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1.
Psychopharmacology (Berl) ; 238(7): 1937-1951, 2021 Jul.
Article in English | MEDLINE | ID: mdl-33740091

ABSTRACT

RATIONALE: Obesity is considered one of the major global health problems and increases the risk of several medical complications, such as diabetes and mental illnesses. OBJECTIVE: The present study investigated the effect of 7-chloro-4-(phenylselanyl) quinoline (4-PSQ) on obesity parameters, behavioral and neurochemical alterations in hypothalamic obese rats. METHODS: Male Wistar rats received subcutaneous neonatal injections of monosodium glutamate (MSG, 4g/kg) or saline. After the Lee Index evaluation, rats were divided into groups and treated with 4-PSQ (5 mg/kg, intragastric route) or canola oil once a day (post-natal days (PND) 60→76). Open-field, elevated plus-maze, forced swim task, object recognition/location memory, and stepdown inhibitory avoidance tasks were conducted from PND 66 to 74. On PND 76, rats were euthanized and epididymal fat, blood, cerebral cortex, andhippocampus were removed. Blood biochemical parameters and cortical/hippocampal acetylcholinesterase (AChE) and Na /K -ATPase activities were assessed. RESULTS: MSG increased the Lee Index characterizing the chemically induced hypothalamic obesity model. 4-PSQ reversed the increases of epididymal fat, blood glucose, and triglyceride levels caused by MSG exposure. 4-PSQ attenuated anxiety-like and depression-like behaviors induced by neonatal administrations of MSG. Memory deficits found in MSG-obese rats were reversed by treatment with 4-PSQ. Neurochemical alterations produced by MSG evidenced by stimulation ofNa+/K+-ATPase and AChE activities in the cerebral cortex and hippocampus of rats were normalized by 4-PSQ treatment. CONCLUSIONS: In brief, 4-PSQ therapy improved hypothalamic obesity-related parameters, as well as psychiatric symptoms, cognitive impairment, and neurochemical alterations found in obese rats.


Subject(s)
Hypothalamus/drug effects , Obesity/drug therapy , Obesity/psychology , Quinolines/administration & dosage , Selenium/administration & dosage , Animals , Hypothalamus/metabolism , Male , Maze Learning/drug effects , Maze Learning/physiology , Obesity/chemically induced , Obesity/metabolism , Rats , Rats, Wistar , Sodium Glutamate/toxicity
2.
An Acad Bras Cienc ; 92(2): e20191141, 2020.
Article in English | MEDLINE | ID: mdl-32813863

ABSTRACT

The aim of this study was to investigate the effects of yerba mate (Ilex paraguariensis St. Hil.) extract (YME) on oxidative stress parameters and pathological changes in the lungs of mice chronically exposed to hand-rolled cornhusk cigarette (HRC) smoke. Twenty-four male Swiss mice were divided into four groups exposed to the following treatments: control (ambient air), HRC, YME, and HRC plus YME. The animals were exposed to four HRCs per session, with 3 sessions/day, every day for 30 days. Twenty-four hours after the last inhalation, the mice were killed, and the left lungs were removed. The results showed that HRC contains elevated levels of tin and carbon oxide, but less arsenic, cobalt, manganese, and selenium than commercial cigarettes. YME administration reversed fibrosis, alveolar enlargement, and hemorrhage induced by HRC smoke. In addition, the YME and HRC significantly reduced the production of oxidants, oxidative damage and promoted a significant increase in total thiol. In conclusion, exposure to HRC smoke compromised pulmonary histoarchitecture by promoting structural changes and increasing oxidative stress in tissues. However, concomitant treatment with YME regulated the redox state and reduced the harmful effects of HRC smoke exposure in the lungs.


Subject(s)
Ilex paraguariensis , Animals , Male , Mice , Oxidation-Reduction , Oxidative Stress , Plant Extracts , Smoke , Smoking
3.
Biomed Pharmacother ; 105: 1006-1014, 2018 Sep.
Article in English | MEDLINE | ID: mdl-30021335

ABSTRACT

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.


Subject(s)
Alzheimer Disease/drug therapy , Amyloid beta-Peptides/toxicity , Anxiety/prevention & control , Cognitive Dysfunction/prevention & control , Disease Models, Animal , Peptide Fragments/toxicity , Quinolines/therapeutic use , Alzheimer Disease/chemically induced , Alzheimer Disease/metabolism , Animals , Anxiety/chemically induced , Anxiety/metabolism , Cognitive Dysfunction/chemically induced , Cognitive Dysfunction/metabolism , Locomotion/drug effects , Locomotion/physiology , Male , Maze Learning/drug effects , Maze Learning/physiology , Mice , Quinolines/pharmacology , Random Allocation
4.
Chem Biol Interact ; 282: 7-12, 2018 Feb 25.
Article in English | MEDLINE | ID: mdl-29317251

ABSTRACT

The quinolone compounds have been reported for many biological properties, especially as potent antioxidants. This study investigated the antioxidant effect of 7-chloro-4-phenylselenyl-quinoline (PSQ), a quinolone derivative with organoselenium group, against oxidative stress induced by sodium nitroprusside (SNP) in brains of mice. A second objective was to verify the importance of phenylselenyl group presents at position 4 of the quinoline structure to antioxidant effect of compound. So, it was compared the antioxidant effect of PSQ with a quinoline without organoseleniun group (7-chloroquinoline [QN]). Swiss mice were used and received SNP (0.335 µmol/site, intracerebroventricular) 30 min after treatment with PSQ or QN, at the doses of 50 mg/kg (intragastrically). After 1 h, animals were sacrificed and the brains were removed to biochemistry analysis. Thiobarbituric acid reactive species (TBARS), protein carbonyl (PC) and non-protein thiol (NPSH) levels, as well as catalase (CAT), glutathione S transferase (GST) and δ -aminolevulinic acid (δ-ALA-D) activities were determined. SNP increased TBARS and PC levels, and reduced the enzymatic (CAT and GST activity) and non-enzymatic (NPSH levels) antioxidant defenses and inhibited the δ-ALA-D activity. PSQ avoided the increase in the lipid peroxidation and PC levels, as well as the decrease in the NPSH levels, CAT, GST and δ-ALA-D activities QN partially avoided the increase in lipid peroxidation, but it not protected against alterations induced by SNP. In conclusion, phenylselenyl group present in quinoline structure is critical for antioxidant activity of PSQ.


Subject(s)
Antioxidants/pharmacology , Organoselenium Compounds/pharmacology , Quinolines/pharmacology , Aminolevulinic Acid/metabolism , Animals , Brain/drug effects , Brain/metabolism , Catalase/metabolism , Glutathione Peroxidase/metabolism , Glutathione Transferase/metabolism , Lipid Peroxidation/drug effects , Male , Mice , Oxidative Stress/drug effects , Sulfhydryl Compounds/metabolism , Thiobarbituric Acid Reactive Substances/metabolism
5.
Metab Brain Dis ; 32(6): 1819-1828, 2017 12.
Article in English | MEDLINE | ID: mdl-28710722

ABSTRACT

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.


Subject(s)
Antioxidants/pharmacology , Memory Disorders/drug therapy , Memory/drug effects , Oxidative Stress/drug effects , Sodium-Potassium-Exchanging ATPase/metabolism , Sulfides/pharmacology , Animals , Antioxidants/therapeutic use , Catalase/metabolism , Cerebral Cortex/drug effects , Cerebral Cortex/metabolism , Hippocampus/drug effects , Hippocampus/metabolism , Male , Memory Disorders/chemically induced , Memory Disorders/metabolism , Mice , Scopolamine , Sulfides/therapeutic use , Thiobarbituric Acid Reactive Substances/metabolism
6.
J Pharm Sci ; 105(7): 2194-203, 2016 07.
Article in English | MEDLINE | ID: mdl-27290627

ABSTRACT

Previous studies have demonstrated the antiherpes activity of pentyl gallate (PG), suggesting that it could be a promising candidate for the topical treatment of human herpes labialis. PG low aqueous solubility represents a major drawback to its incorporation in topical dosage forms. Hence, the feasibility of incorporating PG into nanoemulsions, the ability to penetrate the skin, to inhibit herpes simplex virus (HSV)-1 replication, and to cause dermal sensitization or toxicity were evaluated. Oil/water nanoemulsions containing 0.5% PG were prepared by spontaneous emulsification. The in vitro PG distribution into porcine ear skin after topical application of nanoemulsions was assessed, and the in vitro antiviral activity against HSV-1 replication was evaluated. Acute dermal toxicity and risk of dermal sensitization were evaluated in rat model. Nanoemulsions presented nanometric particle size (from 124.8 to 143.7 nm), high zeta potential (from -50.1 to -66.1 mV), loading efficiency above 99%, and adequate stability during 12 months. All formulations presented anti-HSV-1 activity. PG was able to reach deeper into the dermis more efficiently from the nanoemulsion F4. This formulation as well as PG were considered safe for topical use. Nanoemulsions seem to be a safe and effective approach for topically delivering PG in the treatment of human herpes labialis infection.


Subject(s)
Antiviral Agents/administration & dosage , Antiviral Agents/therapeutic use , Gallic Acid/analogs & derivatives , Herpes Labialis/drug therapy , Administration, Topical , Animals , Antiviral Agents/toxicity , Drug Stability , Emulsions , Gallic Acid/administration & dosage , Gallic Acid/therapeutic use , Gallic Acid/toxicity , Herpesvirus 1, Human/drug effects , Irritants , Male , Rats , Rats, Wistar , Skin Absorption , Skin Diseases/chemically induced , Skin Diseases/pathology , Solubility , Swine , Virus Replication/drug effects
7.
J Ethnopharmacol ; 153(3): 908-16, 2014 May 14.
Article in English | MEDLINE | ID: mdl-24704489

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: Scutia buxifolia is a native tree of Southern Brazil, Uruguay, and Argentina, which is popularly known as "coronilha" and it is used as a cardiotonic, antihypertensive and diuretic substance. The aim of this study was to assess the acute and sub-acute toxicity of the ethyl acetate fraction from the stem bark Scutia buxifolia in male and female mice. MATERIALS AND METHODS: The toxicity studies were based on the guidelines of the Organization for Economic Cooperation and Development (OECD-guidelines 423 and 407). In an acute study, a single dose of 2000 mg/kg of Scutia buxifolia was administered orally to male and female mice. Mortality, behavioral changes, and biochemical and hematological parameters were evaluated. In the sub-acute study, Scutia buxifolia was administered orally to male and female mice at doses of 100, 200, and 400mg/kg/day for 28 days. Behavioral changes and biochemical, hematological, and histological analysis were evaluated. RESULTS: The acute administration of Scutia buxifolia did not cause changes in behavior or mortality. Male and female mice presented decreased levels of platelets. Female mice presented decreased levels of leukocytes. On the other hand, in a sub-acute toxicity study, we observed no behavioral changes in male or female mice. Our results demonstrated a reduction in glucose levels in male mice treated to 200 and 400mg/kg of Scutia buxifolia. Aspartate aminotransferase (ASAT) activity was increased by Scutia buxifolia at 400mg/kg in male mice. In relation to the hematological parameters, male mice presented a reduction in hemoglobin (HGB) and hematocrit (HCT) when treated to 400mg/kg of plant fraction. Female mice showed no change in these parameters. Histopathological examination of liver tissue showed slight abnormalities that were consistent with the biochemical variations observed. CONCLUSION: Scutia buxifolia, after acute administration, may be classified as safe (category 5), according to the OECD guide. However, the alterations observed, after sub-acute administration with high doses of ethyl acetate fraction from the stem bark Scutia buxifolia, suggest that repeated administration of this fraction plant can cause adverse hepatic, renal, and hematological effects.


Subject(s)
Plant Extracts/toxicity , Rhamnaceae , Acetates/chemistry , Animals , Aspartate Aminotransferases/blood , Female , Hematocrit , Hemoglobins/analysis , Kidney/drug effects , Kidney/pathology , Liver/drug effects , Liver/pathology , Male , Mice , Plant Bark , Plant Stems , Solvents/chemistry , Toxicity Tests, Acute , Toxicity Tests, Subacute
8.
J Appl Toxicol ; 34(1): 87-94, 2014 Jan.
Article in English | MEDLINE | ID: mdl-23229315

ABSTRACT

The present study investigated the protective role of antioxidant (E)-2-benzylidene-4-phenyl-1,3-diselenole (BPD), an organoselenium compound, against the renal injury induced by cisplatin in rats. Canola oil or BPD (50 mg kg(-1)) was administered orally by gavage once a day for 6 days to rats. The first dose of BPD was given 24 h before a single intraperitoneal injection of saline or cisplatin (7 mg kg(-1)). At day 7, animals were killed and parameters related to renal injury were determined. The histological analysis showed that cisplatin caused renal injury in rats, which was accompanied by an increase in urea and creatinine levels in plasma. The increase of plasma creatinine levels negatively correlated with renal antioxidant defenses including ascorbic acid (AA) and reduced glutathione (GSH) content as well as glutathione S-transferase (GST), glutathione peroxidase (GPx) and catalase (CAT) activities. As revealed by histological analysis, BPD ameliorated tubular injury in rat kidney and reduced plasma markers altered by cisplatin. The administration of BPD to rats attenuated the reduction of renal AA and GSH content in animals exposed to cisplatin. The decrease of GST activity, but not GPx and CAT activities, in rats exposed to cisplatin was totally reversed by BPD administration. BPD was also effective in attenuating the inhibition of a sulfhydryl enzyme sensitive to oxidative stress, δ-aminolevulinic dehydratase, in kidneys of rats exposed to cisplatin. The present study demonstrated that BPD reduced renal injury induced by cisplatin in rats and this effect seems to be related to antioxidant mechanisms.


Subject(s)
Antioxidants/pharmacology , Cisplatin/adverse effects , Kidney/drug effects , Organoselenium Compounds/pharmacology , Acute Kidney Injury/chemically induced , Acute Kidney Injury/drug therapy , Animals , Ascorbic Acid/blood , Catalase/metabolism , Creatinine/blood , Glutathione/metabolism , Glutathione Peroxidase/metabolism , Glutathione Transferase/metabolism , Injections, Intraperitoneal , Male , Oxidative Stress/drug effects , Rats , Rats, Wistar
9.
Environ Toxicol Pharmacol ; 36(3): 750-8, 2013 Nov.
Article in English | MEDLINE | ID: mdl-23958967

ABSTRACT

This study aimed to investigate the beneficial effect of diphenyl diselenide (PhSe)2 on paraquat (PQ) induced alterations in rats liver. Adult male Wistar rats received (PhSe)2 at 10 mg kg(-1), by oral administration (p.o.), during five consecutive days. Twenty-four hours after the last (PhSe)2 dose, rats received PQ at 15 mg kg(-1), in a single intraperitoneally injection (i.p.). Seventy-two hours after PQ exposure, animals were sacrificed by decapitation for blood and liver samples obtainment. Histological alterations induced by PQ exposure, such as inflammatory cells infiltration and edema, were prevented by (PhSe)2 administration. Moreover, (PhSe)2 prevented hepatic lipid peroxidation (LPO) induced by PQ and was effective in reducing the myeloperoxidase (MPO) activity in liver, which was enhanced by PQ exposure. (PhSe)2 also was effective in protecting against the reduction in ascorbic acid and non-protein thiols (NPSH) levels induced by PQ. The inhibition of glutathione S-transferase (GST) activity, in rats exposed to PQ, was normalized by (PhSe)2 pre-treatment, whereas the inhibition of catalase (CAT) activity was not prevented by (PhSe)2. The serum alkaline phosphatase (ALP) inhibition, induced by PQ administration, was also prevented by (PhSe)2 pre-treatment. Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities were not modified by PQ and/or (PhSe)2 administration. Therefore, (PhSe)2 pre-treatment was effective in protecting against the hepatic alterations induced by PQ in rats. This protective effect can involve the antioxidant and anti-inflammatory properties of (PhSe)2.


Subject(s)
Benzene Derivatives/pharmacology , Chemical and Drug Induced Liver Injury/pathology , Chemical and Drug Induced Liver Injury/prevention & control , Herbicides/antagonists & inhibitors , Herbicides/toxicity , Organoselenium Compounds/pharmacology , Paraquat/antagonists & inhibitors , Paraquat/toxicity , Animals , Ascorbic Acid/metabolism , Catalase/metabolism , Glutathione Transferase/metabolism , Lipid Peroxidation/drug effects , Liver/pathology , Liver Function Tests , Male , Peroxidase/metabolism , Rats , Rats, Wistar , Sulfhydryl Compounds/metabolism
10.
Environ Toxicol Pharmacol ; 34(3): 985-94, 2012 Nov.
Article in English | MEDLINE | ID: mdl-22981437

ABSTRACT

The effects of 4,4'-dichloro-diphenyl diselenide (ClPhSe)(2) on the toxicity induced by mercuric chloride (HgCl(2)) were investigated and compared with diphenyl diselenide (PhSe)(2). Mice received HgCl(2) for three days and, on the third day, received (PhSe)(2) or (ClPhSe)(2). The results verified that the administration of (ClPhSe)(2) in mice exposed to HgCl(2) increased renal δ-aminolevulinate dehydratase (δ-ALA-D), Na(+), K(+)-ATPase activities and non-protein thiol (NPSH) levels and also decreased thiobarbituric acid-reactive substances (TBARS) and ascorbic acid levels, when compared to mice exposed to HgCl(2)+(PhSe)(2). Plasma and urinary protein, hemoglobin and hematocrit levels and histological parameters were also ameliorated in mice exposed to HgCl(2)+(ClPhSe)(2). In addition, the hepatic damage in mice exposed to HgCl(2)+(PhSe)(2) was reduced in animals exposed to (ClPhSe)(2). To sum up, the introduction of a functional group (chloro) in the aromatic ring of diaryl diselenide reduced the toxicity of this compound in liver and kidney of mice exposed to HgCl(2).


Subject(s)
Antioxidants/pharmacology , Benzene Derivatives/pharmacology , Hazardous Substances/toxicity , Mercuric Chloride/toxicity , Organoselenium Compounds/pharmacology , Animals , Ascorbic Acid/metabolism , Dose-Response Relationship, Drug , Kidney/metabolism , Liver/metabolism , Male , Mice , Porphobilinogen Synthase/metabolism , Thiobarbituric Acid Reactive Substances/metabolism
11.
Neurochem Res ; 37(10): 2249-58, 2012 Oct.
Article in English | MEDLINE | ID: mdl-22846969

ABSTRACT

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) (50 mg/kg), administered 30 min 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-1ß, 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.


Subject(s)
Benzene Derivatives/pharmacology , Brain Ischemia/prevention & control , Cytokines/physiology , Inflammation Mediators/physiology , Organoselenium Compounds/pharmacology , Oxidative Stress , Animals , Male , Rats , Rats, Wistar
12.
Behav Brain Res ; 230(1): 100-7, 2012 Apr 21.
Article in English | MEDLINE | ID: mdl-22342489

ABSTRACT

The objective of present study was to investigate the protective effect of M-NC against aß (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) aß, (III) M-NC, (IV) M-F, (V) M-NC+aß and (VI) M-F+aß. 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, aß 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 aß peptide caused learning and memory deficits in mice. Histological analysis demonstrated neuronal loss, intense cellular accumulation and chromatolysis caused by aß peptide. Furthermore, this study showed that oxidative stress was increased in mice that received aß peptide. An important finding of the present study was the protective effect of M-NC in damage induced by aß 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 aß peptide.


Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Learning Disabilities/prevention & control , Memory Disorders/prevention & control , Nanocapsules/therapeutic use , Thiazines/therapeutic use , Thiazoles/therapeutic use , Amyloid beta-Peptides/toxicity , Analysis of Variance , Animals , Avoidance Learning/drug effects , Behavior, Animal , Body Weight/drug effects , Brain/drug effects , Brain/metabolism , Catalase/metabolism , Disease Models, Animal , Exploratory Behavior/drug effects , Glutathione/metabolism , Glutathione Peroxidase/metabolism , Glutathione Reductase/metabolism , Glutathione Transferase/metabolism , Learning Disabilities/chemically induced , Learning Disabilities/pathology , Male , Maze Learning/drug effects , Meloxicam , Memory Disorders/chemically induced , Memory Disorders/pathology , Mice , Peptide Fragments/toxicity , Superoxide Dismutase/metabolism , Time Factors
13.
Exp Toxicol Pathol ; 63(4): 331-5, 2011 May.
Article in English | MEDLINE | ID: mdl-20307962

ABSTRACT

In the present study, the protective effect of binapthyl diselenide [(NapSe)(2)] was investigated on glycerol-induced renal damage in rats. Adult male Wistar rats were treated with (NapSe)(2) (50 mg/kg, orally) or vehicle. After 24 h (NapSe)(2) treatment, the animals received an intramuscular injection of glycerol (8 ml/kg, dissolved in saline) or vehicle as a divided dose into the hind limbs. Twenty-four hours afterwards, rats were euthanized and the levels of urea and creatinine were measured in plasma. Non-protein thiol (NPSH) levels and catalase (CAT) activity were evaluated in renal homogenates. Histopathological evaluations were also performed in kidneys of rats. The rats exposed to glycerol presented swelling of the proximal and distal tubules with evidence of cell damage and death. Glycerol-exposed rats presented an increase in renal failure markers (plasmatic urea and creatinine levels) and a reduction in renal CAT activity. No change was observed in NPSH levels in kidneys of rats exposed to glycerol. (NapSe)(2) protected against the alterations caused by glycerol in rats. (NapSe)(2) increased per se NPSH levels (33%) in kidneys of rats. In conclusion, the results demonstrated that treatment with (NapSe)(2) protected against renal damage induced by glycerol in rats, probably due to its antioxidant effect.


Subject(s)
Acute Kidney Injury/enzymology , Acute Kidney Injury/prevention & control , Antioxidants/pharmacology , Catalase/metabolism , Organoselenium Compounds/pharmacology , Acute Kidney Injury/pathology , Animals , Glycerol/toxicity , Male , Rats , Rats, Wistar , Solvents/toxicity
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