Prospecting for a quinoline containing selenium for comorbidities depression and memory impairment induced by restriction stress in mice.

RATIONALE: Depression is often associated with memory impairment, a clinical feature of Alzheimer's disease (AD), but no effective treatment is available. 7-Chloro-4-(phenylselanyl) quinoline (4-PSQ) has been studied in experimental models of diseases that affect the central nervous system. OBJECTIVES: The pharmacological activity of 4-PSQ in depressive-like behavior associated with memory impairment induced by acute restraint stress (ARS) in male Swiss mice was evaluated. METHODS: ARS is an unavoidable stress model that was applied for a period of 240 min. Ten minutes after ARS, animals were intragastrically treated with canola oil (10 ml/kg) or 4-PSQ (10 mg/kg) or positive controls (paroxetine or donepezil) (10 mg/kg). Then, after 30 min, mice were submitted to behavioral tests. Corticosterone levels were evaluated in plasma and oxidative stress parameters; monoamine oxidase (MAO)-A and MAO -B isoform activity; mRNA expression levels of kappa nuclear factor B (NF-κB); interleukin (IL)-1ß, IL-18, and IL-33; phosphatidylinositol-se-kinase (PI3K); protein kinase B (AKT2), as well as acetylcholinesterase activity were evaluated in the prefrontal cortex and hippocampus. RESULTS: 4-PSQ attenuated the depressive-like behavior, self-care, and memory impairment caused by ARS. Based on the evidence, we believe that effects of 4-PSQ may be associated, at least in part, with the attenuation of HPA axis activation, attenuation of alterations in the monoaminergic system, modulation of oxidative stress, reestablishment of AChE activity, modulation of the PI3K/AKT2 pathway, and reduction of neuroinflammation. CONCLUSIONS: These results suggested that 4-PSQ exhibited an antidepressant-like effect and attenuated the memory impairment induced by ARS, and it is a promising molecule to treat these comorbidities.

Amnesia-ameliorative effect of a quinoline derivative through regulation of oxidative/cholinergic systems and Na+/K+-ATPase activity in mice.

The present study evaluated the anti-amnesic activity of 1-(7-chloroquinolin-4-yl)-5-methyl-N-phenyl-1H-1,2,3-triazole-4-carboxamide (QTCA-1) against scopolamine (SCO)-induced amnesia in mice. It was evaluated cholinergic dysfunction, oxidative stress and Na+/K+-ATPase activity in cerebral cortex and hippocampus of mice. Male Swiss mice were treated with QTCA-1 (10 mg/kg, intragastrically (i.g.), daily) for nine days. Thirty minutes after the treatment with compound, the animals received a injection of SCO (0.4 mg/kg, intraperitoneally (i.p.)). Mice were submitted to the behavioral tasks 30 min after injection of SCO (Barnes maze, open-field, object recognition and location, and step-down inhibitory avoidance tasks) during nine days. In day 9, cerebral cortex and hippocampus of mice were removed to determine the thiobarbituric acid reactive species (TBARS) levels, and catalase (CAT), Na+/K+-ATPase and acetylcholinesterase (AChE) activities. SCO caused amnesia in mice for changing in step-down inhibitory avoidance, Barnes maze, and object recognition and object location tasks. QTCA-1 treatment attenuated the behavioral changes caused by SCO. Moreover, SCO increased AChE and CAT activities, decreased Na+/K+-ATPase activity and increased TBARS levels in the cerebral structures of mice. QTCA-1 protected against these brain changes. In conclusion, QTCA-1 had anti-amnesic action in the experimental model used in the present study, through the anticholinesterase effect, modulation of Na+/K+-ATPase activity and antioxidant action.

Modulation of COX-2, INF-É£, glutamatergic and opioid systems contributes to antinociceptive, anti-inflammatory and anti-hyperalgesic effects of bis(3-amino-2-pyridine) diselenide.

Preclinical assays play a key role in research in research on the neurobiology of pain and the development of novel analgesics. Drugs available for the treatment of inflammatory pain are not fully effective and show adverse effects. Thus, we investigated the antinociceptive, anti-inflammatory and anti-hyperalgesic effects of bis(3-amino-2-pyridine) diselenide (BAPD), a new analgesic drug prototype. BAPD effects were investigated using nociception models induced by chemical (glutamate), immunologic (Freund's Complete Adjuvant - CFA) and thermal stimuli in Swiss mice. Mice were orally (p.o.) treated with BAPD (0.1-50 mg/kg) 30 min prior to the glutamate and hot-plate tests and a time-course (0.5 up to 8 h) of the antinociceptive effect of BAPD (50 mg/kg, p. o.) was evaluated in a CFA model. In the CFA model, BAPD effects on cyclooxygenase-2 (COX-2), tumor necrosis factor (TNFα) and interferon-γ (INF-γ) expression, myeloperoxidase (MPO) activity, oxidative (2,2'-Azino-bis-3-ethylbenzothiazoline 6-sulfonic acid and 2,2-diphe- nyl-1-picrylhydrazyl levels) and histological parameters were evaluated. The safety of the compound (50 and 300 mg/kg, p. o.) was verified for 72 h. BAPD reduced the licking time induced by glutamate and caused an increase in latency response to thermal stimulus. Naloxone reversed the antinociceptive effect of BAPD. Paw edema formation induced by glutamate or CFA injection was reduced by BAPD. Mechanical hyperalgesia induced by CFA was attenuated by BAPD. BAPD did not protect against the increase in MPO activity and decrease of the 2,2'-Azino-bis-3-ethylbenzothiazoline 6-sulfonic acid and 2,2-diphe- nyl-1-picrylhydrazyl levels induced by CFA. BAPD protected against histological alterations and reduction on the levels of gene expression COX-2 and INF-γ in the paw of mice exposed to CFA. BAPD was safe at the doses and time evaluated. BAPD exerts acute antinociceptive, anti-inflammatory and anti-hyperalgesic actions, suggesting that it may represent an alternative in the future development of new therapeutic strategies.

Contribution of serotonergic and nitrergic pathways, as well as monoamine oxidase-a and Na+, K+-ATPase enzymes in antidepressant-like action of ((4-tert-butylcyclohexylidene) methyl) (4-methoxystyryl) sulfide (BMMS).

The present study investigated a possible antidepressant-like effect of ((4-tert-butylcyclohexylidene)methyl) (4-methoxystyryl) sulfide (BMMS) by using the forced swimming test (FST) and the tail suspension test (TST) in Swiss mice. The contribution of serotoninergic, glutamatergic and nitrergic systems in the antidepressant-like activity of BMMS was evaluated. We also examined the involvement of monoamine oxidase (MAO)-A, MAO-B and Na+, K+-ATPase activities in prefrontal cortex of mice. BMMS, (0.1-10 mg/kg, intragastrically (i.g.)) and fluoxetine (32 mg/kg, i.g.) decreased the immobility time in the FST and TST. The anti-immobility effect of BMMS (10 mg/kg, i.g.) in the TST was prevented by the pretreatment of mice with WAY100635 (0.1 mg/kg, subcutaneously (s.c.), a 5-HT1A receptor antagonist), ketanserin (5 mg/kg, intraperitoneal (i.p.), a 5-HT2A/2C receptor antagonist), and partially blocked by ondansetron (1 mg/kg, i.p., a 5-HT3 receptor antagonist). The anti-immobility effect of BMMS (10 mg / kg, i.g.) was not avoided by pretreatment with MK-801 (0.01 mg/kg, s.c. a non-competitive N-methyl D-Aspartate (NMDA) receptor) in the TST. Pretreatment with L-arginine (500 mg/kg, i.p., a nitric oxide precursor) reversed partially the reduction in the immobility time elicited by BMMS (10 mg/kg, i.g.) in TST. BMMS altered Na+,K+-ATPase and MAO-A activities in prefrontal cortex of mice, but was not able to change the MAO-B activity. In conclusion, BMMS exerted an antidepressant-like effect in mice and serotonergic and nitrergic systems are involved in the antidepressant-like action of compound. BMMS modulated MAO-A and Na+, K+- ATPase activities in prefrontal cortex of mice.

Post-mortem interval estimative through determination of catalase and Δ-aminolevulinate dehydratase activities in hepatic, renal, skeletal muscle and cerebral tissues of Swiss mice.

Purpose: Determining the post-mortem interval (PMI) is one of the challenging tasks in forensic science due to the lack of quick and inexpensive methods. Our objective is to develop innovative and alternative means for PMI evaluation. Methods: The relationship between PMI and enzymatic modifications in mice tissues was described. After being sacrificed, Swiss mice were randomly divided into groups according to the time elapsed since death. The activities of catalase (CAT) and δ-aminolevulinate dehydratase (δ-ALA-D) were determined in hepatic, renal, skeletal muscle and cerebral tissues. Results: CAT activity increased in kidney and brain 6 h after death and this increase remained for up to 24 h in the brain and 48 h in the kidney. δ-ALA-D had its activity decreased in the liver and kidneys in 6 h. In the skeletal muscle, δ-ALA-D activity was reduced only 48 h after death. Conversely, an increase on δ-ALA-D activity was observed in the brain at 6 h, followed by its decrease at 24 and 48 h. Conclusion: With the association of this set of results, it is possible to provide an estimate of PMI. Additionally, these results can be used as an auxiliary parameter associated with other methods to estimate PMI.

7-Chloro-4-(Phenylselanyl) Quinoline with Memory Enhancer Action in Aging Rats: Modulation of Neuroplasticity, Acetylcholinesterase Activity, and Cholesterol Levels.

This study investigated the effect of 7-chloro-4-(phenylselanyl) quinoline (4-PSQ) to restore the cognitive impairment caused by aging in male Wistar rats. Moreover, modulation of neuroplasticity markers, acetylcholinesterase (AChE) activity, and cholesterol levels was performed. Aged rats were intragastrically treated with 4-PSQ (5 mg/kg) for 7 days. Animals were tested in behavioral tasks, and then plasma (to determine cholesterol levels), hippocampus, and cerebral cortex (to determine neural cell adhesion molecule (NCAM) and polysialyltransferase (PST) levels, and AChE activity) were removed. Our findings demonstrated that treatment of aged rats with 4-PSQ restored short-term and long-term memories in the object recognition tests. 4-PSQ treatment did not restore exploratory activity (rearings) but partially restored locomotor activity (crossings) reduced by aging in the open-field test. Moreover, the compound restored the reduction in the NCAM and PST levels, and AChE activity in cerebral structures, as well as the increase in the plasma cholesterol levels, caused by aging in rats. In conclusion, 4-PSQ restored cognitive impairment caused by aging in rats by modulating synaptic plasticity, cholinergic system, and cholesterol levels.

Synthesis and Pharmacological Evaluation of Novel Selenoethers Glycerol Derivatives for the Treatment of Pain and Inflammation: Involvement of Nitrergic and Glutamatergic Systems.

In the present study, the synthesis of new selenoethers from nucleophilic substitution reaction between organyl halides and nucleophilic species of selenium generated in situ was demonstrated. After, this method was applied for the synthesis of pyridylselenides glycerol derivatives 9b and 9c and the antinociceptive and anti-inflammatory effects, as well as, acute toxicity were evaluated. In the formalin test, the compound 9b caused a reduction in licking time in both phases. Compounds 9b and 9c increased the latency to response in the hot-plate test and reduced the licking time induced by glutamate. Our results revealed the involvement of the nitrergic and/or glutamatergic pathways in the antinociceptive action of the compounds. Additionally, 9b and 9c did not cause any toxicity signals and oxidative stress parameters were not modified by treatments. Here, it was developed an alternative and efficient method for the synthesis of selenoethers glycerol derivatives. Furthermore, we demonstrated that this class is indeed interesting for the research of new drugs. Graphical Abstract ᅟ.

The efficacy of microemulsion-based delivery to improve vitamin E properties: evaluation of the antinociceptive, antioxidant, antidepressant- and anxiolytic-like activities in mice.

OBJECTIVES: A microemulsion-based delivery system was designed to improve vitamin E (VE) properties, and its antinociceptive, antioxidant, antidepressant- and anxiolytic-like activities in mice were evaluated. METHODS: Male Swiss mice received, by intragastric route, canola oil (20 ml/kg), blank microemulsion (B-ME) (20 ml/kg), VE free (VE-F) (200 mg/kg) or VE microemulsion (VE-ME) (200 mg/kg). In acute treatment, a single dose of treatments was administrated and 30 min after behavioural tests were performed. In the subchronic treatment, mice received such treatments, once a day, for 8 days. On the eighth day, behavioural tests were performed. KEY FINDINGS: In the subchronic treatment, VE-ME increased entries and spent time in the open arms in the elevated plus-maze test and decreased the immobility time in the tail suspension test, but no change was found after acute treatment. Acute and subchronic treatments with VE-ME increased response latency to thermal stimulus in the hot-plate test. VE-ME decreased the thiobarbituric acid reactive species levels in the acute and subchronic protocols. Additionally, in subchronic treatment, VE-ME increased renal catalase activity, but VE-F reduced its activity. CONCLUSIONS: Vitamin E-microemulsions showed antioxidant, antinociceptive, antidepressant- and anxiolytic-like actions; thus, ME-based delivery improved pharmacological properties of VE.

Current advances of pharmacological properties of 7-chloro-4-(phenylselanyl) quinoline: Prevention of cognitive deficit and anxiety in Alzheimer's disease model.

This study investigated the effect of 7-chloro-4-(phenylselanyl) quinoline (4-PSQ) at a dose of 1 mg/kg in memory impairment and anxiety in an Alzheimer's disease (AD) model induced by amyloid ß-peptide (Aß) (fragment 25-35) in mice. The involvement of acetylcholinesterase (AChE) activity and lipid peroxidation in hippocampus and cerebral cortex was evaluated. Male Swiss mice were pretreated with 4-PSQ (1 mg/kg, intragastrically (i.g.), daily) for fourteen days. Thirty minutes after the first treatment with 4-PSQ, the animals received a single injection of Aß (3 nmol/3 µl/per site, intracerebroventricular (i.c.v.)). Mice were submitted to the behavioral tasks (open-field, elevated plus maze, Barnes maze, object recognition and location, and step-down inhibitory avoidance tests) from the fifth day onwards. On the fifteenth day, blood was removed for analysis of biochemical markers (glucose, triglycerides, urea, aspartate (AST) and alanine (ALT) aminotrasferases), and cerebral cortex and hippocampus for determination of AChE activity and thiobarbituric acid reactive species (TBARS) levels. Aß caused memory impairment, anxiogenic behavior, increased AChE activity in the cerebral structures and TBARS levels in the cerebral cortex. 4-PSQ was effective to protect against behavioral changes, AChE activity and TBARS levels. In conclusion, 4-PSQ protected against learning and memory impairment and anxiety in a mouse model of AD induced by Aß, and anticholinesterase and antioxidant actions are involved in the pharmacological effect of the compound.

7-Chloro-4-phenylsulfonyl quinoline, a new antinociceptive and anti-inflammatory molecule: Structural improvement of a quinoline derivate with pharmacological activity.

The present study was designed to examine the antinociceptive and anti-inflammatory effects of 7-chloro-4-phenylsulfonyl quinoline (PSOQ). Mice were orally (p.o) pretreated with PSOQ (0.01-10 mg/kg), meloxicam (10 mg/kg), 30 min prior to the acetic acid, hot-plate and open field tests. PSOQ reduced abdominal writhing induced by acetic acid, while meloxicam presented no effect. The latency time in the hot-plate test and locomotor/exploratory activities in the open field test were not altered by treatments. In order to evaluate the gastric tolerability after oral administration of PSOQ or meloxicam (10 mg/kg), mice were fasted for 18 h prior to drug exposure. Four hours later, the development of lesions was assessed. PSOQ and meloxicam did not induce ulcer at the dose and time evaluated. Indeed, anti-inflammatory and anti-edematogenic properties of PSOQ were investigated. For this, animals were pretreated with PSOQ (0.01-50 mg/kg; p.o.), meloxicam (50 mg/kg; p.o.), 30 min prior to croton oil application. PSOQ and meloxicam (50 mg/kg) diminished the edema formation and myeloperoxidase activity induced by croton oil in the ear tissue. Taken together these data demonstrated that PSOQ exerts acute anti-inflammatory and antinociceptive actions, suggesting that it may represent an alternative in the development of future new therapeutic strategies.

Selective A2A receptor antagonist SCH 58261 modulates striatal oxidative stress and alleviates toxicity induced by 3-Nitropropionic acid in male Wistar rats.

The aim of the present study was to investigate the effects of SCH58261, a selective adenosine A2A receptor antagonist, on striatal toxicity induced by 3-nitropropionic acid (3-NP) in rats. The experimental protocol consisted of 10 administrations (once a day) of SCH58261 (0.01 or 0.05 mg/kg/day, intraperitoneal, i.p.). From 7th to 10th day, 3-NP (20 mg/kg/day, i.p.) was injected 1 h after SCH58261 administration. Twenty-four hours after the last 3-NP injection, the body weight gain, locomotor activity (open-field test), motor coordination (rotarod test), striatal succinate dehydrogenase (SDH) activity and parameters linked to striatal oxidative status were evaluated in rats. The marked body weight loss resulting from 3-NP injections in rats was partially protected by SCH 58261 at both doses. SCH 58261 at the highest dose was effective against impairments on motor coordination and locomotor activity induced by 3-NP. SCH 58261 was unable to restore the inhibition of SDH activity caused by 3-NP. In addition, the increase in striatal reactive species (RS) levels, depletion of reduced glutathione (GSH) content and stimulation of glutathione reductase (GR) activity provoked by 3-NP injections were alleviated by both doses of SCH 58261. The highest dose of SCH 58261 was also effective in attenuating the increase of protein carbonyl levels as well as the inhibition of glutathione peroxidase (GPx) activity in rats exposed to 3-NP. Our results revealed that reduction of oxidative stress in rat striatum by adenosine A2A receptor antagonism contributes for alleviating 3-NP-induced toxicity.

Organosulfur compound protects against memory decline induced by scopolamine through modulation of oxidative stress and Na+/K+ ATPase activity in mice.

The present study investigated the possible effect of BMMS in protecting against memory impairment in an Alzheimer's disease model induced by scopolamine in mice. Another objective was to evaluate the involvement of oxidative stress and Na+/K+ ATPase activity in cerebral cortex and hippocampus of mice. Male Swiss mice were divided into four groups: groups I and III received canola oil (10 ml/kg, intragastrically (i.g.)), while groups II and IV received BMMS (10 mg/kg, i.g.). Thirty minutes after treatments, groups III and IV received scopolamine (1 mg/kg, intraperitoneal (i.p.)), while groups I and II received saline (5 ml/kg, i.p.). Behavioral tests were performed thirty minutes after scopolamine or saline injection. Cerebral cortex and hippocampus were removed to determine the thiobarbituric acid reactive species (TBARS) levels, non-protein thiols (NPSH) content, catalase (CAT) and Na+/K+ ATPase activities. The results showed that BMMS pretreatment protected against the reduction in alternation and latency time induced by scopolamine in the Y-maze test and step-down inhibitory avoidance, respectively. In the Barnes maze, the latency to find the escape box and the number of holes visited were attenuated by BMMS. Locomotor and exploratory activities were similar in all groups. BMMS pretreatment protected against the increase in the TBARS levels, NPSH content and CAT activity, as well as the inhibition on the Na+/K+ ATPase activity caused by scopolamine in the cerebral cortex. In the hippocampus, no significant difference was observed. In conclusion, the present study revealed that BMMS protected against the impairment of retrieval of short-term and long-term memories caused by scopolamine in mice. Moreover, antioxidant effect and protection on the Na+/K+ ATPase activity are involved in the effect of compound against memory impairment in AD model induced by scopolamine.

Antioxidant compound (E)-2-benzylidene-4-phenyl-1,3-diselenole protects rats against thioacetamide-induced acute hepatotoxicity.

The aim of this study was to investigate whether (E)-2-benzylidene-4-phenyl-1,3-diselenole (BPD) protects against hepatotoxicity induced by thioacetamide (TAA). On the first day of treatment, male adult Wistar rats received BPD (10 or 50 mg·kg-1). On the second day, the rats received a single intraperitoneal injection of TAA (400 mg·kg-1). Twenty-four hours after TAA administration, biochemical determinations and liver histological analysis were carried out. BPD (50 mg·kg-1) reduced plasma aspartate and alanine aminotransferase, alkaline phosphatase, and lactate dehydrogenase activities increased by TAA exposure. Treatment with BPD was effective against increased lipid peroxidation levels and attenuated a decrease in hepatic reduced glutathione and ascorbic acid levels as well as an inhibition of glutathione peroxidase activity caused by TAA exposure. The higher dose of BPD protected against the inhibition of hepatic δ-aminolevulinic dehydratase activity induced by TAA. Finally, histopathological examination of the liver showed that BPD markedly ameliorated TAA-induced hepatic injury. In conclusion, BPD protected against hepatotoxicity and oxidative stress caused by TAA exposure in rats.

Antioxidant effect of quinoline derivatives containing or not selenium: Relationship with antinociceptive action quinolines are antioxidant and antinociceptive.

The present study investigated the antioxidant effect of a new class of quinoline derivatives (a-d) on assays in vitro. Lipid peroxidation, thiol peroxidase-like and free radical scavenging activities were determined to evaluate antioxidant activity of compounds. Thiol oxidase-like and δ-aminolevulinate dehydratase activities were performed as a toxicological parameter. A second objective of this study was to evaluate the in vivo antinociceptive effect of the compound with better antioxidant effect and without toxic effects in a model of nociception induced by formalin in mice. In liver, at 100 µM, compound a reduced the lipid peroxidation to the control levels, while compounds c and d partially reduced it. In brain, only compound d partially reduced the lipid peroxidation at 50 and 100 µM. Compound b did not have an effect on the lipid peroxidation. Thiol peroxidase-like and free radical scavenging activities are not involved in the antioxidant mechanisms of these compounds. Compounds did not present thiol oxidase-like activity and effect on the δ-aminolevulinate dehydratase. In vivo experiments showed that compound a caused an inhibition of licking time in the first and second phases, and edema formation induced by formalin. In conclusion, quinoline derivative without selenium presented better in vitro antioxidant effect and in vivo antinociceptive activity.

Further analysis of acute antinociceptive and anti-inflammatory actions of 4-phenylselenyl-7-chloroquinoline in mice.

A new quinoline containing selenium, 4-phenylselenyl-7-chloroquinoline (4-PSQ), was described and synthetized by our research group. Recently, we demonstrated the potential antinociceptive and anti-inflammatory of 4-PSQ. For this reason, the first objective of this study was to expand our previous findings by investigating the contribution of glutamatergic, serotonergic, and nitrergic systems to the acute antinociceptive action of this compound. Pretreatment with 4-PSQ (0.01-25 mg/kg, p.o.) reduced the nociception induced by glutamate. MK-801 (an uncompetitive antagonist of the N-Methyl-d-aspartate (NMDA) receptor) blocked the antinociceptive effect exerted by 4-PSQ (25 mg/kg, p.o.) in the acetic acid-induced abdominal writhing test. The pretreatment with WAY100635 (a selective antagonist of 5-HT1A receptor), ketanserin (a selective antagonist of 5-HT2A/2C receptor), and pindolol (a nonselective antagonist of 5-HT1A/1B receptors) partially blocked the antinociceptive effect caused by 4-PSQ (25 mg/kg, per oral, p.o.) in the acetic acid-induced abdominal writhing test. Nitric oxide precursor, l-arginine hydrochloride, partially reversed antinociception caused by 4-PSQ or ω-nitro-l-arginine (l-NOARG). Treatments did not modify the locomotor and exploratory activities of mice. Additionally, the acute anti-inflammatory effect of 4-PSQ in a model of pleurisy induced by carrageenan in mice was investigated. 4-PSQ reduced the cellular migration, pleural exudate accumulation, and myeloperoxidase activity induced by carrageenan exposure. 4-PSQ protected against the increase in reactive species levels and reduction of nonprotein thiol levels induced by carrageenan. Data presented here showed that the modulation of serotonergic, nitrergic, and glutamatergic systems contributed to the antinociceptive effect of 4-PSQ and it reinforced the therapeutic potential of this quinolinic compound for acute inflammation.

Antioxidant effect of quinoline derivatives containing or not selenium: Relationship with antinociceptive action quinolines are antioxidant and antinociceptive

ABSTRACT The present study investigated the antioxidant effect of a new class of quinoline derivatives (a-d) on assays in vitro. Lipid peroxidation, thiol peroxidase-like and free radical scavenging activities were determined to evaluate antioxidant activity of compounds. Thiol oxidase-like and δ-aminolevulinate dehydratase activities were performed as a toxicological parameter. A second objective of this study was to evaluate the in vivo antinociceptive effect of the compound with better antioxidant effect and without toxic effects in a model of nociception induced by formalin in mice. In liver, at 100 µM, compound a reduced the lipid peroxidation to the control levels, while compounds c and d partially reduced it. In brain, only compound d partially reduced the lipid peroxidation at 50 and 100 µM. Compound b did not have an effect on the lipid peroxidation. Thiol peroxidase-like and free radical scavenging activities are not involved in the antioxidant mechanisms of these compounds. Compounds did not present thiol oxidase-like activity and effect on the δ-aminolevulinate dehydratase. In vivo experiments showed that compound a caused an inhibition of licking time in the first and second phases, and edema formation induced by formalin. In conclusion, quinoline derivative without selenium presented better in vitro antioxidant effect and in vivo antinociceptive activity.

Polymeric nanocapsules as a technological alternative to reduce the toxicity caused by meloxicam in mice.

This study determined whether meloxicam in nanocapsules modifies stomach and liver damage caused by free meloxicam in mice. Male Swiss mice were treated with blank nanocapsules or meloxicam in nanocapsules or free meloxicam (10 mg/kg, intragastrically, daily for five days). On the seventh day, blood was collected to determine biochemical markers (glutamic oxaloacetic transaminase, glutamic pyruvic transaminase, total bilirubin, unconjugated bilirubin, albumin and alkaline phosphatase). Stomachs and livers were removed for histological analysis. There was no significant difference in the biochemical markers in the plasma of mice. Meloxicam in nanocapsules did not have an ulcerogenic potential in the stomach or cause lipid peroxidation in the stomach and liver. Free meloxicam increased the ulcerogenic potential in the stomach and lipid peroxidation in the stomach and liver. Meloxicam in nanocapsules caused less histological changes than free meloxicam. In conclusion, polymeric nanocapsules can represent a technological alternative to reduce the toxicity caused by meloxicam.