The pathophysiologies of neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS), Parkinson’s disease (PD), and Alzheimer’s disease (AD), are far from being fully explained. Oxidative stress (OS) has been proposed as one factor that plays a potential role in the pathogenesis of neurodegenerative disorders. Clinical and preclinical studies indicate that neurodegenerative diseases are characterized by higher levels of OS biomarkers and by lower levels of antioxidant defense biomarkers in the brain and peripheral tissues. In this article, we review the current knowledge regarding the involvement of OS in neurodegenerative diseases, based on clinical trials and animal studies. In addition, we analyze the effects of the drug-induced modulation of oxidative balance, and we explore pharmacotherapeutic strategies for OS reduction.

The pathophysiology of psychiatric diseases, including depression, anxiety, schizophrenia and autism, is far from being fully elucidated. In recent years, a potential role of the oxidative stress has been highlighted in the pathogenesis of neuropsychiatric disorders. A body of clinical and preclinical evidence indicates that psychiatric diseases are characterized by higher levels of oxidative biomarkers and with lower levels of antioxidant defense biomarkers in the brain and peripheral tissues. In this article, we review current knowledge on the role of the oxidative stress in psychiatric diseases, based on clinical trials and animal studies, in addition, we analyze the effects of drug-induced modulation of oxidative balance and explore pharmacotherapeutic strategies for oxidative stress reduction.

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Oxidative stress is a dysfunctional state of living cells, caused by the disturbance of the pro-/antioxidative equilibrium. This dynamic equilibrium, constitutive for all aerobic organisms, is an inevitable necessity of maintaining the level of oxidative factors on non-destructive value to the cell. Among these factors reactive oxygen species (ROS) and reactive nitrogen species (RNS) are the best known molecules. This review article shows the current state of knowledge on the chemical specificity, relative reactivity and main sources of ROS and RNS in biological systems. As a Part 1 to the report about the role of oxidative stress in psychiatric disorders (see Smaga et al., Pharmacological Reports, this issue), special emphasis is placed on biochemical determinants in nervous tissue, which predisposed it to oxidative damage. Oxidative stress can be identified based on the analysis of various biochemical indicators showing the status of antioxidant barrier or size of the damage. In our article, we have compiled the most commonly used biomarkers of oxidative stress described in the literature with special regard to potentially effective in the early diagnosis of neurodegenerative processes.

In human addicts and in animal models, chronic cocaine use leads to numerous alterations in glutamatergic transmission, including its receptors. The present study focused on metabotropic glutamatergic receptors type 5 (mGluR5) and N-methyl-D-aspartate receptor subunits (NMDAR: GluN1, GluN2A, GluN2B) proteins during cocaine self-administration and after 10-day of extinction training in rats. To discriminate the contingent from the non-contingent cocaine delivery, we employed the “yoked”-triad control procedure. Protein expression in rat prefrontal cortex, nucleus accumbens, hippocampus, and dorsal striatum was determined. We also examined the Homer1b/c protein, a member of the postsynaptic density protein family that links NMDAR to mGluR5. Our results revealed that cocaine self-administration selectively increased GluN1 and GluN2A subunit in the rat hippocampus and dorsal striatum, respectively, while mGluR5 protein expression was similarly increased in the dorsal striatum of both experimental groups. Withdrawal from both contingent and non-contingent cocaine delivery induced parallel increases in prefrontal cortical GluN2A protein expression, hippocampal mGluR5, and GluN1 protein expression as well as in accumbal GluN1 subunit expression, while the mGluR5 expression was reduced in the prefrontal cortex. Extinction training in animals with a history of cocaine self-administration resulted in an elevation of the hippocampal GluN2A/GluN2B subunits and accumbal mGluR5, and in a 50 % decrease of mGluR5 protein expression in the dorsal striatum. The latter reduction was associated with Homer1b/1c protein level decrease. Our results showed that both contingent and non-contingent cocaine administration produces numerous, brain region specific, alterations in the mGluR5, NMDA, and Homer1b/1c protein expression which are dependent on the modality of cocaine administration.

Endothelial dysfunction is a common feature of early complications of hemato-oncologic therapy. The aim of our study was to assess the profile of endothelial function at diagnosis time, then during initial treatment phase of acute lymphoblastic leukemia (ALL), and to verify the presence of its correlation with early clinical outcome (ECO). 28 ALL children and 18 healthy age-matched control ones were recruited. Study group was examined at baseline and at 33rd and 78th day of treatment. At each protocol step the endothelial function was assessed by measurement of sP-selectin (CD62-P), PAI-1(serpinE1), sE-selectin (CD62E), sICAM-1(sCD54), sVCAM-1(sCD106), and VEGF concentrations. Higher baseline sICAM-1 and sVCAM-1 levels and lower sP-selectin and VEGF were observed in children with ALL. sICAM-1, sVCAM-1, and sE-selectin levels were decreasing following the treatment with protocol I. Higher sE-selectin and lower baseline sICAM-1 levels were observed in children treated unsuccessfully. Lower PAI-1 levels were observed in children who survived. Higher baseline sE-selectin levels and lower sICAM-1 and VEGF were observed in children treated unsuccessfully. A decrease in sE-selectin and lower PAI-1 at the 78th day of therapy were associated with better ECO. High baseline VEGF and sE-selectin levels, significant increase in PAI-1, and low initial sICAM-1 levels are prognostics for poorer prognosis in the ALL children.

This is the first demonstration that functionally assessed ED is present in ALL children at the diagnosis and results from elevated ADMA and parallel inflammatory ED.