Changes in the Oxidative Status of Dual-Purpose Hens Rearing in the Free-Range System during Cold, Thermoneutral and Hot Period.

This study aimed to assess the changes in the oxidative status of six genotypes of free-range laying hens during cold, thermoneutral, and hot periods by measuring the levels of lipid peroxidation (LPO), total glutathione (tGSH), and the activity of antioxidant enzymes catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx) in erythrocyte suspension, in relation with their egg production. Two identical experiments were conducted in two consecutive years. Thermal stress adversely affected the oxidative status of hens. The induced OS is expressed by an increase in LPO and the activities of antioxidant enzymes SOD and GPx during cold and hot periods and a decrease in CAT and tGSH during the cold period in both years. The factor "temperature period", compared to "year" and "genotype", had the most significant influence on all biochemical parameters (p < 0.001). Significant phenotypic correlations (p < 0.05) were detected among studied biochemical parameters, except between SOD and tGSH. The chicken genotypes showed differences in their susceptibility to OS and this had an effect on egg production­from 37.87% to 74.93%. The OS is genotypically specific and can play a significant role in determining welfare and egg production in free-range systems.

New Myrtenal-Adamantane Conjugates Alleviate Alzheimer's-Type Dementia in Rat Model.

Alzheimer's disease (AD) is a neurodegenerative disease associated with memory impairment and other central nervous system (CNS) symptoms. Two myrtenal-adamantane conjugates (MACs) showed excellent CNS potential against Alzheimer's models. Adamantane is a common pharmacophore for drug design, and myrtenal (M) demonstrated neuroprotective effects in our previous studies. The aim of this study is to evaluate the MACs' neuroprotective properties in dementia. METHODS: Scopolamine (Scop) was applied intraperitoneally in Wistar rats for 11 days, simultaneously with MACs or M as a referent, respectively. Brain acetylcholine esterase (AChE) activity, noradrenaline and serotonin levels, and oxidative brain status determination followed behavioral tests on memory abilities. Molecular descriptors and docking analyses for AChE activity center affinity were performed. RESULTS: M derivatives have favorable physicochemical parameters to enter the CNS. Both MACs restored memory damaged by Scop, showing significant AChE-inhibitory activity in the cortex, in contrast to M, supported by the modeling analysis. Moderate antioxidant properties were manifested by glutathione elevation and catalase activity modulation. MACs also altered noradrenaline and serotonin content in the hippocampus. CONCLUSION: For the first time, neuroprotective properties of two MACs in a rat dementia model were observed. They were stronger than the natural M effects, which makes the substances promising candidates for AD treatment.

Anti-Coronavirus Efficiency and Redox-Modulating Capacity of Polyphenol-Rich Extracts from Traditional Bulgarian Medicinal Plants.

Background: The use of various herbal therapists as part of traditional medicine in different parts of the world, including Bulgaria, is due to the knowledge accumulated over the centuries by people about their valuable biological activities. In this study, we investigate extracts from widely used Bulgarian medicinal plants for their ability to prevent the coronavirus infection of cells by testing different mechanisms of antiviral protection, their polyphenol content, and redox-modulating capacity. Methods: The influence on the stage of viral adsorption, the inhibition of extracellular virions, and the protective effect on uninfected cells of the plant's extracts were reported by the end-point dilution method, and virus titer (in Δ lgs) was determined as compared to the untreated controls. The total content of polyphenols and flavonoids was also determined. We tested the antioxidant power of the extracts by their ability to inhibit the generation of superoxide anionic radicals and to scavenge DPPH radicals. We determined their iron-reducing, copper-reducing, and metal-chelating antioxidant powers. Results: Most of the extracts tested suppress the extracellular virions of HCov. They also inhibit the stage of viral adsorption to the host cell to varying degrees and have a protective effect on healthy cells before being subjected to viral invasion. The examined extracts contained significant levels of polyphenols and quercetin-like flavonoids and showed remarkable antioxidant, radical, and redox-modulating effects. Conclusions: All of these 13 extracts from Bulgarian medicinal plants tested can act as antioxidants and antiviral and symptomatic drugs for the management of coronavirus infection.

Beneficial Effects of Snail Helix aspersa Extract in an Experimental Model of Alzheimer's Type Dementia.

BACKGROUND: Alzheimer's disease (AD) is a complex neurodegenerative disease with multifactorial etiology, unsatisfactory treatment, and a necessity for broad-spectrum active substances for cure. The mucus from Helix aspersa snail is a mixture of bioactive molecules with antimicrobial, anti-inflammatory, antioxidant, and anti-apoptotic effects. So far there are no data concerning the capacity of snail extract (SE) to affect neurodegenerative disorders. OBJECTIVE: The effects of SE from Helix aspersa on learning and memory deficits in Alzheimer's type dementia (ATD) induced by scopolamine (Sco) in male Wistar rats were examined and some mechanisms of action underlying these effects were evaluated. METHODS: SE (0.5 mL/100 g) was applied orally through a food tube for 16 consecutive days: 5 days before and 11 days simultaneously with Sco (2 mg/kg, intraperitoneally). At the end of Sco treatment, using behavioral methods, we evaluated memory performance. Additionally, in cortex and hippocampus the acetylcholinesterase (AChE) activity, acetylcholine and monoamines (dopamine, noradrenaline, and serotonin) content, levels of main oxidative stress markers, and expression of brain-derived neurotrophic factor (BDNF) and cAMP response element-binding protein (CREB) were determined. RESULTS: We demonstrated that, according to all behavioral tests used, SE significantly improved the cognitive deficits induced by Sco. Furthermore, SE possessed AChE inhibitory activity, moderate antioxidant properties and the ability to modulate monoamines content in two brain structures. Moreover, multiple SE applications not only restored the depressed by Sco expression of CREB and BDNF, but significantly upregulated it. CONCLUSION: Summarizing results, we conclude that complex mechanisms underlie the beneficial effects of SE on impaired memory in Alzheimer's type dementia.

Neuroprotective Effects of Myrtenal in an Experimental Model of Dementia Induced in Rats.

There is growing attention on natural substances capable of stimulating the cholinergic system and of exerting antioxidant effects, as potential therapeutic agents in Alzheimer's disease (AD). The aim of the present study is to evaluate the expected neuroprotective mechanisms of myrtenal (M) in an experimental model of dementia in rats. Dementia was induced in male Wistar rats by scopolamine (Sc) administration (0.1 mg/kg for 8 days and 20.0 mg/kg on day 9). The animals were divided into 5 groups (1) Controls; (2) Sc; (3) Sc + Myrtenal (40 mg/kg), (4) Sc + Galantamine (1 mg/kg); (5) Sc + Lipoic acid (30 mg/kg). Changes in recognition memory and habituation were evaluated via the Novel Object Recognition and Open Field tests. Acetylcholinesterase (AChE) activity, ACh levels, and changes in oxidative status of the brain were measured biochemically. The histological changes in two brain regions-cortex and hippocampus, were evaluated qualitatively and quantitatively. Myrtenal improved recognition memory and habituation, exerted antioxidant effects and significantly increased ACh brain levels. Histologically, the neuroprotective capacity of myrtenal was also confirmed. For the first time, we have demonstrated the neuroprotective potential of myrtenal in an experimental model of dementia. Our study provides proof-of-concept for the testing of myrtenal, in association with standard of care treatments, in patients affected by cognitive decline.

Tyrosinyl-amantadine: A New Amantadine Derivative With an Ameliorative Effect in a 6-OHDA Experimental Model of Parkinson's Disease in Rats.

The neuroprotective capacity of newly synthesized amantadine derivative tyrosinyl-amantadine (Tyr-Am) with expected antiparkinsonian properties was evaluated in a 6-hydroxydopamine (6-OHDA) model of Parkinson's disease. Male Wistar rats were divided into the following groups: sham-operated (SO), striatal 6-OHDA-lesioned control group, 6-OHDA-lesioned rats pretreated for 6 days with Tyr-Am (16 mg/kg administered intraperitoneally, i.p.), and 6-OHDA-lesioned rats pretreated for 6 days with amantadine (40 mg/kg i.p.), used as a referent. On the first, second and third week post-lesion, the animals were subjected to some behavioral tests (apomorphine-induced rotation, rotarod, and passive avoidance test). The acetylcholinesterase (AChE) activity and key oxidative stress parameters including lipid peroxidation levels (LPO) and superoxide dismutase (SOD) were measured in brain homogenates. The results showed that the neuroprotective effect of Tyr-Am was comparable to that of amantadine, improving neuromuscular coordination and learning and memory performance even at a 2.5-fold lower dose. Tyr-Am demonstrated significant antioxidant properties via decreased LPO levels but had no effect on AChE activity. We can conclude that the newly synthesized amantadine derivative Tyr-Am demonstrated significant antiparkinsonian activity in a 6-OHDA experimental model.

Neuroprotective Mechanisms of Three Natural Antioxidants on a Rat Model of Parkinson's Disease: A Comparative Study.

We compared the neuroprotective action of three natural bio-antioxidants (AOs): ellagic acid (EA), α-lipoic acid (LA), and myrtenal (Myrt) in an experimental model of Parkinson's disease (PD) that was induced in male Wistar rats through an intrastriatal injection of 6-hydroxydopamine (6-OHDA). The animals were divided into five groups: the sham-operated (SO) control group; striatal 6-OHDA-lesioned control group; and three groups of 6-OHDA-lesioned rats pre-treated for five days with EA, LA, and Myrt (50 mg/kg; intraperitoneally- i.p.), respectively. On the 2nd and the 3rd week post lesion, the animals were subjected to several behavioral tests: apomorphine-induced rotation; rotarod; and the passive avoidance test. Biochemical evaluation included assessment of main oxidative stress parameters as well as dopamine (DA) levels in brain homogenates. The results showed that all three test compounds improved learning and memory performance as well as neuromuscular coordination. Biochemical assays showed that all three compounds substantially decreased lipid peroxidation (LPO) levels, and restored catalase (CAT) activity and DA levels that were impaired by the challenge with 6-OHDA. Based on these results, we can conclude that the studied AOs demonstrate properties that are consistent with significant antiparkinsonian effects. The most powerful neuroprotective effect was observed with Myrt, and this work represents the first demonstration of its anti-Parkinsonian impact.

Effects of desipramine on the antioxidant status in rat tissues at carrageenan-induced paw inflammation.

The pathogenesis of many diseases and different pathological conditions, including inflammation, is associated with excess production of reactive oxygen species (ROS). The present study aimed to investigate the effects of the antidepressant desipramine (DES) on carrageenan (CG)-induced inflammation, as well as on the endogenous levels of cell enzyme and non-enzyme antioxidants in rat liver and spleen, 4 and 24 h after CG injection. The intra-plantar CG injection into the right hind paw resulted in a time-dependent increase in the paw volume; the maximum of CG-induced edema peak was in 2-4 h. A single DES dose of 20 mg · kg(-1) , administered 30 min before CG, had no effect on paw edema, whereas the higher drug dose used (50 mg · kg(-1) ) suppressed the edematous response to CG. The latter drug dose protected CG-induced decrease of glutathione (non-enzyme antioxidant) in the liver; it did not affect CG-unchanged activities of superoxide dismutase, glutathione peroxidase (enzyme antioxidants) and glucose-6-phosphate dehydrogenase (enzyme, important for the activity of glutathione-conjugated antioxidant enzymes) in both liver and spleen. The drug showed an efficient antioxidant capacity in ROS-generating chemical systems; it was higher than that of fluoxetine (another type of antidepressant). The present results suggest that the good antioxidant activity of DES might contribute to its beneficial effects in liver injuries.

Effects of structural analogues of nociceptin(1-13)NH2 on brain antioxidant status in kainic acid-treated rats.

The in vivo effects of nociceptin (N/OFQ(1-13)NH(2) ) and its structural analogues ([Dab(9) ]N/OFQ(1-13)NH(2) , [Dap(9) ]N/OFQ(1-13)NH(2) and [Cav(9) ]N/OFQ(1-13)NH(2) ) on the levels of lipid peroxidation and cell antioxidants (enzyme and non-enzyme) in brain of control and kainic acid (KA)-treated rats were studied. In control animals, [Dab(9) ]N/OFQ(1-13)NH(2) and [Dap(9) ]N/OFQ(1-13)NH(2) , unlike N/OFQ(1-13)NH(2) and [Cav(9) ]N/OFQ(1-13)NH(2) , slightly increased the brain lipid peroxidation; the rest of the parameters were unchanged by all neuropeptides tested. KA (0.25 µg in 0.5 µl, i.c.v) increased the lipid peroxidation (4 and 24 h after KA-injection) and decreased the glutathione level (1 h after KA-administration). One hour after KA-administration, the neuropeptides (2 µg in 0.5 µl, injected 30 min before KA) showed the following effects: a slight decrease in the KA-induced lipid peroxidation by all nociceptin analogues and an enhancement of the KA-decreased GSH level, but by [Cav(9) ]N/OFQ(1-13)NH(2) only. The brain antioxidant enzyme activities were unchanged in all used experimental groups. In addition, the nociceptin analogues, especially [Can(9) ]N/OFQ(1-13)NH(2) , showed a good antioxidant capacity in chemical systems, generating reactive oxygen species. In conclusion, the substitution of lysin (Lys) in N/OFQ(1-13)NH(2) molecule with other amino acids might contribute to changes in its antioxidant properties. Copyright © 2011 John Wiley & Sons, Ltd.

Antioxidant activity of fluoxetine: studies in mice melanoma model.

In vivo effects of the antidepressant fluoxetine on spleen antioxidant status of C57BL/6 mice were studied using a melanoma experimental model. After a 14-day treatment with fluoxetine (10 mg kg(-1) day(-1), i.p.), the endogenous antioxidant non-enzyme (glutathione) and enzyme (superoxide dismutase (SOD) and glutathione peroxidase (GPx)) defense systems in spleen of healthy animals were not changed; the lipid peroxidation (LP) was also unchanged. When B16F10 melanoma cells were introduced in C57BL/6 mice 2 h before fluoxetine treatment, a drug-protective effect against the melanoma-induced oxidative changes (increased LP and decreased total glutathione (GSH)-level, as well as antioxidant enzyme activities) in spleen was observed. Fluoxetine dose-dependently reduced the amounts of free oxygen radicals (hydroxyl and superoxide anion radicals), generated in chemical systems. Taken together, the present results suggest that fluoxetine, acting as antioxidant, prevents from melanoma-induced oxidative changes in mice spleen.

Are nociceptin(1-13)NH2 and its structural analogue [ORN(9)]nociceptin(1-13)NH2 able to affect brain antioxidant status in control and kainic acid-treated rats?

In-vivo effects of nociceptin (N/OFQ(1-13)NH(2)) on the levels of lipid peroxidation and cell enzyme (superoxide dismutase, glutathione peroxidase and glutathione reductase) and non-enzyme (glutathione) antioxidants in brain of control and kainic acid-treated rats were studied. N/OFQ(1-13)NH(2) effects were compared with those of its structural analogue [Orn(9)]N/OFQ(1-13)NH(2). Kainic acid (25 microg, i.c.v) increased the lipid peroxidation (4 and 24 h after kainic acid treatment) and decreased the glutathione level (1 h after kainic acid injection). We failed to find, any changes in antioxidant enzyme activities, independently of the time of kainic acid treatment. At the background of kainic acid-effects, N/OFQ(1-13)NH(2) and [Orn(9)] N/OFQ(1-13)NH(2), injected 30 min before kainic acid, had no effects on all parameters, tested in brain. In addition, the neuropeptides did not change the antioxidant status in brain of control animals. It might be concluded that N/OFQ(1-13)NH(2) and [Orn(9)]N/OFQ(1-13)NH(2) have neither pro- nor anti-oxidant activity.

Effect of copper intoxication on rat liver proteasome activity: relationship with oxidative stress.

Copper toxicity is associated with formation of reactive oxygen species, which are capable to oxidize proteins. The selective removal of the latter by the 20S proteasome is considered an essential part of the cell antioxidant defense system. The aim of the present study was to investigate whether peptidase activities of rat liver proteasomes were affected by chronic (40 mg CuSO(4)/rat/daily with the drinking water for 2 weeks) and acute (20 mg/kg CuSO(4), s.c.) copper treatment. To evaluate the role of proteasome, its inhibitor MG132 was also used. The degree of copper-induced oxidative stress (OS), established by measuring lipid peroxidation, protein oxidation, and cellular glutathione level, as well as activities of antioxidant enzymes--catalase, superoxide dismutase, and gultathionine peroxidase, depended on the mode of copper administration. Chronic copper administration (mild oxidative stress) did not affect proteasome activities, whereas acute copper treatment (severe oxidative stress) caused a decline in chymotryptic- and tryptic-like activities. The treatment of copper-loaded animals with MG132 did not change copper-induced alterations in the tested indices, except an additional increase in protein oxidation and inhibition of glutathionine peroxidase activity. The results suggested that the in vivo copper-induced oxidative stress was associated with changes in the catalytic activity of proteasome.

Effect of MG132 on proteasome activity and prooxidant/antioxidant status of rat liver subjected to ischemia/reperfusion injury.

AIM: Previous studies have shown that proteasome inhibitors exerted protective effects against ischemia/reperfusion injury (IRI) of brain, heart, kidney and intestine. The aim of the present study was to investigate: (i) whether the proteasome inhibitor MG132 protects rat liver against IRI; and (ii) whether MG132 modulates prooxidant/antioxidant status of rat liver subjected to warm IRI. METHODS: The left lateral and medial lobes (approximately 70% of the total liver volume) of livers of male Wistar rats were subjected to 30-min ischemia followed by 60-min reperfusion. Lactate dehydrogenase (LDH), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) levels were measured in the plasma. Proteasome chymotryptic-like (ChT-L) activity, levels of thiobarbituric acid-reactive substances (TBARS), protein carbonyls (PC) and glutathione (GSH), as well as superoxidase dismutase (SOD), catalase (CAT), glutathionine peroxidase and glutathionine reductase activities were measured in liver fractions. RESULTS: Thirty-min ischemia followed by 60-min reperfusion increased liver TBARS and PC, CAT and SOD activities, but decreased GSH level. Ischemia/reperfusion-induced oxidative stress was exacerbated in mitochondria, indicating that these organelles are the preferential target of IRI. Plasma LDH and AST levels were decreased by MG132 during both ischemia and reperfusion, while ALT values were decreased only after 30 min of reperfusion. MG132 did not significantly affect liver TBARS and GSH levels, but it increased PC and decreased ChT-L activity; the activities of CAT and SOD were also decreased. CONCLUSIONS: MG132 exerts a protective effect during the early phase of reperfusion and it modulates prooxidant/antioxidant status of rat liver subjected to warm IRI.