg/kg) and cerebral cortex (0.25 mg/kg). Citrate synthase activity was increased in the cerebellum (1.25 mg/kg) and cerebral cortex (1.25 mg/kg), and creatine kinase activity was increased in the cerebellum (1.25 mg/kg). CONCLUSION: We suggest that the inhibition of complex I in the hippocampus only and activation of complex IV, citrate synthase and creatine kinase occurs because of a stimulus effect of mazindol in the central nervous system, which causes a direct impairment on energy metabolism.