Veronica Bild

Effects of serotonin depletion on behavior and neuronal oxidative stress status in rat: relevance for anxiety and affective disorders

PURPOSE We lesioned the hypothalamic paraventricular nucleus (PVN) of male Wistar rats using two different doses (8μg/3μl and 16μg/3μl) of 5,7-dihydroxytryptamine (5,7-DHT) and then animals were subjected to a battery of behavioral tests designed to assess anxiety and memory formation. Further, we were interested to know whether this lesion would result in neuronal oxidative stress and also if there is a correlation between the behavioral response to this lesion and brain oxidative stress. MATERIAL/METHODS Behavioral tests included elevated plus maze, used to assess exploration/anxiety status and radial armmaze, used for determining spatial short-term and reference memory errors. Regarding the oxidative stress, we measured the extent of some lipid peroxidation products like malondialdehyde and defense enzymes such as superoxide dismutase and glutathione peroxidase. RESULTS 5,7-DHT lesioned rats spent more time in the open arms of the elevated maze compared to sham-operated rats, suggesting that the lesion significantly diminished anxiety-like behavior. Also, short-term memory was significantly impaired, as shown by the working memory errors in radial arm-maze task. Further analyses revealed that the 5,7-DHT lesion did not result in a significant change of reference memory errors. Regarding the oxidative stress, no significant modification of both superoxide dismutase and glutathione peroxidase specific activities from the temporal lobe were observed. However, the malondiadehyde level was significantly increased, suggesting pro-oxidant effects. Also, the linear regression between the working memory errors vs. malondiadehyde resulted in significant correlations. CONCLUSION 5,7 DHT lesion of the PVN affects behavioral performance via interactions with systems governing novel and/or fear-evoking situations and also by increasing neuronal oxidative stress.

Effects of angiotensin II receptor antagonists on anxiety and some oxidative stress markers in rat

In addition to its known classical roles, the renin angiotensin system (RAS) has more subtle functions which include the regulation of emotional responses. Previous studies regarding the anxiety related behavior of RAS have showed controversial results. There is also evidence that oxidative stress accompanies angiotensin II infusion, but the role of AT1/AT2 specific receptors is not clear. The aim of this study was to evaluate the effects of central angiotensin II receptor blockers on anxiety state and oxidative stress. Behavioral testing included elevated plus maze, while oxidative stress status was measured though the extent of a lipid peroxidation product (malondialdehyde-MDA) and the specific activity of some defense antioxidant enzymes (superoxide dismutase-SOD and glutathione peroxidase-GPx). The rats treated with angiotensin II spent significantly less time in the open-arms of elevated-plus-maze, while the administration of losartan resulted in a significant increase of this time. We observed a significant increase of MDA concentration in the angiotensin II group and a decrease of MDA levels in both losartan and PD-123177 groups. In addition, a significant correlation was seen between the time spent in the open arms and oxidative stress markers. These findings could lead to important therapeutic aspects regarding the use of angiotensin II receptor blockers in anxiety-related disorders.

The interdependence of the reactive species of oxygen, nitrogen, and carbon.

This mini-review tries to summarize the main interdependences between the free radicals of oxygen, nitrogen, and carbon. Also, the main metabolic pathways for these radical species are described, as well as how these affect their interaction and functional implications. Emphasis is made on the metabolic disturbances induced by stressing aggressions that produce radical species. In this way, cellular oxidative imbalances created by the superiority of reactive oxygen species over the antioxidant systems produce both activation of nitroxide synthases and the oxidation of terminal nitrogen from l-arginine, as well as the metabolization of heme until carbon monoxide by nitric oxide-activated hemoxygenase. Also, multiple cellular protein and nucleoprotein alterations determined by these three kinds of radical species are completed by the involvement of hydrogen sulfide, which results from the degradation of l-cysteine by cistationine-γ-lyase. In this way, sufficient experimental data tend to demonstrate the involvement of hydrogen sulfide and other thiol derivatives in the interrelations between oxygen, nitrogen, and carbon, which results in a true radical cascade. Thus, oxidative stress, together with nitrosative and carbonilic stress, may constitute a central point where other factors of vulnerability meet, and their interactions could have an important impact in many modern diseases. Considering that the actions of reactive species can be most of the time corrected, future studies need to establish the therapeutical importance of various agents which modulate oxidative, nitrosative, or carbonilic stress.

Vernonia kotschyana Roots: Therapeutic Potential via Antioxidant Activity

The roots of Vernonia kotschyana Sch. Bip. ex Walp. (Asteraceae) are used in Malian traditional medicine in the treatment of gastroduodenal ulcers and gastritis. Since oxidative stress is involved in gastric ulceration, the aim of this study was to screen the root extracts for their in vitro antioxidant activity and phenolic content. The roots were extracted successively with chloroform, ethyl acetate, ethanol and water. The antioxidant activity of root extracts was evaluated in both cell-free and cell-based assays. Their chemical characterization was performed by Fourier transform infrared spectroscopy (FT-IR) whereas the total phenolic content was determined by the Folin-Ciocalteu method. The ethyl acetate extract displayed the highest phenolic content and was found to be the most active in the free radical scavenging and lipid peroxidation inhibition assays; it also showed a high antioxidant activity in MCF-12F cells. This study suggests a potential use of the ethyl acetate extract of Vernonia kotschyana not only as an antioxidant agent in gastroduodenal ulcers and gastritis, but also in other disorders characterized by high levels of oxidative stress.

New evidence for vascular interactions between aldosterone, angiotensin II and antioxidants in isolated smooth muscle cells of rats

Accumulating evidence suggests that the nongenomic cardiovascular actions of aldosterone are produced by varied cellular pathways and mediated by a multitude of messenger systems including the reactive oxygen and nitrogen species. Considering the involvement of the oxidative and nitrosative stress in the pathways leading to the activation of the angiotensin — aldosterone system, in the current study we tried to evaluate the functional interactions between aldosterone, angiotensin II and antioxidants in isolated vascular smooth muscle of aortic rings from rats. Our data provide additional arguments that the nongenomic actions of aldosterone on aortic smooth muscle cells of rats are a question of cross-talk and balance between its rapid vasoconstrictor and vasodilator effects, as result of the activation of reactive oxygen species in the first case and of nitrogen species in the second. In this way, it seems that at low ambient oxidative stress, aldosterone promotes nitric oxide (NO) production and vasodilatation, while in situations with increased oxidative stress the endothelial dysfunction and detrimental effects induced by vasoconstriction will prevail. Thus, aldosterone could be considered both “friend and foe”. This could be relevant for the ways in which aldosterone damages cardiovascular functions and could lead to significant therapeutic improvements.

The effects of angiotensin II and angiotensin 1-7 in cognitive processes and oxidative stress in rats. Relevance for Alzheimer's disease

(VROI). Hippocampal and dorsolateral frontal (DLFC) cortex VROIs were selected from the SPM sub-utility ‘Pickatlas’. In each subject, mean FDG uptake values within VROIs was computed using Mask subtool of SPM and normalized to the cerebellar uptake. Both in patients and controls, normalized VROI values were used as dependent variables in multiple regression analyses to search for metabolic correlations (connectivity) with the whole brain (uncorrected p < 0.001 at peak level and p < 0.05 FDR-corrected at cluster level). Correlation analysis was repeated in an independent group of 69 healthy subjects.Results:As compared to controls, pAD showed relative hypometabolism in precuneus, posterior cingulate gyrus and superior parietal lobule in both hemispheres. This hypometabolic area showed less metabolic connectivity in pAD with respect to CTR (autocorrelation versus wide correlation with temporal and frontal lobes, respectively). PAD showed limited correlation even innon-hypometabolic areas. Both hippocampi showed correlation with controlateral homologues only, while in CTR correlation was highlighted with precuneus/ posterior cingulate and frontal cortex. Similarly, DLFC correlation was limited to ipsilateral frontal cortex, while involving caudate nuclei and parietal cortex in CTR. Results in CTR were confirmed in the wider sample of 69 subjects. Conclusions: Metabolic connectivity is impaired in pAD. The reduced metabolic connections both in hypometabolic and non-hypometabolic areas suggest that metabolic disconnection (possible sign of degeneration at synaptic level) may antedates hypometabolism (early sign of neuronal death).