No abstract

Changes in the content of fructose-2,6-bisphosphate, a modulator of glycolytic flux, also affect other metabolic fluxes such as the non-oxidative pentose phosphate pathway. Since this is the main source of precursors for biosynthesis in proliferating cells, PFK-2/FBPase-2 has been proposed as a potential target for neoplastic treatments. Here we provide evidence that cells with a low content of fructose-2,6-bisphosphate have a lower energy status than controls, but they are also less sensitive to oxidative stress. This feature is related to the activation of the oxidative branch of the pentose phosphate pathway and the increased production of NADPH. ß

NA. Laryngoscope, 127:561-567, 2017.

Severe hypoxia induces oxidative stress, which can lead to brain injury. In this study, we wanted to determine whether intermittent hypobaric hypoxia induces oxidative stress in the brain. In adult rats exposed to 380 mmHg in a hypobaric chamber for 3 h/day for 6 days, we determined the levels of malondialdehyde and nitric oxide derivatives in the brain, which indicated that there was no oxidative stress. The levels of N-acetylaspartate indicated that there was no neuronal loss or mitochondrial dysfunction and finally because apoptotic proteins such as caspase-3 and nuclear factor-kappa B (NF-κB) were not activated, apoptosis was probably not induced. The increase in the expression of erythropoietin (EPO) in the brain of rats exposed to hypoxia confirms the efficacy of the method used to induce hypoxia in the brain. Because EPO have antioxidant effects on the brain, the results suggest that intermittent hypoxia can increase the antioxidant capacity of the brain. This effect of intermittent hypoxia was studied using the systemic administration of kainate, as a model of brain oxidative stress. Kainate treatment induces oxidative stress in the brain, which is measured by an increase in lipid peroxidation and nitric oxide. Furthermore, in rats treated with kainate, both caspase-3 and NF-κB activity increased. However, in rats previously exposed to intermittent hypobaric hypoxia, 3 h per day for 6 days, the effect of kainate treatment resulted in the reduction of both oxidative stress and apoptotic activity. This study demonstrates that intermittent hypobaric hypoxia can increase brain antioxidant capacity in rats and induces neuroprotection in kainate-induced oxidative injury.

Experimental and clinical data suggest that iron has a key role in cerebral ischaemia. We measure infarct volume and analyse the nitric oxide responses to brain injury in rat stroke model after increased oral iron intake. Permanent middle cerebral artery occlusion (MCAO) was performed in a group of 20 male Wistar rats, 10 of which were fed with a control diet and 10 of which were fed with iron-enriched diet containing 2.5% carbonyl iron for 9 weeks. L-arginine and nitric oxide metabolites were determined in blood samples before and at 2, 6, 8 and 48 h after MCAO. Infarct volume, thiobarbituric acid reaction substances (TBARS) and tissue iron were measured at 48 h. Infarct volume was 66% greater in the iron-fed rats than in the control group. Iron-fed animals showed significantly higher levels of TBARS. Liver iron stores (3500 +/- 199 vs 352 +/- 28 microg Fe/g, p<0.0001) but not brain iron stores (131 +/- 11 vs 139 +/- 8 microg Fe/g, p=0.617), were significantly higher in the iron-fed group. L-arginine levels were slightly lower in iron-fed rats and decreased significantly in both groups at 6 and 8 hours after MCAO. The levels of the stable end products of NOS (NOx = nitrite + nitrate) were significantly higher in iron-fed rats before MCAO (16.2 +/- 2.2 vs. 9.6 +/- 0.8 micromol x L(-1), p<0.05), with a further increase during the six first hours after MCAO in both groups. These results suggest that the iron overload that increases both superoxide and nitric oxide production leads to peroxynitrite formation, thus enhancing brain damage.