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.
Kratak sadr`aj: Ispitivan je uticaj intracere bro ventrikularne administracije angiotenzina II i kaptoprila na napetost i oksidativni stres u mozgu. Za procenjivanje po na{anja bliskog anksioznosti kori{}en je test uzdignutog lavirinta u obliku znaka plus, dok je biohemijska analiza obu hvatila odre|ivanje nekih enzima antioksidantne odbrane kao {to su superoksid-dismutaza i glutation-peroksidaza i pro izvoda lipidne peroksidacije (malondialdehid). Na{i re zultati predstavljaju jo{ jedan dokaz da angiotenzin II iza ziva posledice nalik na anksioznost i povi{en prooksidantni sta tus.[tavi{e, blokiranje angiotenzina II davanjem inhibitora enzima koji konvertuje angiotenzin (kaptoprila) delo valo je kao anksiolitik i dovelo do sni`enja statusa oksi dativnog stresa. Pored toga, otkrivena je zna~ajna korelacija izme |u vremena koje su pacovi proveli u otvorenim »ruka ma« lavirinta i markera oksidativnog stresa. Ovo mo`da uka zuje na va`nost pokretanja nekih va`nih terapijskih pita nja koja se ti~u anksioliti~kog dejstva nekih inhibitora enzi ma koji konvertuju angiotenzin a koji se pre svega koriste za hipertenziju, kakav je kaptopril. Tako|e, sva je prilika da oksi dativni stres u tome igra va`nu ulogu.
One of the most widely used animal models of Parkinson's disease (PD) involves injecting 6-hydroxydopamine (6-OHDA) directly into the substantia nigra (SN). Some recent reports speculated that dopaminergic drugs may exert brain antioxidant activity, which could explain some of their protective actions. In this way, the aim of the present study was to examine the effects of low-dose pergolide on memory deficits and brain oxidative stress in a 6-OHDA-induced rat model of PD. Right-unilateral lesions of the SN were produced with 6-OHDA. Two weeks after neurosurgery, pergolide (0.3 mg/kg/day) was injected intraperitoneally in the 6-OHDA + pergolide and sham-operated + pergolide groups, while sham-operated and 6-OHDA alone groups received saline. Radial-8-arm maze and Y-maze were used for memory assessment. We also determined some enzymatic antioxidant defenses like superoxide dismutase or glutathione peroxidase and a lipid peroxidation marker [malondialdehyde (MDA)], from the temporal lobe. A reduced number of working/reference memory errors was observed in 6-OHDA + pergolide group, compared to sham-operated rats. Additionally, post hoc analysis showed significant differences between 6-OHDA and 6-OHDA + pergolide groups in both Y-maze and radial-arm-maze tasks. We also noted a significant decrease of MDA level in the 6-OHDA + pergolide group, compared to sham-operated rats. Significant correlations were also found between behavioral parameters and MDA levels. Our data suggest that pergolide facilitates spatial memory and improves brain oxidative balance, after a 6-OHDA-induced model of PD. This could be useful for further investigations and clinical applications of pergolide.
AbstractIn 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 suicidal behavior is regarded as the act by which a person seeks to take his life, being aware of the consequences of his action. In our review, besides describing the main introductory aspects for the concept of suicide, we focus our attention on the main neurophysiological and genetical mechanisms relevant for this extremely difficult to manage and controversial behavior. Moreover, considering the latest interests in the current literature on the relevance of central oxytocin to various superior cognitive behaviors, we will also make a short description on how important effects of oxytocin could be in the context of suicidal behavior.
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