Lucian Hritcu

Changes of some oxidative stress markers in the serum of patients with mild cognitive impairment and Alzheimer's disease.

Mild cognitive impairment (MCI) is a nosological entity proposed as an intermediate state between normal aging and dementia. MCI seems to represent an early stage of Alzheimers disease (AD) and there is a great interest in the relationship between MCI and the progression to AD. Some studies have demonstrated an accumulation of products of free radical damage in the central nervous system and in the peripheral tissues of subjects with AD or mild cognitive impairment. The aim of the present work was to evaluate the serum levels of some enzymatic antioxidant defences like superoxide dismutase (SOD) and glutathione peroxidase (GPX), as well as lipid peroxidation markers like MDA (malondialdehyde), in MCI and AD patients, compared with age-matched healthy controls. The subjects of this study (45 patients) consisted of 15 individuals with mild cognitive impairment (MCI), 15 with Alzheimers disease (AD) and 15 healthy age-matched controls. Biochemical analyses showed a similar decrease of the main enzymatic antioxidant defences (SOD and GPX) and increased production of lipid peroxidation marker (MDA) in the serum of the MCI and AD patients, compared to age-matched control group. This study clearly demonstrates that oxidative stress damage occurs in patients with MCI and AD. Moreover, some enzymatic markers of oxidative stress are similar in MCI and AD patients, suggesting that oxidative damage could be one important aspect for the onset of AD.

Role of the mesotelencephalic dopamine system in learning and memory processes in the rat.

The effects of lesioning the ventral tegmental area or substantia nigra pars reticulata by means of bilateral microinjections of two doses of kainic acid (50 ng/250 nl and 100 ng/500 nl) or 6-hydroxydopamine (8 microg/4 microl) were investigated to clarify the role of the mesotelencephalic dopamine system in learning and memory processes. Our findings suggest that ventral tegmental area and substantia nigra dopaminergic neurons play an important role in retention of both short-term memory, tested in the Y-maze task and long-term memory evaluated with the multi-trial passive avoidance test, without affecting memory acquisition. As compared to short-term memory, long-term memory is more susceptible to the decreased dopamine level in nervous structures involved in processing and storage of information.

Brain serotonin depletion impairs short-term memory, but not long-term memory in rats

Intracerebroventricular injection of 5,7-dihydroxytryptamine (5,7-DHT) (150 microg; 4.5 microl/ventricle), a serotonergic neurotoxin, significantly decreased spontaneous alternation in Y-maze task and working memory in radial 8 arm-maze task, suggesting effects on short-term memory, without affecting long-term memory, explored by reference memory in radial 8 arm-maze task and step-through latency in multi-trial passive avoidance task. Parachlorophenylalanine (PCPA) (3 days treatment 200 microg, i.c.v.), a serotonin synthesis inhibitor, did not impair step-through-latency in multi-trial passive avoidance task, suggesting no effects on long-term memory. These results suggest that serotonin, among other neurotransmitters, play an important role in cognitive functions, especially short-term memory.

Effects of lavender oil inhalation on improving scopolamine-induced spatial memory impairment in laboratory rats.

Lavender is reported to be an effective medical plant in treating inflammation, depression, stress and mild anxiety in Europe and the USA. The present study investigated the effects of two different lavender essential oils from Lavandula angustifolia ssp. angustifolia Mill. (Lamiaceae) and Lavandula hybrida Rev. (Lamiaceae) on neurological capacity of male Wistar rats subjected to scopolamine (0.7mg/kg)-induced dementia rat model. Chronic exposures to lavender essential oils (daily, for 7 continuous days) significantly reduced anxiety-like behavior and inhibited depression in elevated plus-maze and forced swimming tests, suggesting anxiolytic and antidepressant activity. Also, spatial memory performance in Y-maze and radial arm-maze tasks was improved, suggesting positive effects on memory formation. Taken together, multiple exposures to lavender essential oils could effectively reverse spatial memory deficits induced by dysfunction of the cholinergic system in the rat brain and might provide an opportunity for management neurological abnormalities in dementia conditions.

Cognitive-enhancing and antioxidant activities of inhaled coriander volatile oil in amyloid β(1-42) rat model of Alzheimer's disease.

Coriandrum sativum L., commonly known as coriander and belonging to the Apiaceae family is cultivated throughout the world for its nutritional value. In traditional medicine, coriander is recommended for the relief of pain, anxiety, flatulence, loss of appetite and convulsions. In the present study, the effects of inhaled coriander volatile oil (1% and 3%, daily, for 21days) extracted from C. sativum var. microcarpum on spatial memory performance were assessed in an Aβ(1-42) rat model of Alzheimers disease. The Aβ(1-42)-treated rats exhibited the following: decrease of spontaneous alternations percentage within Y-maze task and increase of working memory errors, reference memory errors and time taken to consume all five baits within radial arm maze task. Exposure to coriander volatile oil significantly improved these parameters, suggesting positive effects on spatial memory formation. Assessments of oxidative stress markers in the hippocampal tissue of Aβ(1-42)-treated rats showed a significant increase of superoxide dismutase (SOD), lactate dehydrogenase (LDH) and a decrease of glutathione peroxidase (GPX) specific activities along with an elevation of malondialdehyde (MDA) level. Coriander volatile oil significantly decreased SOD and LDH specific activities, increased GPX specific activity and attenuated the increased MDA level. Also, DNA cleavage patterns were absent in the coriander rats, thus suggesting antiapoptotic activity of the volatile oil. Therefore, our results suggest that exposure to coriander volatile oil ameliorates Aβ(1-42)-induced spatial memory impairment by attenuation of the oxidative stress in the rat hippocampus.

Inhibition of central angiotensin II enhances memory function and reduces oxidative stress status in rat hippocampus.

While it is now well established that the independent brain renin-angiotensin system (RAS) has some important central functions besides the vascular ones, the relevance of its main bioactive peptide angiotensin II (Ang II) on the memory processes, as well as on oxidative stress status is not completely understood. The purpose of the present work was to evaluate the effects of central Ang II administration, as well as the effects of Ang II inhibition with either AT1 and AT 2 receptor specific blockers (losartan and PD-123177, respectively) or an angiotensin-converting enzyme (ACE) inhibitor (captopril). These effects were studied on the short-term memory (assessed through Y-maze) or long-term memory (as determined in passive avoidance) and on the oxidative stress status of the hippocampus. Our results demonstrate memory deficits induced by the administration of Ang II, as showed by the significant decrease of the spontaneous alternation in Y-maze (p=0.015) and latency-time in passive avoidance task (p=0.001) when compared to saline. On the other side, the administration of all the aforementioned Ang II blockers significantly improved the spontaneous alternation in Y-maze task, while losartan also increased the latency time as compared to saline in step-through passive avoidance (p=0.042). Also, increased oxidative stress status was induced in the hippocampus by the administration of Ang II, as demonstrated by increased levels of lipid peroxidation markers (malondialdehyde-MDA concentration) (p<0.0001) and a decrease in both antioxidant enzymes determined: superoxide dismutase-SOD (p<0.0001) and glutathione peroxidase-GPX (p=0.01), as compared to saline. Additionally, the administration of captopril resulted in an increase of both antioxidant enzymes and decreased levels of lipid peroxidation (p=0.001), while PD-123177 significantly decreased MDA concentration (p>0.0001) vs. saline. Moreover, significant correlations were found between all of the memory related behavioral parameters and the main oxidative stress markers from the hippocampus, which is known for its implication in the processes of memory and also where RAS components are well expressed. This could be relevant for the complex interactions between Ang II, behavioral processes and neuronal oxidative stress, and could generate important therapeutic approaches.

Methanolic extract of Hibiscus asper leaves improves spatial memory deficits in the 6-hydroxydopamine-lesion rodent model of Parkinson's disease.

ETHNOPHARMACOLOGICAL RELEVANCE While the Hibiscus asper Hook.f. (Malvaceae) is a traditional herb largely used in tropical region of the Africa as vegetable, potent sedative, tonic and restorative, anti-inflammatory and antidepressive drug, there is very little scientific data concerning the efficacy of this. AIM OF THE STUDY We investigated antioxidant activity and the effects of methanolic extract of Hibiscus asper leaves on neurological capacity of male Wistar rats subjected to unilateral 6-hydroxydopamine (6-OHDA)-lesion. MATERIALS AND METHODS Two model systems: 2,4-dinitrophenyl-1-picryl hydrazyl (DPPH) radical scavenging activity and β-carotene bleaching inhibition assay were used to measure the antioxidant activities of the plan extract. We also investigated the neuroprotective effect of methanolic extract of Hibiscus asper leaves (50 and 100 mg/kg) in male Wistar rats subjected to unilateral 6-hydroxydopamine (6-OHDA)-lesion rat model. RESULTS Methanolic extract of Hibiscus asper leaves showed potent antioxidant and free radical scavenging activity. Chronic administration of methanolic extract (50 and 100 mg/kg, i.p., daily, for 7 days) significantly reduce anxiety-like behavior and inhibit depression in elevated plus-maze and forced swimming tests, suggesting anxiolytic and antidepressant activity. Also, spatial memory performance in Y-maze and radial arm-maze tasks was improved, suggesting positive effects on memory formation. CONCLUSIONS Taken together, our results suggest that the methanolic extract of Hibiscus asper leaves have antioxidant effects and might provide an opportunity to management neurological abnormalities in Parkinsons disease conditions.

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.

Enhanced antibacterial effect of silver nanoparticles obtained by electrochemical synthesis in poly(amide-hydroxyurethane) media

In the present study, we report enhanced antimicrobial properties of 29 and 23 nm silver nanoparticles (Ag NPs) obtained by electrochemical synthesis in poly(amide-hydroxyurethane) media. Antibacterial activity assessed by disk diffusion method indicates that silver nanoparticles produced inhibition zones for both Escherichia coli and Staphylococcus aureus depending on silver concentration. The bacterial growth curve performed in the presence of silver nanoparticles showed a stronger antibacterial effect at lower concentrations than those described in the earlier reports. The effect was both dose and size dependent and was more pronounced against Gram negative bacteria than Gram positive one. The smallest Ag NPs used had a bactericidal effect resulting in killing E. coli cells. Scanning electron microscopy analysis indicated major damage and morphology changes of the silver nanoparticles treated bacterial cells. The major mechanism responsible for the antibacterial effect probably consists in clusters formation and nanoparticles anchorage to the bacterial cell surface.

Inhalation of coriander volatile oil increased anxiolytic–antidepressant-like behaviors and decreased oxidative status in beta-amyloid (1–42) rat model of Alzheimer's disease

The present study analyzed the possible anxiolytic, antidepressant and antioxidant proprieties of inhaled coriander volatile oil extracted from Coriandrum sativum var. microcarpum in beta-amyloid (1-42) rat model of Alzheimers disease. The anxiolytic- and antidepressant-like effects of inhaled coriander volatile oil were studied by means of in vivo (elevated plus-maze and forced swimming tests) approaches. Also, the antioxidant activity in the hippocampus was assessed using catalase specific activity and the total content of the reduced glutathione. The beta-amyloid (1-42)-treated rats exhibited the following: decrease of the locomotor activity, the percentage of the time spent and the number of entries in the open arm within elevated plus-maze test and decrease of swimming and immobility times within forced swimming test. Exposure to coriander volatile oil significantly improved these parameters, suggesting anxiolytic- and antidepressant-like effects. Moreover, coriander volatile oil decreased catalase activity and increased glutathione level in the hippocampus. Our results suggest that multiple exposures to coriander volatile oil can be useful as a mean to counteract anxiety, depression and oxidative stress in Alzheimers disease conditions.