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1.
Metab Brain Dis ; 38(8): 2603-2613, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37906392

RESUMO

Hypothyroidism causes learning and memory impairment. Considering the neuroprotective properties of thiamine (Vitamin B1), this study was conducted to investigate the effects of thiamine on acetylcholinesterase (AChE) activity, oxidative damage, and memory deficits in hypothyroid rats.In this study, 50 rats (21 days old) were randomly divided into 5 groups and treated with propylthiouracil (0.05% in drinking water) and thiamine (50, 100, and 200 mg/kg, oral) for 7 weeks. Following that, Morris water maze (MWM) and passive avoidance (PA) tests were performed. Finally, oxidative stress indicators and AChE activity were measured in brain tissue.Treatment of hypothyroid rats with thiamine, especially at 100 and 200 mg/kg, alleviated the ability to remember the location of the platform as reflected by less time spent and distance to reach the platform, during the MWM test (P < 0.05 to P < 0.001). In the PA test, the latency to enter the dark chamber and light stay time were increased in rats who received thiamine compared to the hypothyroid group (P < 0.05 to P < 0.001). In addition, thiamine increased the levels of total thiol groups and superoxide dismutase while decreasing the levels of malondialdehyde and AChE.Our results suggest that thiamine supplementation could effectively improve memory loss in a rat model of hypothyroidism. The positive effects of thiamin on the learning and memory of hypothyroid rats may be due to amelioration of redox hemostasis and cholinergic disturbance.


Assuntos
Acetilcolinesterase , Hipotireoidismo , Ratos , Animais , Acetilcolinesterase/metabolismo , Ratos Wistar , Hipocampo/metabolismo , Estresse Oxidativo , Transtornos da Memória/tratamento farmacológico , Hipotireoidismo/induzido quimicamente , Hipotireoidismo/complicações , Hipotireoidismo/tratamento farmacológico , Tiamina/farmacologia , Tiamina/uso terapêutico , Aprendizagem em Labirinto
2.
Toxicol Mech Methods ; 33(3): 206-214, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35941716

RESUMO

Some commonly used chemicals have teratogenic effects. Perchloroethylene (PCE) is a liquid that is widely used in various industries and drying clothes. In this study, the teratogenic effects of PCE in rat embryos were investigated. In this experimental study, 32 adult Wistar female rats in the weight range of 230-250 g were used. Female rats were randomly divided into 4 groups (n = 8). Control group (without PCE inhalation), experimental group G(I) (exposed to PCE 18 days prior to mating), experimental group G(II) (exposed to PCE 18 days after mating) and experimental group G(III) (exposed to PCE 18 days before and 18 days after mating). Pregnant rats were anesthetized on the 18th day of gestation and then serum and embryos were removed for the required studies. Embryos were examined for number, weight, sex, morphometric parameters of organs, and tissue samples were prepared for histological studies. Serum isolated from dams were evaluated for sexual and gonadal hormones. The results of this study showed that PCE has teratogenic effects on rat embryos. Infertility and reduced birth rate were other effects of PCE in rats. PCE has teratogenic effects and impairs the reproductive system of rats.


Assuntos
Tetracloroetileno , Gravidez , Humanos , Ratos , Feminino , Animais , Tetracloroetileno/farmacologia , Exposição por Inalação/efeitos adversos , Ratos Wistar , Reprodução , Exposição Materna/efeitos adversos
3.
Can J Physiol Pharmacol ; 100(6): 534-541, 2022 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-35395161

RESUMO

The effect of oxaprozin (OXP) on an experimental model of seizures in rats was investigated in this study. Seizures in Wistar rats (200-250 g) were induced by pentylenetetrazole (PTZ, 60 mg/kg). The anticonvulsant effect of OXP (100, 200, and 400 mg/kg, intraperitoneally) was evaluated in a seizure model. After behavioral tests, the animals underwent deep anesthesia and were put down painlessly. Animal serum was isolated for antioxidant assays (nitric oxide (NO) and glutathione (GSH)). The animals' brains were also isolated to gauge the relative expression of genes in the oxidative stress pathway (sirtuin 1 (Sirt1) and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (Pgc1α)). Intraperitoneal injection of OXP increased the mean latency of myoclonic jerks and generalized tonic-clonic seizure (GTCS) and decreased the number of myoclonic jerks and GTCS duration compared with the PTZ group. Biochemical tests showed that pretreatment with OXP was able to restore GSH serum levels and reverse the augmented NO serum levels caused by PTZ induction to the normal level. The quantitative polymerase chain reaction results also revealed that OXP counteracts the negative effects of PTZ by affecting the expression of the Sirt1 and Pgc1α genes. Overall, this study suggests the potential neuroprotective effects of the nonsteroidal, anti-inflammatory OXP drug in a model of neural impairment caused by seizures via the mechanism of inhibition of the oxidative stress pathway.


Assuntos
Anticonvulsivantes , Mioclonia , Oxaprozina , Convulsões , Animais , Anticonvulsivantes/uso terapêutico , Modelos Animais de Doenças , Glutationa/metabolismo , Mioclonia/tratamento farmacológico , Oxaprozina/uso terapêutico , Estresse Oxidativo , Pentilenotetrazol/efeitos adversos , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , Ratos , Ratos Wistar , Convulsões/induzido quimicamente , Convulsões/tratamento farmacológico , Convulsões/metabolismo , Sirtuína 1/metabolismo
4.
Drug Chem Toxicol ; 45(5): 2262-2268, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34006164

RESUMO

Sold under the brand name of Garamycin, gentamicin (GM) is an antibiotic in the category of aminoglycoside, that although does have many antibacterial properties, owing to several side effects, its consumption is confined. The current study is aimed at gauging the protective influences of human umbilical cord blood serum (hUCBS) on nephrotoxicity which is induced by GM. In this regard, in the present experimental design, twenty-eight male Wistar rats with the weights of 220 ± 20 g were categorized randomly into 4 groups of seven. The groups included GM (100 mg/kg), control as well as hUCBS at doses of one and two percent together with GM (100 mg/kg) for ten days in an intraperitoneal manner. Blood sampling was collected from the heart directly 24 h after the final injection for obtaining blood serum; the parameters of C-reactive protein (CRP), total oxidant status (TOS), interleukin (IL)-6, lactate dehydrogenase (LDH), total antioxidant capacity (TAC), creatinine (Cr), blood urea nitrogen (BUN), blood serum glutathione (GSH) were gauged in blood serum samples to evaluate renal function. Moreover, for histology, an examination of kidney tissue was performed. In comparison to those of the GM group, in the treatment group, hUCBS significantly decreased the levels of BUN, Cr, LDH, TOS, IL-6, and the CRP levels, and significantly increased the TAC and GSH levels. It was revealed that the treatment of the animals with hUCBS culminates in the reduction of GM' toxic impacts on the kidney.


Assuntos
Gentamicinas , Soro , Animais , Antibacterianos/toxicidade , Antioxidantes/farmacologia , Nitrogênio da Ureia Sanguínea , Creatinina , Sangue Fetal/metabolismo , Gentamicinas/metabolismo , Gentamicinas/toxicidade , Glutationa/metabolismo , Humanos , Rim , Masculino , Oxidantes/metabolismo , Ratos , Ratos Wistar , Soro/metabolismo
5.
Can J Physiol Pharmacol ; 95(5): 522-529, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28281782

RESUMO

Silymarin, a mixture of antihepatotoxic flavonolignans used in the treatment of liver diseases, and lactulose, a nonabsorbable synthetic disaccharide, were investigated to analyze their probable synergic and healing effects in a hepatic cirrhotic rat model. Liver damage was induced by the administration and subsequent withdrawal of thioacetamide. The significant decrease in liver enzymes and malondialdehyde levels confirmed the curative effects of silymarin and lactulose. In the silymarin + lactulose group, liver enzyme and malondialdehyde levels were significantly reduced compared with those in the thioacetamide group. All treatments led to liver regeneration and triggered enhanced regeneration. Silymarin and lactulose alone or in combination have potent curative effects and reduce thioacetamide-induced liver damage.


Assuntos
Lactulose/farmacologia , Cirrose Hepática/tratamento farmacológico , Cirrose Hepática/enzimologia , Fígado/efeitos dos fármacos , Fígado/enzimologia , Silimarina/farmacologia , Animais , Interações Medicamentosas , Lactulose/uso terapêutico , Peroxidação de Lipídeos/efeitos dos fármacos , Fígado/metabolismo , Cirrose Hepática/induzido quimicamente , Cirrose Hepática/metabolismo , Masculino , Ratos , Ratos Wistar , Silimarina/uso terapêutico , Tioacetamida/farmacologia
6.
Pharm Biol ; 53(5): 752-7, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25609148

RESUMO

CONTEXT: Zingiber officinale Roscoe (Zingiberaceae), or ginger, used in traditional Chinese medicine, has antioxidant activity and neuroprotective effects. The effects of this plant on clonic seizure have not yet been studied. OBJECTIVE: The present study evaluated the anticonvulsant effect of ginger in a model of clonic seizures induced with pentylenetetrazole (PTZ) in male mice. MATERIALS AND METHODS: The anticonvulsant effect of Z. officinale was investigated using i.v. PTZ-induced seizure models in mice. Different doses of the hydroethanolic extract of Z. officinale (25, 50, and 100 mg/kg) were administered intraperitonal (i.p.), daily for 1 week before induction of PTZ. Phenobarbital sodium (30 mg/kg), a reference standard, was also tested for comparison. The effect of ginger on to the appearance of three separate seizure endpoints, e.g., myoclonic, generalized clonic, and tonic extension phase, was recorded. RESULTS: Hydroethanolic extract of Z. officinale significantly increased the onset time of myoclonic seizure at doses of 25-100 mg/kg (55.33 ± 1.91 versus 24.47 ± 1.33 mg/kg, p < 0.001) and significantly prevented generalized clonic (74.64 ± 3.52 versus 47.72 ± 2.31 mg/kg, p < 0.001) and increased the threshold for the forelimb tonic extension (102.6 ± 5.39 versus 71.82 ± 7.82 mg/kg, p < 0.01) seizure induced by PTZ compared with the control group. DISCUSSION AND CONCLUSION: Based on the results, the hydroethanolic extract of ginger has anticonvulsant effects, possibly through an interaction with inhibitory and excitatory systems, antioxidant mechanisms, and oxidative stress inhibition.


Assuntos
Anticonvulsivantes/administração & dosagem , Pentilenotetrazol/toxicidade , Extratos Vegetais/administração & dosagem , Convulsões/prevenção & controle , Zingiber officinale , Animais , Anticonvulsivantes/isolamento & purificação , Relação Dose-Resposta a Droga , Masculino , Camundongos , Extratos Vegetais/isolamento & purificação , Convulsões/induzido quimicamente
7.
Front Pharmacol ; 15: 1379264, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38756381

RESUMO

Introduction: Alzheimer's disease (AD) causes progressive loss of cognitive function and synaptic plasticity, which is the most common form of dementia. The present study was designed to scrutinize the effects of cacao on passive avoidance memory function and to identify the roles of hippocampal synaptic plasticity and oxidative stress in an AD rat model induced by unilateral intracerebroventricular (UICV) injection of amyloid-beta (Aß). Methods: Oral administration of cacao (500 mg/kg/ day) was given for 2 consecutive months. A memory retention test was conducted 24 h after passive avoidance training was completed. Subsequently, the amplitude of population spike (PS) and slope of field excitatory postsynaptic potentials (fEPSPs) were assessed at hippocampal long-term potentiation (LTP) in perforant pathway-dentate gyrus (PP-DG) synapses. Moreover, total thiol group (TTG) and malondialdehyde (MDA) concentrations were evaluated in the plasma. Furthermore, compact Aß plaques were detected in the hippocampal DG by performing Congo red staining. Results: As a result of AD induction, passive avoidance memory was impaired; also, reduced fEPSP slopes, PS amplitudes, and content of TTG, and increase in MDA levels in the rats were observed. In contrast, cacao treatment ameliorated passive avoidance memory impairment, improved hippocampal LTP impairment, modulated oxidative-antioxidative status, and delayed Aß plaques production in AD rats. Disscussion: Conclusively, cacao alleviates Aß-induced cognitive deficit, probably by the amelioration of hippocampal LTP impairment, modulation of oxidative-antioxidative status, and inhibition of Aß plaque accumulation.

8.
Mol Neurobiol ; 2024 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-39136906

RESUMO

Alzheimer's disease (AD) is a progressive neurological disorder characterized by cognitive decline. This study was undertaken to evaluate the effects of selegiline (SEL) against AD-induced cognitive deficits and explore the possible involved mechanisms. AD was induced by unilateral intracerebroventricular (U-ICV) injection of 5 µg of amyloid beta1-42 (Aß1-42), and oral administration of SEL (0.5 mg/kg/day) was performed for 30 consecutive days. Aß injection resulted in spatial cognitive decline, as demonstrated by a decrease in the time spent in the target zone on the probe day (P < 0.01) in the Barnes maze test (BMT). This spatial cognitive decline was associated with disrupted synaptic plasticity, as indicated by reductions in both components of hippocampal long-term potentiation (LTP), namely population spike amplitude (P < 0.001) and field excitatory postsynaptic potential (P < 0.001). On the other hand, the injection of Aß resulted in oxidative stress by decreasing total thiol group (TTG) content and increasing malondialdehyde (MDA) levels in the rat plasma (P < 0.001). Additionally, the number of healthy cells in the hippocampal dentate gyrus (DG) and CA1 regions was reduced in AD rats (P < 0.001). However, oral administration of SEL improved spatial cognitive decline in the Aß-induced AD rats. The results suggest that improvement of neuroplasticity deficiency, regulation of oxidant/antioxidant status, and suppression of neuronal loss by SEL may be the mechanisms underlying its beneficial effect against AD-related spatial cognitive impairment.

9.
Brain Behav ; 14(6): e3599, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38873869

RESUMO

BACKGROUND: Alzheimer's disease (AD) is a complex and common neurodegenerative disorder. The present study aimed to investigate the potential effects of selegiline (SEL) on various aspects of memory performance, anxiety, and oxidative stress in an AD rat model induced by intracerebroventricular injection of amyloid beta1-42 (Aß1-42). METHODS: Oral administration of SEL at a dose of 0.5 mg/kg/day was performed for 30 consecutive days. Following the 30 days, several tests, including the open-field, elevated plus-maze, novel object recognition, Morris water maze, and passive avoidance learning were conducted to assess locomotor activity, anxiety-like behavior, recognition memory, spatial memory, and passive avoidance memory, respectively. RESULTS: The results indicate that the induction of AD in rats led to recognition memory, spatial memory, and passive avoidance memory impairments, as well as increased anxiety. Additionally, the AD rats exhibited a decrease in total antioxidant capacity and an increase in total oxidant status levels, suggesting an imbalance in oxidative-antioxidant status. However, the administration of SEL improved memory performance, reduced anxiety, and modulated oxidative-antioxidant status in AD rats. CONCLUSIONS: These findings provide evidence that SEL may alleviate anxiety-like behavior and cognitive deficits induced by Aß through modulation of oxidative-antioxidant status.


Assuntos
Peptídeos beta-Amiloides , Ansiedade , Comportamento Animal , Transtornos da Memória , Selegilina , Animais , Masculino , Ratos , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/induzido quimicamente , Peptídeos beta-Amiloides/metabolismo , Antioxidantes/farmacologia , Antioxidantes/administração & dosagem , Ansiedade/tratamento farmacológico , Ansiedade/induzido quimicamente , Aprendizagem da Esquiva/efeitos dos fármacos , Comportamento Animal/efeitos dos fármacos , Modelos Animais de Doenças , Aprendizagem em Labirinto/efeitos dos fármacos , Transtornos da Memória/tratamento farmacológico , Transtornos da Memória/induzido quimicamente , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/administração & dosagem , Estresse Oxidativo/efeitos dos fármacos , Fragmentos de Peptídeos , Ratos Wistar , Reconhecimento Psicológico/efeitos dos fármacos , Selegilina/farmacologia , Selegilina/administração & dosagem , Memória Espacial/efeitos dos fármacos
10.
Neurosci Insights ; 19: 26331055241280638, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39314637

RESUMO

Background: Alzheimer's disease (AD) is a progressive neurological disorder characterized by a wide range of cognitive and non-cognitive impairments. The present study was designed to investigate the potential effects of cacao on cognitive and non-cognitive performance and to identify the role of oxidative stress in an AD animal model induced by unilateral intracerebroventricular (U-ICV) injection of amyloid beta1-42 (Aß1-42). Methods: Oral administration of cacao (0.5 g/kg/day) was performed for 60 consecutive days. Following 60 days, the open-field (OF) test, elevated plus-maze (EPM) test, novel object recognition (NOR) test, Barnes maze (BM) test, and Morris water maze (MWM) test were used to evaluate locomotor activity, anxiety-like behavior, recognition memory, and spatial memory, respectively. Total oxidant status (TOS) and total antioxidant capacity (TAC) in plasma were also examined. Furthermore, the number of healthy cells in the hippocampus's dentate gyrus (DG), CA1, and CA3 regions were identified using hematoxylin and eosin staining. Results: The results indicated that the injection of Aß1-42 in rats led to recognition memory and spatial memory impairments, as well as increased anxiety. This was accompanied by decreased total antioxidant capacity (TAC), increased total oxidative stress (TOS), and increased neuronal death. Conversely, cacao treatment in AD rats improved memory function, reduced anxiety, modulated oxidative stress balance, and decreased neuronal death. Conclusion: The findings suggest that cacao's ability to improve the balance between oxidants and antioxidants and prevent neuronal loss may be the mechanism underlying its beneficial effect against AD-related cognitive and non-cognitive impairments.

11.
Neurosci Insights ; 18: 26331055231198013, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37720697

RESUMO

Epilepsy is one of the most common neurological diseases, which is caused by abnormal brain activity. A wide variety of studies have shown the importance of the phosphatidylinositol-3-kinase (PI3K) signaling pathway in epilepsy pathogenesis. Duvelisib (DUV) is a selective inhibitor of PI3K. The present study investigated the anticonvulsant potential of DUV in a rat model of pentylenetetrazole (PTZ)-induced convulsions. Male Wistar rats (200-250 g, 8 weeks old) were injected intraperitoneally (IP) with DUV at different doses of 5 and 10 mg/kg, or vehicle 30 minutes prior to PTZ (70 mg/kg, IP) treatment. Based on Racine's scale, behavioral seizures were assessed. The results showed that pretreatment with DUV prolonged the seizure stages according to the Racine scale, significantly decreased the duration of general tonic-clonic seizure and reduced the number of myoclonic jerks (P < .05). In conclusion, we found that PI3K antagonist DUV significantly reduced PTZ-induced seizures, indicating that DUV exerts an anticonvulsant effect by inhibiting PI3K signaling pathway.

12.
Endocrinol Diabetes Metab ; 6(5): e438, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37403247

RESUMO

INTRODUCTION: Spermatogenesis is significantly influenced by the thyroid gland. Thyroid disorders can be caused by a variety of factors. Traditionally, Ellettaria cardamomum has been used to treat a variety of ailments. The effects of E. cardamomum extract (ECE) on spermatogenesis in hypothyroid mice were investigated in this study. METHODS: In this study 42 male mice, weighing (25-35 g) were randomly divided in six groups: control group (taking normal saline, 0.5 mL/day, by oral gavage [P.O.]), hypothyroid group (taking 0.1% propylthiouracil in drinking water for 2 weeks), hypothyroid groups treated by levothyroxine (15 mg/kg/day, P.O.) and hypothyroid groups treated by ECE (100, 200 and 400 mg/kg/day, P.O.). After the end of experiments the mice were anaesthetised and blood samples were collected for hormonal analysis. RESULTS: The sperm count and microscopic studies of testes were done also. Our results showed that the T3 , T4 , testosterone levels and spermatogenesis in hypothyroid animals decreased and thyroid-stimulating hormone, follicle-stimulating hormone and luteinizing hormone increased compared with control group. Treatment by ECE reverse these effects in comparison with hypothyroid group. CONCLUSIONS: According to our findings, the ECE may stimulates thyroid gland function and increases testosterone and spermatogenesis.


Assuntos
Elettaria , Hipotireoidismo , Masculino , Animais , Camundongos , Propiltiouracila/efeitos adversos , Camundongos Endogâmicos BALB C , Sementes , Hipotireoidismo/induzido quimicamente , Hipotireoidismo/tratamento farmacológico , Espermatogênese , Testosterona
13.
Mol Neurobiol ; 60(5): 2507-2519, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36680733

RESUMO

Alzheimer's disease (AD), the most common form of dementia, is characterized by a progressive decline in cognitive performance and memory formation. The present study was designed to investigate the effect of policosanol (PCO) on cognitive function, oxidative-antioxidative status, and amyloid-beta (Aß) plaque formation in an AD rat model induced by intracerebroventricular (ICV) injection of Aß1-40. Healthy adult male Wistar rats were randomly divided into seven groups: control, sham (5 µL, ICV injection of phosphate-buffered saline), AD model (5 µL, ICV injection of Aß), acacia gum (50 mg/kg, 8 weeks, gavage), PCO (50 mg/kg, 8 weeks, gavage), AD + acacia gum (50 mg/kg, 8 weeks, gavage), and AD + PCO (50 mg/kg, 8 weeks, gavage). During the ninth and tenth weeks of the study, the cognitive function of the rats was assessed by commonly used behavioral paradigms. Subsequently, oxidative-antioxidative status was examined in the serum. Moreover, compact Aß plaques were detected by Congo red staining. The results showed that injection of Aß impaired recognition memory in the novel object recognition test, reduced the spatial cognitive ability in the Morris water maze, and alleviated retention and recall capability in the passive avoidance task. Additionally, injection of Aß resulted in increased total oxidant status, decreased total antioxidant capacity, and enhanced Aß plaque formation in the rats. Intriguingly, PCO treatment improved all the above-mentioned neuropathological changes in the Aß-induced AD rats. The results suggest that PCO improves Aß-induced cognitive decline, possibly through modulation of oxidative-antioxidative status and inhibition of Aß plaque formation.


Assuntos
Doença de Alzheimer , Ratos , Masculino , Animais , Doença de Alzheimer/complicações , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/induzido quimicamente , Ratos Wistar , Goma Arábica/efeitos adversos , Transtornos da Memória/complicações , Transtornos da Memória/tratamento farmacológico , Transtornos da Memória/patologia , Peptídeos beta-Amiloides/toxicidade , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Modelos Animais de Doenças , Aprendizagem em Labirinto , Hipocampo/patologia , Fragmentos de Peptídeos/toxicidade
14.
Psychopharmacology (Berl) ; 240(4): 755-767, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36723631

RESUMO

RATIONALE: Alzheimer's disease (AD) is a chronic neurodegenerative disorder characterized by cognitive decline and synaptic failure. OBJECTIVE: The present study was designed to explore the possible protective effects of policosanol (PCO) on spatial cognitive capacity, long-term potentiation (LTP) induction, oxidant/antioxidant status, and Aß plaques formation in an AD rat model induced by intracerebroventricular (ICV) injection of Aß1-40. METHODS: Healthy adult male Wistar rats were randomly divided into control, sham (ICV injection of 5 µl phosphate-buffered saline), AG (50 mg/kg; P.O., as PCO vehicle), PCO (50 mg/kg; P.O.), AD model (ICV injection of 5 µl Aß), AD + AG (50 mg/kg; P.O.), and AD + PCO (50 mg/kg; P.O.). Treatments were performed for eight consecutive weeks. At the end of the treatment course, spatial learning and memory functions, hippocampal long-term potentiation (LTP) induction, malondialdehyde (MDA), and total thiol group (TTG) levels, as well as the formation of Aß plaques, were examined. RESULTS: The results showed that injection of Aß reduced spatial learning and memory abilities in the Barnes maze test, which was accompanied by decreases in field excitatory postsynaptic potential (fEPSP) slope, population spike (PS) amplitude, and TTG level and increases in Aß plaque accumulation and MDA content. In contrast, PCO treatment improved all the above-mentioned changes in the Aß-infused rats. CONCLUSIONS: The results suggest that amelioration of hippocampal synaptic plasticity impairment, modulation of oxidant/antioxidant status, and inhibition of Aß plaque formation by PCO may be the mechanisms behind its protective effect against AD-associated spatial cognitive decline.


Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Ratos , Masculino , Animais , Doença de Alzheimer/induzido quimicamente , Ratos Wistar , Antioxidantes/farmacologia , Transtornos da Memória/complicações , Peptídeos beta-Amiloides , Hipocampo , Potenciação de Longa Duração , Fragmentos de Peptídeos , Oxidantes/efeitos adversos , Modelos Animais de Doenças
15.
J Surg Res ; 178(1): 524-8, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22521221

RESUMO

BACKGROUND: The protective effect of hypothyroidism against ischemic or toxic conditions has been shown in various tissues. We investigated the effect of propylthiouracil (PTU)/methimazole (MMI)-induced hypothyroidism and acute local effect of MMI on the outcome of lethal ischemia in random-pattern skin flaps. MATERIALS AND METHODS: Dorsal flaps with caudal pedicles were elevated at midline and flap survival was measured at the seventh day after surgery. The first group, as control, received 1 mL of 0.9% saline solution in the flap before flap elevation. In groups 2 and 3, hypothyroidism was induced by administration of either PTU 0.05% or MMI 0.04% in drinking water. The next four groups received local injections of MMI (10, 20, 50, or 100 µg/flap) before flap elevation. Local PTU injection was ignored due to insolubility of the agent. RESULTS: Hypothyroidism was induced in chronic PTU- and MMI-treated groups, and animals in these groups showed significant increase in their flap survival, compared to control euthyroid rats (79.47% ± 10.49% and 75.48% ± 12.93% versus 52.26% ± 5.75%, respectively, P < 0.01). Acute local treatment of skin flaps with MMI failed to significantly affect the flap survival. CONCLUSION: This study demonstrates for the first time that hypothyroidism improves survival of random-pattern skin flaps in rats.


Assuntos
Procedimentos Cirúrgicos Dermatológicos/métodos , Hipotireoidismo/induzido quimicamente , Isquemia/tratamento farmacológico , Metimazol/farmacologia , Propiltiouracila/farmacologia , Retalhos Cirúrgicos/irrigação sanguínea , Animais , Antitireóideos/farmacologia , Modelos Animais de Doenças , Isquemia/prevenção & controle , Masculino , Ratos , Ratos Sprague-Dawley , Procedimentos de Cirurgia Plástica/métodos , Pele/irrigação sanguínea , Glândula Tireoide/efeitos dos fármacos
16.
J Mol Neurosci ; 72(4): 880-887, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35084669

RESUMO

There is substantial evidence that anti-inflammatory agents and antioxidants have neuroprotective properties and may be useful in the treatment of neurodegenerative disorders. In this regard, the effects of oxaprozin (OXP) (a nonsteroidal anti-inflammatory drug) on the experimental model of seizure and memory impairment caused by seizures in rats were investigated in the present study. Seizures in male Wistar rats (200-250 g, 8 weeks) were induced by pentylenetetrazol (PTZ, 60 mg/kg). The anticonvulsant effects of OXP (100, 200, and 400 mg/kg, administered intraperitoneally) were evaluated in the seizure model. The effect on memory was assessed using the passive avoidance (PA) test. After behavioral tests, the animals underwent deep anesthesia and were euthanized painlessly. Animal serum was isolated for antioxidant assays (MDA and GPx). The animals' brains (hippocampus) were also isolated to gauge the relative expression of genes in the oxidative stress pathway (Nrf2/HO-1). Intraperitoneal injection of OXP decreased the mean score on the Racine scale compared to the PTZ group. Moreover, in the PA test, OXP caused a significant increase in retention latency (RL) and total time spent in the light compartment (TLC) compared to the PTZ group. Biochemical tests showed that OXP was able to significantly increase GPx serum levels and significantly reduce MDA serum levels compared to the PTZ group. Quantitative polymerase chain reaction (qPCR) results also revealed that OXP counteracted the negative effects of PTZ by significantly increasing the expression of the Nrf2 and Hmox1 genes. Overall, this study suggests the potential neuroprotective effects of the nonsteroidal anti-inflammatory drug OXP in a model of memory impairment caused by seizures via inhibition of the oxidative stress pathway.


Assuntos
Fator 2 Relacionado a NF-E2 , Pentilenotetrazol , Animais , Masculino , Ratos , Anticonvulsivantes/farmacologia , Anticonvulsivantes/uso terapêutico , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Modelos Animais de Doenças , Transtornos da Memória/tratamento farmacológico , Transtornos da Memória/etiologia , Modelos Teóricos , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Oxaprozina , Estresse Oxidativo , Pentilenotetrazol/toxicidade , Ratos Wistar , Convulsões/tratamento farmacológico , Convulsões/etiologia , Transdução de Sinais
17.
J Tradit Chin Med ; 42(5): 741-748, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-36083481

RESUMO

OBJECTIVE: To assess the protective effect of dark chocolate (DC) on the letrozole-induced rat model of polycystic ovary syndrome (PCOS). METHODS: In this experimental study, 32 female Wistar rats, weighing (200 ± 20) g, were randomly categorized into 4 groups including control, letrozole (1 mg·kg·d), metformin (500 mg·kg·d) along with letrozole, and DC (500 mg·kg·d) along with letrozole for 28 d by oral gavage. Twenty-four hours after the last supplementation, direct blood sampling was taken from the heart to obtain blood serum for evaluation of sex hormones and gonadotropins, oxidative parameters, inflammatory cytokines, and ovarian tissue was examined for histology. RESULTS: The DC treatment significantly improved PCOS signs, as demonstrated by the significant restoration of ovarian morphology and physiological functions as compared with the letrozole group. DC treatment also decreased ovarian interleukin-1ß and tumor necrosis factor-α levels and improved total oxidative/antioxidative status as compared with the letrozole group. CONCLUSIONS: Treating the animals with DC could alleviate the PCOS symptoms and reduced the toxic effects of letrozole in the ovary. This effect may mediate through antioxidant and antiinflammatory properties.


Assuntos
Chocolate , Letrozol , Síndrome do Ovário Policístico , Animais , Antioxidantes , Modelos Animais de Doenças , Feminino , Letrozol/toxicidade , Síndrome do Ovário Policístico/induzido quimicamente , Síndrome do Ovário Policístico/tratamento farmacológico , Síndrome do Ovário Policístico/patologia , Ratos , Ratos Wistar
18.
Biomed Pharmacother ; 135: 111230, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33434853

RESUMO

Diabetes mellitus is mainly associated with degeneration of the central nervous system, which eventually leads to cognitive deficit. Although some studies suggest that exercise can improve the cognitive decline associated with diabetes, the potential effects of endurance training (ET) accompanied by Matricaria chamomilla (M.ch) flowers extract on cognitive impairment in type 2 diabetes has been poorly understood. Forty male Wistar rats were randomized into 5 equal groups of 8: healthy-sedentary (H-sed), diabetes-sedentary (D-sed), diabetes-endurance training (D-ET), diabetes-Matricaria chamomilla. (D-M.ch), and diabetes-endurance training-Matricaria chamomilla. (D-ET-M.ch). Nicotinamide (110 mg/kg, i.p.) and Streptozotocin (65 mg/kg, i.p.) were utilized to initiate type 2 diabetes. Then, ET (5 days/week) and M.ch (200 mg/kg body weight/daily) were administered for 12 weeks. After 12 weeks of the experiment, cognitive functions were assessed using the Morris Water Maze (MWM) test and a passive avoidance paradigm using a shuttle box device. Subsequently, using crystal violet staining, neuron necrosis was examined in the CA3 area of the hippocampus. Diabetic rats showed cognitive impairment following an increase in the number of necrotic cells in region CA3 of the hippocampal tissue. Also, diabetes increased serum levels of lipid peroxidation and decreased total antioxidant capacity in serum and hippocampal tissue. ET + M.ch treatment prevented the necrosis of neurons in the hippocampal tissue. Following positive changes in hippocampal tissue and serum antioxidant enzyme levels, an improvement was observed in the cognitive impairment of the diabetic rats receiving ET + M.ch. Therefore the results showed that treatment with ET + M.ch could ameliorate memory and inactive avoidance in diabetic rats. Hence, the use of ET + M.ch interventions is proposed as a new therapeutic perspective on the death of hippocampal neurons and cognitive deficit caused by diabetes.


Assuntos
Comportamento Animal/efeitos dos fármacos , Região CA3 Hipocampal/efeitos dos fármacos , Cognição/efeitos dos fármacos , Disfunção Cognitiva/prevenção & controle , Diabetes Mellitus Experimental/terapia , Diabetes Mellitus Tipo 2/terapia , Treino Aeróbico , Matricaria , Condicionamento Físico Animal , Extratos Vegetais/farmacologia , Animais , Região CA3 Hipocampal/metabolismo , Região CA3 Hipocampal/patologia , Disfunção Cognitiva/metabolismo , Disfunção Cognitiva/patologia , Disfunção Cognitiva/psicologia , Terapia Combinada , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/patologia , Diabetes Mellitus Experimental/psicologia , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/patologia , Diabetes Mellitus Tipo 2/psicologia , Flores , Peroxidação de Lipídeos , Masculino , Matricaria/química , Teste do Labirinto Aquático de Morris/efeitos dos fármacos , Necrose , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/isolamento & purificação , Ratos Wistar
19.
Basic Clin Pharmacol Toxicol ; 128(2): 268-274, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32989909

RESUMO

Gentamicin (GM) is an aminoglycoside antibiotic that despite its antibacterial effects, its use is restricted due to numerous side effects. The umbilical cord serum contains various biomolecules that have protective impacts on the damaged tissues. The aim of this study was to gauge the protective effect of human umbilical cord blood serum (hUCBS) on GM-induced hepatotoxicity. In this experimental study, 28 male Wistar rats, weighing 220 ± 20 g, were randomly categorized into 4 groups including control, GM (100 mg/kg), hUCBS at doses of 1 and 2% along with GM (100 mg/kg) for 10 days, intraperitoneally. Twenty-four hours after the last injection, direct blood sampling was taken from the heart to obtain blood serum and liver enzymes, inflammatory cytokines and liver tissue were examined for histology. GM causes necrosis and inflammation in liver tissue. Liver enzyme and inflammatory cytokine levels were significantly increased in the GM group. Human umbilical cord blood serum significantly decreased liver enzyme and inflammatory cytokines levels in the experimental groups compared to the GM group. GM causes liver damage such as the inflammation and necrosis in liver tissue. Treating the animals with hUCBS reduced the toxic effects of GM in the liver.


Assuntos
Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Sangue Fetal/metabolismo , Fígado/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Animais , Anti-Inflamatórios/metabolismo , Antioxidantes/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/patologia , Citocinas/metabolismo , Modelos Animais de Doenças , Feminino , Gentamicinas , Humanos , Mediadores da Inflamação/metabolismo , Fígado/metabolismo , Fígado/patologia , Masculino , Necrose , Gravidez , Ratos Wistar
20.
Avicenna J Phytomed ; 11(2): 199-209, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33907678

RESUMO

OBJECTIVE: Protective effects of raspberry (Rubus fruticosus L.) fruit extract on pituitary-gonadal axis and testicular tissue in diabetic male rats, were investigated. MATERIALS AND METHODS: Sixty male rats were divided into control, sham (saline treated), streptozotocin (STZ)-diabetic, and STZ-diabetic animals treated with 50, 100 and 200 mg/kg/day of raspberry extract. After 4 weeks, blood samples were obtained and left testes were removed and prepared for histopathological studies. Serum levels of Luteinizing hormone (LH), Follicle stimulating hormone (FSH), testosterone, Nitric oxide (NO), and malondialdehyde (MDA), as well as superoxide dismutase (SOD) and catalase (CAT) activity level were assayed. Sperm number and motility in the epididymis samples were measured. Data were analyzed using ANOVA (one-way analysis of variance). RESULTS: Serum levels of LH, FSH and MDA significantly increased in diabetic rats, however, treatment with the extract significantly reversed the alterations. Serum levels of testosterone and NO, activity of SOD and CAT, and sperm number and motility significantly decreased and severe destruction of testicular histology was observed in diabetic animals while treatment with the extract significantly reversed the pathologic alterations observed in diabetic rats. According to the results, 100 and 200 mg/kg of the extract were able to effectively reverse the diabetes complications. CONCLUSION: Our findings demonstrated that the fruit extract of raspberry has protective effects on male reproductive system in diabetic rats partially due to its improving effects on NO system, and SOD and CAT activity.

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