Cristiane Luchese

Brain and lungs of rats are differently affected by cigarette smoke exposure: Antioxidant effect of an organoselenium compound

Cigarette smoke exposure has been associated with oxidative stress in several organs. Antioxidant effect of diphenyl diselenide (PhSe)(2), an organoselenium compound, on oxidative damage induced by sub-chronic cigarette smoke exposure in brain and lungs of rats was investigated. Animals were exposed 5 times/week to one, two, three and four cigarettes for exposure periods of 15 min during the first, second, third and fourth weeks. Reactive species (RS) levels, enzymatic antioxidant defenses (superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR) and glutathione S-transferase (GST) activities) and non-enzymatic antioxidant defenses (ascorbic acid and non-protein thiol (NPSH) levels) were examined in brain and lungs of rats. An increase in RS levels induced by cigarette smoke in both tissues of rats was demonstrated. Cigarette smoke altered enzymatic antioxidant defenses (GST, CAT and SOD activities) in both tissues, and reduced the non-enzymatic antioxidant defenses in lungs. (PhSe)(2) (0.5 mg/kg/day, 5 times/week) restored RS levels and antioxidant defenses in brain of rats exposed to cigarette smoke. (PhSe)(2) treatment increased NPSH levels, GST and GR activities per se in lungs of rats. In conclusion, sub-chronic exposure to cigarette smoke caused alterations in antioxidant defense system and a tissue-specific oxidative stress in brain and lungs of rats. (PhSe)(2) restored antioxidant defenses in lungs and brain of rats.

Antioxidant effect of diphenyl diselenide on oxidative damage induced by smoke in rats: involvement of glutathione.

In the present study, the involvement of glutathione system in the restorative effect of diphenyl diselenide (PhSe)(2) on damage induced by cigarette smoke was investigated. Rat pups were progressively exposed to four, five, and six cigarettes for exposure periods of 15 min during their first, second, and third weeks of life. Thiobarbituric acid reactive species (TBARS) levels, components of the enzymatic antioxidant defenses (superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx), glutathione reductase (GR) and glutathione S-transferase (GST) activities), and non-enzymatic antioxidant defenses (vitamin C and non-protein thiol (NPSH) levels) were examined in lungs of pups. The results demonstrated an increase in lipid peroxidation and the alteration in non-enzymatic and enzymatic antioxidant defenses induced by cigarette smoke exposure in lung of pups. Administration of (PhSe)(2) (0.5mg/kg) restored TBARS levels and antioxidant defenses in lungs of rat pups exposed to cigarette smoke. (PhSe)(2) treatment increased NPSH levels and GST activity per se in lungs of rat pups. Together these results indicate that (PhSe)(2) restored oxidative damage induced by cigarette smoke exposure in lungs of rat pups. The glutathione system is involved in antioxidant effect of this compound.

Antioxidant effect of diphenyl diselenide on oxidative stress caused by acute physical exercise in skeletal muscle and lungs of mice

This study was designed to examine if diphenyl diselenide (PhSe)2, an organoselenium compound, attenuates oxidative stress caused by acute physical exercise in skeletal muscle and lungs of mice. Swiss mice were pre‐treated with (PhSe)2 (5u2009mgu2009kg‐1u2009day‐1) for 7 days. At the 7th day, the animals were submitted to acute physical exercise which consisted of continuous swimming for 20u2009min. The animals were euthanized 1 and 24u2009h after the exercise test. The levels of thiobarbituric acid reactive species (TBARS), non‐protein thiols (NPSH) and ascorbic acid and the activity of catalase (CAT) were measured in the lungs and skeletal muscle of mice. Glycogen content was determined in the skeletal muscle of mice. Parameters in plasma (urea and creatinine) were determined. The results demonstrated an increase in TBARS levels induced by acute physical exercise in the skeletal muscle and lungs of mice. Animals submitted to exercise showed an increase in non‐enzymatic antioxidant defenses (NPSH and ascorbic acid) in the skeletal muscle. In lungs of mice, activity of CAT was increased. (PhSe)2 protected against the increase in TBARS levels and ameliorated antioxidant defenses in the skeletal muscle and lungs of mice submitted to physical exercise. These results indicate that acute physical exercise caused a tissue‐specific oxidative stress in the skeletal muscle and lungs of mice. (PhSe)2 protected against oxidative damage induced by acute physical exercise in mice. Copyright

Sub-chronical exposure to diphenyl diselenide enhances acquisition and retention of spatial memory in rats

The present study was conducted to evaluate the effects of exposure to diphenyl diselenide [(PhSe)2] on cognitive performance and glutamatergic parameters in normal Wistar rats. Animals were subcutaneously exposed to (PhSe)2 acutely (G1) and sub-chronically for 4 weeks (G20) at the dose of 5.0 mg/kg or 8 weeks (G40) at the dose of 2.5 mg/kg and evaluated for behavioral and neurochemical analyses. In the water-maze, a significant increase in the number of crossing in the platform local was observed in the probe trial for both groups exposed to (PhSe)2 (G20 and G40). In the T-maze, the latency to reach the extremity of the arm in the trial 2 was lower in both groups exposed to (PhSe)2 (G20 or G40) when compared to the respective control groups. In the open-field test, no significant differences in the number of crossing and rearing were observed among groups. Furthermore, the basal [3H]glutamate release by synaptosomes from whole brain of rats was significantly decreased in the G40 when compared to the control group. These findings suggest that sub-chronic exposure to (PhSe)2 improved the performance of Wistar rats in the water-maze, a test that evaluates cognitive functions.

Antidepressant-like effect of diphenyl diselenide on rats exposed to malathion: involvement of Na+K+ ATPase activity.

The antidepressant-like effect of repeated administration of diphenyl diselenide (PhSe)2 in rats exposed to malathion is reported. The role of Na+K+ ATPase, acetylcholinesterase (AChE) and monoamine oxidase (MAO) activities and oxidative stress in antidepressant behavior were investigated in cerebral cortex of rats. Rats were exposed once a day for 3 consecutive days to malathion (50mg/kg, intraperitoneal) and (PhSe)2 (50mg/kg, oral). To investigate the antidepressant-like behavior rats were submitted to the forced swimming test (FST) and open-field test (OFT). Thiobarbituric acid reactive species (TBARS) levels, enzymatic and non-enzymatic antioxidant defenses were carried out in cerebral cortex of rats. The results confirmed that malathion increased immobility time in the FST without altering the locomotor performance in the OFT. Treatment with (PhSe)2 ameliorated performance in the FST without altering the crossing numbers in the OFT. The inhibition of Na+K+ ATPase activity caused by malathion was prevented by treatment with (PhSe)2. Exposure to malathion did not alter parameters of oxidative stress as well as AChE and MAO activities in cerebral cortex of rats. In conclusion, (PhSe)2 exerted antidepressant-like effect in rats exposed to malathion. Na+K+ ATPase activity is, at least in part, involved in (PhSe)2 antidepressant-like behavior.

Protective Effect of Diphenyl Diselenide on Ischemia and Reperfusion-Induced Cerebral Injury: Involvement of Oxidative Stress and Pro-Inflammatory Cytokines

Cerebrovascular diseases, including ischemic stroke, are associated with high mortality worldwide. Oxidative stress and inflammation are important pathophysiological mechanisms involved in post-ischemic cerebral injury. The present study was designed to investigate the potential protective effect of diphenyl diselenide (PhSe)2, an organoselenium compound with antioxidant and anti-inflammatory properties, against ischemia/reperfusion (I/R) insult in rat brain. The experimental model adopted was that of surgically-induced brain ischemia, performed by means of bilateral common carotid artery occlusion in rats. The effect of a single oral dose of (PhSe)2 (50xa0mg/kg), administered 30xa0min before the onset of ischemia, was investigated by assessing cerebral oxidative stress-related biochemical parameters and pro-inflammatory cytokines in plasma of rats. The results demonstrated an increase in the levels of malondialdehyde (MDA), reactive oxygen species (ROS) and nitrate/nitrite as well as the alteration in the non-enzymatic and enzymatic (catalase and superoxide dismutase) antioxidant defense system induced by I/R insult in rat brain. I/R insult increased the levels of IL-1β, IL-6, TNF-α and INF-γ in plasma of rats. The administration of (PhSe)2 restored cerebral levels of MDA, ROS, nitrate/nitrite and antioxidant defenses of rats exposed to I/R insult. (PhSe)2 markedly reduced pro-inflammatory cytokines in plasma of I/R rats. I/R insult increased the plasma levels of tissue damage markers, such as creatine kinase and α-1-acid glycoprotein. Pretreatment with (PhSe)2 was effective in reducing the levels of these proteins. In addition, (PhSe)2 attenuated cerebral histological alterations induced by I/R. This study showed for the first time the in vivo protective effect of (PhSe)2 against oxidative stress and pro-inflammatory cytokines-induced by I/R insult in rats.

Antioxidant effect of a novel class of telluroacetilene compounds: studies in vitro and in vivo.

AIMSnThe effect of telluroacetylenes a-d on pharmacological assays was investigated in vitro. A second objective of this study was to investigate the antioxidant action of compound b against the oxidative damage induced by sodium nitroprusside (SNP) in mouse brain.nnnMAIN METHODSnIn in vitro experiments, lipid peroxidation (LP) and protein carbonyl (PC) levels and delta-aminolevulinate dehydratase (delta-ALA-D) activity were carried out in rat brain homogenate. The thiol peroxidase-like activity and DPPH radical scavenging of telluroacetylenes a-d were investigated. In in vivo experiments, mice received SNP (0.335 micromol per site) intra cerebroventricular (i.c.v.) thirty minutes after oral administration of telluroacetylene b (10 mg/kg). After 1 h, animals were euthanized. The levels of LP and delta-ALA-D, catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR), glutathione S-transferase (GST) activities were carried out in mouse brain homogenate.nnnKEY FINDINGSnTelluroacetylenes a-d, at low muM range, reduced LP and PC levels in rat brain homogenate. Telluroacetylenes a-d showed effect of scavenging DPPH radicals. delta-ALA-D activity was inhibited by telloruacetylenes a-d, at high muM range, in rat brain homogenate. Brains of mice treated with SNP showed an increase in LP and the reduction in delta-ALA-D, GR and GST activities. Telluroacetylene b protected against the oxidative stress caused by SNP in brain of rats.nnnSIGNIFICANCEnThe results support an antioxidant effect of telluroacetylenes a-d in vitro. Telluroacetylene b protected against oxidative damage caused by SNP in mouse brain, suggesting an antioxidant effect of this compound.

Protective effect of meloxicam-loaded nanocapsules against amyloid-β peptide-induced damage in mice

The objective of present study was to investigate the protective effect of M-NC against aβ (25-35) peptide-induced damage in mice, as the first step to evaluate their potential value for the treatment of AD. Moreover, we compared the effects of M-NC with free meloxicam (M-F). Mice were divided into six groups: (I) sham, (II) aβ, (III) M-NC, (IV) M-F, (V) M-NC+aβ and (VI) M-F+aβ. Mice were pre-treated with M-NC (5mg/kg, by gavage), M-F (5mg/kg, by gavage) or blank nanocapsules (B-NC). Thirty minutes after treatments, aβ peptide (3nmol) or filtered water were i.c.v. injected. Learning and memory were assessed with the Morris water maze (MWM) (days 4-7) and step-down-type passive-avoidance (SDPA) (days 7-8) tasks. At the end of the experimental protocol (day 8), animals were euthanized and brains were removed for biochemical determinations (reactive species (RS), non-protein thiols (NPSH), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR), glutathione S-transferase (GST)) and histological examination. Our results confirmed that aβ peptide caused learning and memory deficits in mice. Histological analysis demonstrated neuronal loss, intense cellular accumulation and chromatolysis caused by aβ peptide. Furthermore, this study showed that oxidative stress was increased in mice that received aβ peptide. An important finding of the present study was the protective effect of M-NC in damage induced by aβ peptide. However, M-F did not have protective effect. In summary, the data reported herein clearly demonstrate that meloxicam carried by polymeric nanocapsules protected against learning and memory impairments, loss neuronal and oxidative stress in a mouse model of AD induced by aβ peptide.

Diphenyl diselenide ameliorates behavioral and oxidative parameters in an animal model of mania induced by ouabain.

Bipolar disorder (BD) is a common and severe mood disorder associated with higher rates of suicide and disability. Ouabain, a Na(+)/K(+)-ATPase inhibitor, induces behavioral changes in rats and has been used as a model of mania. The aim of this study was to investigate if diphenyl diselenide [(PhSe)(2)], an organoselenium compound with pharmacological properties, is effective against ouabain-induced hyperactivity and alterations in cerebral oxidative status of rats. Male Wistar rats were treated with a single dose of (PhSe)(2) (50 mg/kg, p.o.) 30 min before i.c.v. injection of ouabain (5 μl, 10(-5) M) or with the mood stabilizer, lithium chloride (LiCl) (45 mg/kg, p.o.), twice a day, for 7 days before the administration of ouabain. Open-field locomotion was quantified after ouabain administration. Thiobarbituric acid reactive substances (TBARS), oxidatively modified proteins, tyrosine nitration, ascorbic acid and non-protein thiols (NPSH) levels and superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione reductase (GR) activities were determined in the whole brain. Ouabain increased locomotor activity in the open-field test and pretreatment with (PhSe)(2) or LiCl blocked this effect. In addition, ouabain increased lipid peroxidation and oxidatively modified proteins, demonstrated by a significant increase in TBARS levels and carbonyl content, which were attenuated by pretreatment with (PhSe)(2) or LiCl. The activities of SOD and CAT were increased by ouabain. LiCl was effective on preventing the increases of both enzyme activities, but (PhSe)(2) attenuated the ouabain effect in SOD activity. GPx and GR activities, ascorbic acid, NPSH and tyrosine nitration levels were not altered in all experimental groups. Similarly to LiCl, (PhSe)(2) produced an antimanic-like action, since it was effective against the locomotor hyperactivity elicited by ouabain. The results also indicated that (PhSe)(2) was effective against oxidative stress caused by ouabain in rats.

Diphenyl diselenide in its selenol form has dehydroascorbate reductase and glutathione S‐transferase‐like activity dependent on the glutathione content

Objectivesu2002 The antioxidant action of diphenyl diselenide ((PhSe)2) is attributed to the mechanism by which (PhSe)2 has pharmacological activity. Although (PhSe)2 has glutathione peroxidase mimetic activity, the exact mechanism involved in its antioxidant effect has not yet been completely elucidated. In the present study, mechanisms involved in the antioxidant property of (PhSe)2 (1–50u2003µm) were investigated.