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1.
Inflammopharmacology ; 2024 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-39312096

RESUMO

BACKGROUND AND AIM: Zhumeria majdae, a unique native plant of southern Iran, has been traditionally used to treat various health issues. Preclinical studies suggest its therapeutic potential for immunological and inflammatory disorders. This study investigates the effect of Z. majdae essential oil (ZMEO) on TNBS-induced colitis in rats, focusing on the NF-κB/p38 MAPK/Nrf-2 pathway. EXPERIMENTAL PROCEDURE: Forty-eight male Wistar rats were used, with all groups except the sham group receiving a single intra-rectal dose of TNBS. Three different doses of ZMEO and also 1 mg/kg dexamethasone were administered orally for 2 weeks. Colon tissue was analyzed for ulcer index, histological changes, inflammatory cytokines, apoptotic factors, and levels of NF-κB, p38 MAPK, and Nrf-2. KEY RESULTS: GC-mass analysis identified 25 compounds with linalool (52.01%) and camphor (31.01%) as the major compounds in ZMEO. ZMEO ameliorated colon injuries, reduced ulcer index, and prevented the elevation of pro-inflammatory cytokines and pro-apoptotic proteins. It also increased the levels of IL-10 and Bcl-2 proteins. Furthermore, ZMEO decreased the expression of p-NF-κB and p38 MAPK while increasing the expression of pNrf-2. CONCLUSIONS: ZMEO mitigates colon damage associated with IBD by suppressing inflammatory cytokines and pro-apoptotic proteins possibly through modulating the NF-κB/p38 MAPK/Nrf-2 signaling pathway.

2.
Ann Med Surg (Lond) ; 86(5): 2657-2664, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38694306

RESUMO

Background and purpose: Nonalcoholic fatty liver disease (NAFLD) is a growing problem with a significant burden. Lifestyle modification is the recommended treatment, but researchers are exploring other options. This study focused on the effects of Fumaria parviflora (FP) extracts on NAFLD induced by a high-fat diet in rats. Experimental approach: Thirty-five 10-week-old male Wister-Albino rats were divided into seven groups: normal diet control, high fat diet control, high fat diet with oral normal saline gavage, high fat diet with oral Atorvastatin gavage, and three groups receiving high fat diet with FP extract in 200 mg/kg, 400 mg/kg, and 700 mg/kg.Blood samples of rats were used for the measurement of total cholesterol (TC), low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglyceride (TG), alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP).1×1 cm Liver biopsies were taken, stained with Trichrome Stain (Masson) and Hematoxylin and eosin (H&E) stain for evaluation by a pathologist. Findings/results: Lab results showed that FP extract inhibits weight gain, has positive effects on triglyceride and alkaline phosphatase levels, and reduces hepatocyte ballooning and inflammation in rats. Conclusion: FP extract may lower liver enzymes and have a positive impact on triglyceride, LDL, and HDL levels in rats with NAFLD.

3.
Acta Neurobiol Exp (Wars) ; 84(1): 59-69, 2024 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-38587323

RESUMO

Nicotine is a psychostimulant that induces neurochemical and behavioral changes upon chronic administration, leading to neurodegenerative conditions associated with smoking. As of now, no preventive or therapeutic strategies are known to counteract nicotine­induced neurodegeneration. In this study, we explore the neuroprotective effects of crocin, a bioactive agent commonly found in saffron - a spice derived from the flower of Crocus sativus - using a rat model. The dose­dependent effects of crocin were evaluated in nicotine­induced neurodegeneration and compared with a control group. Neurobehavioral changes, assessed through the elevated plus maze, the open field test, the forced swim test, and the Morris water maze, as well as oxidative stress in the hippocampus, were evaluated. Interestingly, nicotine administration resulted in depression, anxiety, and abnormal motor and cognitive functions, while crocin treatment protected the rat brain from these abnormalities. The beneficial effects of crocin were associated with reduced oxidative stress biomarkers such as malondialdehyde, along with increases in superoxide dismutase, glutathione peroxidase, and glutathione reductase activities. These results demonstrate that crocin can mitigate nicotine­induced neurodegeneration by reducing oxidative stress, potentially offering a protective measure against neurodegenerative effects in smokers.


Assuntos
Crocus , Ratos , Animais , Crocus/química , Crocus/metabolismo , Nicotina/farmacologia , Carotenoides/farmacologia , Carotenoides/uso terapêutico , Estresse Oxidativo , Antioxidantes/farmacologia , Antioxidantes/metabolismo
4.
Mol Biol Rep ; 51(1): 65, 2024 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-38170306

RESUMO

BACKGROUND: Methylphenidate (MPH) abuse has been criticized for its role in neurodegeneration. Also, a high risk of seizure was reported in the first month of MPH treatment. Topiramate, a broad-spectrum Antiepileptic Drug (AED), has been used as a neuroprotective agent in both aforementioned complications. Nanotechnology is introduced to increase desirable neurological treatment with minimum side effects. We aimed to investigate the potential neuroprotective activity of topiramate loaded on nanoparticles. METHODS AND RESULTS: MTT assay was performed to evaluate the cellular cytotoxicity of Mesoporous Silica Nanoparticles (MSN). Male rats were randomly divided into eight groups. Rats received an intraperitoneal (i.p) MPH (10 mg/kg) injection and a daily oral dose of topiramate (TPM, 30 mg/kg), MSN with Zn core (10 and 30 mg/kg), and MSN with Cu core (10 and 30 mg/kg) for three weeks. On day 21, a seizure was induced by a single injection of pentylenetetrazole (PTZ) to evaluate the protective effects of TPM-loaded nanoparticles on seizure latency and duration following MPH-induced neurotoxicity. Moreover, the hippocampal content of tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), malondialdehyde (MDA), and the anti-oxidant enzymes (SOD, GPx, and GR) activities were assessed. Also, BAX and Bcl-2 as two main apoptotic markers were evaluated. RESULTS: MPH neurotoxicity was observed as a raised duration and reduced latency in PTZ-induced seizure. However, TPM-loaded MSN with Zn species (NE) treatment reduced the duration and improved the latency time. Also, NE and, somewhat, TPM-loaded MSN with Cu species (NM) administration reduced inflammatory cytokines, MDA, and Bax levels and increased activities in the rat hippocampus. CONCLUSION: TPM-loaded nanoparticles could be used as neuroprotective agents against MPH-induced neurodegeneration by improving seizure parameters and reducing inflammatory, oxidant, and apoptotic factors.


Assuntos
Metilfenidato , Fármacos Neuroprotetores , Ratos , Masculino , Animais , Metilfenidato/farmacologia , Topiramato/farmacologia , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Frutose , Proteína X Associada a bcl-2 , Estresse Oxidativo , Superóxido Dismutase/metabolismo , Convulsões/induzido quimicamente , Convulsões/tratamento farmacológico
5.
Toxicol Appl Pharmacol ; 481: 116754, 2023 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-37956929

RESUMO

Glioblastoma multiforme (GBM) is one of the most vascular among solid tumors, and despite the use of multimodal therapies, the survival of these patients is poor. In order to target angiogenesis in GBM as a promising strategy, an antiangiogenic drug is required. This study was designed to evaluate the effects of sunitinib, a multityrosine kinase inhibitor with tumor proliferation and angiogenesis inhibitory properties, on GBM-bearing rats. Given the ineffective drug delivery to the brain due to the presence of the blood-brain barrier (BBB), intra-nasal (IN) drug delivery has recently been considered as a non-invasive method to bypass BBB. Therefore, in the current study, IN was used as an ideal method for the delivery of sunitinib to the brain, and the effects of this method were also compared to the OR administration of the sunitinib. GBM was induced in the brain of male Wistar rats, and they were randomly divided into 4 groups; IN-STB (sunitinib intranasal delivery), IN-sham (placebo intranasal delivery), OR-STB (sunitinib oral delivery) and OR-sham (placebo oral delivery). After the end of the treatment period, an MRI of animals' brains showed a reduction in tumor growth in the treatment groups. Immunohistochemistry revealed that sunitinib inhibits angiogenesis in GBM in both OR and IN delivery methods. Analysis of liver tissue and enzymes showed that IN delivery of sunitinib had less hepatotoxicity than the OR method. Overall, it was found that IN sunitinib delivery could be used as a potential non-hepatotoxic alternative for the treatment of GBM.


Assuntos
Neoplasias Encefálicas , Glioblastoma , Animais , Humanos , Masculino , Ratos , Angiogênese , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/patologia , Linhagem Celular Tumoral , Glioblastoma/tratamento farmacológico , Ratos Wistar , Sunitinibe/uso terapêutico
6.
Acta Neurobiol Exp (Wars) ; 83(1): 71-83, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37078816

RESUMO

The potential of minocycline to protect against methylphenidate­induced neurodegeneration has been extensively reported in the literature but the mechanism of action is still unknown. This study aims to determine the role of mitochondrial chain enzymes and redox homeostasis on the neuroprotective effects of minocycline in methylphenidate­induced neurodegeneration. Wistar adult male rats were randomly assigned to the seven experimental groups: Group 1 received saline solution; Group 2 received methylphenidate (10 mg/kg, i.p.); Groups 3, 4, 5, and 6 received methylphenidate and minocycline for 21 days; Group 7 received minocycline alone. Cognition was evaluated with the Morris water maze test. Activity of the hippocampal mitochondrial quadruple complexes I, II, III and IV, mitochondrial membrane potential, adenosine triphosphate (ATP) levels, total antioxidant capacity, and reactive oxygen species were determined. Treatment with minocycline inhibited methylphenidate­induced cognitive dysfunction. Minocycline treatment increased mitochondrial quadruple complex activities, mitochondrial membrane potential, total antioxidant capacity, and ATP levels in the dentate gyrus and cornu ammonis­1 (CA1) areas of the hippocampus. Minocycline is likely to confer neuroprotection against methylphenidate­induced neurodegeneration and cognition impairment by regulating mitochondrial activity and oxidative stress.


Assuntos
Disfunção Cognitiva , Metilfenidato , Fármacos Neuroprotetores , Ratos , Animais , Masculino , Minociclina/farmacologia , Minociclina/uso terapêutico , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Antioxidantes/metabolismo , Ratos Wistar , Disfunção Cognitiva/tratamento farmacológico , Hipocampo/metabolismo , Estresse Oxidativo , Metilfenidato/metabolismo , Metilfenidato/farmacologia , Cognição , Mitocôndrias , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico
7.
Menopause ; 30(2): 201-207, 2023 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-36696645

RESUMO

OBJECTIVES: Cornus mas fruit has various antioxidants and anti-inflammatory properties, so this study aims at assessing its effect on menopausal symptoms and sex hormones in postmenopausal women. METHODS: In the current randomized, double-blind clinical trial, 84 individuals (42 per group) were participated. C mas hydroalcoholic extract was prepared, and participants received 300 mg C mas extract or placebo three times a day (900 g in total) for 8 weeks. The demographic, dietary intake, and physical activity information were gathered. Anthropometric indices were measured by standard methods. Furthermore, menopause symptoms were assessed by Greene Climacteric Scale. Also, sex hormones were measured by enzyme-linked immunosorbent assay. RESULTS: Based on the results, there was a significant difference in total Greene score reduction between the intervention and placebo groups (-3.19 ± 0.54, -0.76 ± 0.32, and P < 0.001). In addition, vasomotor symptoms had a remarkable decrease in the C mas extract group (P < 0.001). Also, the intervention group demonstrated a decreasing trend in the number and duration of hot flushes. Moreover, follicle-stimulating hormone remarkably decreased and estradiol increased in the intervention group (P = 0.016 and P = 0.018). CONCLUSIONS: It has been found that the extract of C mas fruit has a favorable effect on vasomotor symptoms, sex hormones, and related complications in women experiencing menopausal symptoms.


Assuntos
Cornus , Pós-Menopausa , Feminino , Humanos , Frutas , Menopausa , Fogachos/tratamento farmacológico , Estradiol/uso terapêutico , Extratos Vegetais/uso terapêutico , Extratos Vegetais/farmacologia , Método Duplo-Cego
8.
J Ethnopharmacol ; 298: 115595, 2022 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-35934192

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Plantago major (P. major) has traditionally been used in Iranian Persian medicine to treat gastrointestinal ulcers and bleeding. RESEARCH OBJECTIVES: This study aimed to investigate the anti-inflammatory effects of the leaf and seed extracts of P. major in rats with acetic acid-induced ulcerative colitis (UC). MATERIALS AND METHODS: To this end, 49 rats were randomly divided into seven groups. UC was induced in all groups but the control (vehicle) group using a single intra-rectal administration of 2 ml of 4% acetic acid. Other groups received daily intraperitoneal (i.p.) injections of the seed extract of P. major (400 mg/kg and 700 mg/kg), the leaf extract of P. major (400 mg/kg and 700 mg/kg), and sulfasalazine (400 mg/kg) for seven consecutive days, respectively. The rats' rectum was surgically removed and evaluated for macroscopic and microscopic damage. The tissue levels of oxidative stress and inflammatory markers were measured using the ELISA method. RESULTS: The high-dose leaf extract significantly decreased ulcer index and histopathologic damage as well as the tissue levels of IL-6, TNF-α, PGE2, IL-1ß, MPO, and MDA compared to the damage group. The low-dose leaf extract also significantly reduced the levels of some markers. The seed extract in the two used doses caused a modest decrease in the histopathological damages and ulcer index. CONCLUSIONS: P. major leaf extract effectively reduces inflammation and mucosal damage in rats with UC, especially when administered in high doses. P. major seed extract has minimal protective effects on UC.


Assuntos
Colite Ulcerativa , Plantago , Ácido Acético/uso terapêutico , Animais , Anti-Inflamatórios/efeitos adversos , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/patologia , Colo , Irã (Geográfico) , Extratos Vegetais/efeitos adversos , Ratos , Ratos Wistar , Úlcera/tratamento farmacológico
9.
Neurotox Res ; 40(3): 689-713, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35446003

RESUMO

Neurodegeneration is a side effect of methylphenidate (MPH), and minocycline possesses neuroprotective properties. This study aimed to investigate the neuroprotective effects of minocycline against methylphenidate-induced neurodegeneration mediated by signaling pathways of CREB/BDNF and Akt/GSK3. Seven groups of seventy male rats were randomly distributed in seven groups (n = 10). Group 1 received 0.7 ml/rat of normal saline (i.p.), and group 2 was treated with MPH (10 mg/kg, i.p.). Groups 3, 4, 5, and 6 were simultaneously administered MPH (10 mg/kg) and minocycline (10, 20, 30, and 40 mg/kg, i.p.) for 21 days. Minocycline alone (40 mg/kg, i.p.) was administrated to group 7. Open field test (OFT) (on day 22), forced swim test (FST) (on day 24), and elevated plus maze (on day 26) were conducted to analyze the mood-related behaviors; hippocampal oxidative stress, inflammatory, and apoptotic parameters, as well as the levels of protein kinase B (Akt-1), glycogen synthase kinase 3 (GSK3), cAMP response element-binding protein (CREB), and brain-derived neurotrophic factor (BDNF), were also assessed. Furthermore, localization of total CREB, Akt, and GSK3 in the DG and CA1 areas of the hippocampus were measured using immunohistochemistry (IHC). Histological changes in the mentioned areas were also evaluated. Minocycline treatment inhibited MPH-induced mood disorders and decreased lipid peroxidation, oxidized form of glutathione (GSSG), interleukin 1 beta (IL-1ß), alpha tumor necrosis factor (TNF-α), Bax, and GSK3 levels. In the contrary, it increased the levels of reduced form of glutathione (GSH), Bcl-2, CREB, BDNF, and Akt-1 and superoxide dismutase (SOD), glutathione peroxidase (GPx), and glutathione reductase (GR) activities in the experimental animals' hippocampus. IHC data showed that minocycline also improved the localization and expression of CREB and Akt positive cells and decreased the GSK3 positive cells in the DG and CA1 regions of the hippocampus of MPH-treated rats. Minocycline also inhibited MPH-induced changes of hippocampal cells' density and shape in both DG and CA1 areas of the hippocampus. According to obtained data, it can be concluded that minocycline probably via activation of the P-CREB/BDNF or Akt/GSK3 signaling pathway can confer its neuroprotective effects against MPH-induced neurodegeneration.


Assuntos
Minociclina , Doenças Neurodegenerativas , Fármacos Neuroprotetores , Animais , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Glutationa/metabolismo , Quinase 3 da Glicogênio Sintase/metabolismo , Hipocampo/metabolismo , Masculino , Metilfenidato/toxicidade , Minociclina/uso terapêutico , Doenças Neurodegenerativas/induzido quimicamente , Doenças Neurodegenerativas/tratamento farmacológico , Fármacos Neuroprotetores/uso terapêutico , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Transdução de Sinais
10.
Int J Neurosci ; 132(12): 1198-1209, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33428483

RESUMO

Propose/aim of study: Forced exercise can act as a neuroprotective factor and cognitive enhancer. The aim of the current study was to evaluate the effects of forced exercise on topiramate (TPM) induced cognitive impairment and also on TPM anti-seizure activity and neurodegeneration status after seizure.Material and method: Forty adult male rats were divided into four groups receiving normal saline, TPM (100 mg/kg), TPM in combination with forced exercise and forced exercise only respectively for 21 days. MWM test, and PTZ induced seizure were used and some oxidative, inflammatory and apoptotic biomarkers were measured for assessment of experimental animals.Results: Forced exercise in combination with TPM could abolish the TPM induced cognitive impairment and potentiates its anti-seizure activity. Also forced exercise in combination with TPM decreased malondialdehyde (MDA), tumor necrosis factor alpha (TNF-α) and interleukin-1 beta (IL-1ß) and Bax protein, while caused increase in superoxide dismutase (SOD), glutathione peroxidase (GPx) and glutathione reductase (GR) activities after PTZ administration.Conclusion: It seems that forced exercise could act as an adjunct therapy with TPM for management of induced cognitive impairment and can also potentiate TPM antiepileptic and neuroprotective effects.


Assuntos
Disfunção Cognitiva , Metilfenidato , Masculino , Ratos , Animais , Topiramato/farmacologia , Anticonvulsivantes/farmacologia , Metilfenidato/farmacologia , Frutose/farmacologia , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Estresse Oxidativo , Disfunção Cognitiva/induzido quimicamente , Disfunção Cognitiva/prevenção & controle , Antioxidantes/metabolismo , Cognição
11.
Horm Mol Biol Clin Investig ; 43(1): 63-70, 2021 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-34786896

RESUMO

OBJECTIVES: Given the cardiac pathological remodeling following to anabolic androgenic steroids (AASs) consumption, we examined the effect of chronic administration of nandrolone decanoate with high-intensity endurance exercise on the left ventricular hypertrophy index, levels of hydroxyproline, tumor necrosis factor-alpha (TNF-α), adiponectin (APN) and its receptors (AdipoR1 and AdipoR2) expression in rats' hearts. METHODS: The male Wistar rats randomly divided to six groups included the control (CTL), exercise (Ex), nandrolone (Nan), vehicle (Arach), trained vehicle (Ex + Arach), and trained nandrolone (Ex + Nan) groups that were treated for eight weeks. RESULTS: Nandrolone consumption significantly enhanced the hypertrophy index (p<0.05) and exercise intensified this effect. It also increased the level of cardiac hydroxyproline (p<0.001), however exercise completely masked this effect. The values of TNF-α protein and AdipoR1 protein significantly increased in trained nandrolone-treated (Ex + Nan) group in comparison with CTL group (p<0.05), however, did not show significant alteration in Nan or Ex groups. High-intensity endurance exercise significantly enhanced the AdipoR2 protein (p<0.05), but, co-administration of nandrolone with exercise prevented this effect. The mRNA expression of AdipoR1 significantly reduced in the animals that received nandrolone for eight weeks and exercise recovered this effect (p<0.001). CONCLUSIONS: Despite an additive effect of high-intensity endurance exercise plus nandrolone on TNF-α level, their effects on hydroxyproline and APN receptors expression is incompatible in heart of rat. It is suggests a part of beneficial regulatory role of endurance exercise against nandrolone induced heart remodeling may apply through modulation of APN system.


Assuntos
Nandrolona , Condicionamento Físico Animal , Animais , Coração , Masculino , Nandrolona/farmacologia , Ratos , Ratos Wistar , Remodelação Ventricular
12.
Phytother Res ; 35(8): 4425-4432, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33969554

RESUMO

The drastic decrease in estrogen levels in menopausal women can elevate bone resorption and osteoporosis. Cornus mas extract (C. mas extract) is a potential candidate for treating menopausal-related bone complications because of its phytoestrogen and anti-inflammatory contents. It was an interventional double-blind placebo-controlled randomized study. Eighty-four women aged 45-60 years old were randomly allocated to either the extract group receiving 3 capsules of 300 mg C. mas extract or the placebo group receiving 3 capsules of 300 mg of starch powder per day for 8 weeks. Then, venous blood was used to measure bone-specific alkaline phosphatase (BAP), osteocalcin (OC), C-terminal telopeptide (TC) as well as serum levels of PTH and hsCRP. Our results indicated the decrease in alkaline phosphatase, PTH, and as an inflammation biomarker, hsCRP, between two groups at the end of the study. No statistically significant difference was observed in telopeptide C, osteocalcin, and calcium between the placebo and extract groups after 8 weeks of intervention. In conclusion, the results indicate that the C. mas extract supplement of 900 mg/day may decrease levels of BAP, PTH, and hsCRP. However, this intervention had no beneficial effect on OC and TC in healthy postmenopausal women.


Assuntos
Cornus , Osteoporose Pós-Menopausa , Extratos Vegetais , Fosfatase Alcalina/sangue , Biomarcadores , Densidade Óssea , Colágeno Tipo I/sangue , Cornus/química , Método Duplo-Cego , Feminino , Humanos , Inflamação/tratamento farmacológico , Pessoa de Meia-Idade , Osteocalcina/sangue , Osteoporose Pós-Menopausa/tratamento farmacológico , Peptídeos/sangue , Extratos Vegetais/farmacologia , Pós-Menopausa
13.
Iran J Basic Med Sci ; 24(10): 1388-1394, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35096297

RESUMO

OBJECTIVES: Atorvastatin (AT), a competitive inhibitor of 3-hydroxymethyl-3-glutaryl-coenzyme-A reductase, is a cholesterol-lowering drug. AT has been shown to have neuroprotective, antioxidant, and anti-inflammatory properties. Previously, we have reported that AT could attenuate the behavioral, renal, and hepatic manifestations of aging. To clarify further the mechanisms involved, the present study was designed to evaluate the effect of AT on the expression of some aging-related genes in the brain of aging mice induced by D-galactose (DG). MATERIALS AND METHODS: For this purpose, AT (0.1 and 1 mg/kg/p.o.) was administrated daily in DG-received (500 mg/kg/p.o.) mice model of aging for six weeks. At the end of the experiment, mice were decapitated to remove the brains. Then, the expression profiles of sirtuin 1 (Sirt1), P53, P21, Bcl-2, Bax, superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), interleukin 1 beta (IL1ß), tumor necrosis factor-alpha (TNFα), inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and brain-derived neurotrophic factor (BDNF) were assessed using the real-time PCR method. RESULTS: The present study shows that DG decreases the expression of Sirt1, Bcl-2, CAT, GPx, and BDNF while increasing the expression of P53, P21, Bax, IL-1ß, iNOS, COX-2, and TNF-α. According to the findings of the present study, AT (more potentially at the dose of 1 mg/kg) modulates the expression of these aging-related genes in the brain of aging mice. CONCLUSION: The results of the present study confirmed our previous reports on the anti-aging effects of AT at the gene level, the precise mechanisms and underlying pathways need further studies.

14.
Fundam Clin Pharmacol ; 35(1): 113-130, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32579730

RESUMO

Abuse of alcohol triggers neurodegeneration in human brain. Minocycline has characteristics conferring neuroprotection. Current study evaluates the role of the CREB-BDNF signaling pathway in mediating minocycline's neuroprotective effects against alcohol-induced neurodegeneration. Seventy adult male rats were randomly split into groups 1 and 2 that received saline and alcohol (2 g/kg/day by gavage, once daily), respectively, and groups 3, 4, 5, and 6 were treated simultaneously with alcohol and minocycline (10, 20, 30 and 40 mg/kg I.P, respectively) for 21 days. Group 7 received minocycline alone (40 mg/kg, i.p) for 21 days. Morris water maze (MWM) has been used to assess cognitive activity. Hippocampal neurodegenerative and histological parameters as well as cyclic AMP response element-binding protein (CREB) and brain-derived neurotrophic factor (BDNF) levels were assessed. Alcohol impaired cognition, and concurrent therapy with various minocycline doses attenuated alcohol-induced cognition disturbances. Additionally, alcohol administration boosted lipid peroxidation and levels of glutathione in oxidized form (GSSG), tumor necrosis factor alpha (TNF-α), interleukin 1 beta (IL-1ß), and Bax protein, while decreased reducing type of glutathione (GSH), Bcl-2 protein, phosphorylated CREB, and BDNF levels in rat hippocampus. Alcohol also decreased the activity in the hippocampus of superoxide dismutase (SOD), glutathione peroxidase (GPx), and glutathione reductase (GR). In comparison, minocycline attenuated alcohol-induced neurodegeneration; elevating expression levels of P-CREB and BDNF and inhibited alcohol induced histopathological changes in both dentate gyrus (DG) and CA1 of hippocampus. Thus, minocycline is likely to provide neuroprotection against alcohol-induced neurodegeneration through mediation of the P-CREB/BDNF signaling pathway.


Assuntos
Fator Neurotrófico Derivado do Encéfalo/fisiologia , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/fisiologia , Etanol/toxicidade , Minociclina/farmacologia , Doenças Neurodegenerativas/prevenção & controle , Fármacos Neuroprotetores/farmacologia , Animais , Glutationa/metabolismo , Hipocampo/efeitos dos fármacos , Hipocampo/patologia , Masculino , Teste do Labirinto Aquático de Morris , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Wistar , Transdução de Sinais/fisiologia
15.
Nanomedicine ; 31: 102319, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33068745

RESUMO

The goal of this study was to develop a new method based on Oncothermia with concomitant use of the temozolomide (TMZ)-loaded magnetic nanoparticles conjugated with folic acid (TMZ/MNPs-FA) and alternative magnetic field (AMF) and evaluate its efficacy in the treatment of C6 glioma in rats. TMZ/MNPs-FA were prepared and evaluated for their size, surface charge, magnetic saturation, hemolysis and in vitro AMF-triggered release. The glioma rat models were treated with free TMZ, MNPs-FA and TMZ/MNPs-FA in the presence or absence of AMF (43 °C). The results confirmed that a combinatorial therapy consisting of AFM hyperthermia and thermosensitive TMZ/MNPs-FA could significantly suppress tumor growth, increase survival rate and promote apoptosis (P < 0.0001). Therefore, this treatment strategy may be a powerful modality for treatment of cancer, as the thermal and mechanical effects of magnetic nanoparticles exposed to AMF can increase the therapeutic efficacy of conventional chemotherapy.


Assuntos
Glioma/tratamento farmacológico , Campos Magnéticos , Nanopartículas de Magnetita/química , Animais , Ácido Fólico/uso terapêutico , Ratos , Temozolomida/uso terapêutico
16.
Iran J Basic Med Sci ; 23(5): 606-615, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32742598

RESUMO

OBJECTIVES: Present study investigated the neuroprotective effects of selegiline and the molecular mechanisms involved in methamphetamine-induced neurotoxicity. MATERIALS AND METHODS: Male wistar rats were randomly divided into six groups (10 rats in each group). Group 1 and group 2 received normal saline and methamphetamine (10 mg/kg), respectively. Groups 3, 4, 5 and 6 were treated simultaneously with methamphetamine and selegiline. From day 22 to day 28, forced swim test, elevated plus maze, and open field test were conducted to assess mood (anxiety and depression) levels, and from day 17 to day 21, Morris Water Maze was conducted for cognition assessment. On day 29, hippocampus of the animals were isolated and evaluated by ELISA method for oxidative, antioxidant, and inflammatory factors and expression levels of active (total) and inactive (phosphorylated) forms of cyclic AMP response element binding protein (CREB), brain-derived neurotrophic factor (BDNF), Akt (Protein Kinase B) and glycogen synthase kinase 3 (GSK3) proteins. RESULTS: Selegiline reduced behavioral impacts caused by methamphetamine in all doses. Methamphetamine administration may improve malondialdehyde, tumor necrosis factor-alpha, interleukin-1 beta and GSK3 (both forms). Moreover, methamphetamine reduced the activity of superoxide dismutase, glutathione peroxidase, glutathione reductase, amount of BDNF, CREB and Akt (both forms). CONCLUSION: Current research showed that selegiline can protect the brain from methamphetamine-prompted neurodegeneration, and this could be intervened by CREB -BDNF or Akt-GSK3 signaling pathways.

17.
Behav Brain Res ; 386: 112597, 2020 05 27.
Artigo em Inglês | MEDLINE | ID: mdl-32198107

RESUMO

AIM: Neurodegeneration is one of the serious adverse effects of stimulant agents such as nicotine. Minocycline possess established neuroprotective properties. The role of CREB-BDNF signaling pathway in mediating the neuroprotective effects of minocycline against nicotine-induced neurodegeneration in rats was evaluated in current study. METHODS: Seventy adult male rats were divided randomly into seven groups. Group 1 and 2, received 0.7 ml/rat of normal saline (i.p) and nicotine (10 mg/kg, s.c) respectively. Groups 3, 4, 5 and 6, treated concurrently with nicotine (10 mg/kg) and minocycline (10, 20, 30 and 40 mg/kg, i.p, respectively) for 21 days. Group 7 received minocycline alone (40 mg/kg, i.p) for 21 days. From 17th to 21 st days of experiment, Morris water maze (MWM) was used to evaluate learning and spatial memory in rats treated in different groups. According to the critical role of hippocampus in cognitive behavior, hippocampal neurodegenerative parameters (oxidative stress and inflammatory biomarkers) and also cyclic AMP response element binding protein (CREB) and brain-derived neurotrophic factor (BDNF) levels were evaluated in isolated hippocampus in day 22 of experiment and after drug treatment. Also hippocampal cell density and tissue changes were evaluated by hematoxylin and eosin staining. RESULT: Nicotine administration impaired the learning and spatial memory in rats and simultaneous treatment with various doses of minocycline attenuated the nicotine-induced cognition disturbances. In addition, nicotine treatment increased lipid peroxidation and the levels of oxidized form of glutathione (GSSG), interleukin 1 beta (IL-1ß), tumor necrosis factor alpha (TNF-α), and Bax protein, while decreasing reduced form of glutathione (GSH), Bcl-2 protein, P-CREB and BDNF levels in the hippocampus of experimental animals. Nicotine also reduced the activity of superoxide dismutase (SOD), glutathione peroxidase (GPx) and glutathione reductase (GR) in the hippocampus. Minocycline attenuated nicotine-induced neurodegeneration and elevating CREB (both forms) and BDNF levels. Also minocycline treatment alone increases the cognitive activity and increased CREB (both forms) and BDNF levels and decreased oxidative stress, inflammation and apoptotic biomarkers. Minocycline at high doses cause inhibition of nicotine induced cell density and changes in both area of dentate gyrus (DG) and CA1 in hippocampus. CONCLUSION: It can be concluded that minocycline, probably through activation of P-CREB/BDNF signaling pathway, confers neuroprotection against nicotine-induced neurodegeneration in rat hippocampus.


Assuntos
Disfunção Cognitiva/tratamento farmacológico , Minociclina/farmacologia , Nicotina/efeitos adversos , Animais , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Cognição/efeitos dos fármacos , Disfunção Cognitiva/prevenção & controle , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Glutationa/metabolismo , Glutationa Peroxidase/metabolismo , Glutationa Redutase/metabolismo , Hipocampo/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Minociclina/metabolismo , Doenças Neurodegenerativas/tratamento farmacológico , Doenças Neurodegenerativas/fisiopatologia , Neuroproteção/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Nicotina/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Wistar , Transdução de Sinais/efeitos dos fármacos , Superóxido Dismutase/metabolismo
18.
J Photochem Photobiol B ; 205: 111827, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32120183

RESUMO

5-iodo-2-deoxyuridine (IUdR) has been demonstrated to induce an appreciable radiosensitizing effect on glioblastoma patients, but due to the short circulation half-life times and failure to pass through the blood-brain barrier (BBB), its clinical use is limited. Accordingly, in this study, we used magnetic graphene oxide (NGO/SPIONs) nanoparticles coated with PLGA polymer as a dynamic nanocarrier for IUdR and, evaluated its sensitizing enhancement ratio in combination with a single dose X-ray at clinically megavoltage energies for treatment of C6 glioma rats. Nanoparticles were characterized using Zetasizer and TEM microscopy, and in vitro biocompatibility of nanoparticles was assessed with MTT assay. IUdR/MNPs were intravenously administered under a magnetic field (1.3 T) on day 13 after the implantation of C6 cells. After a day following the injection, rats exposed with radiation (8 Gy). ICP-OES analysis data indicated an effective magnetic targeting, leading to remarkably improved penetration through the BBB. In vivo release analysis with HPLC indicated sustained release of IUdR and, prolonged the lifespan in plasma (P < .01). In addition, our findings revealed a synergistic effect for IUdR/MNPs coupled with radiation, which significantly inhibited the tumor expansion (>100%), prolonged the survival time (>100%) and suppressed the anti-apoptotic response of glioma rats by increasing Bax/Bcl-2 ratio (2.13-fold) in compared with the radiation-only. In conclusion, besides high accumulation in targeted tumor sites, the newly developed IUdR/MNPs, also exhibited the ability of IUdR/MNPs to significantly enhance radiosensitizing effect, improve therapeutic efficacy and increase toxicity for glioma-bearing rats.


Assuntos
Neoplasias Encefálicas/tratamento farmacológico , Glioma/tratamento farmacológico , Grafite/administração & dosagem , Idoxuridina/administração & dosagem , Nanopartículas/administração & dosagem , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/administração & dosagem , Radiossensibilizantes/administração & dosagem , Animais , Encéfalo/metabolismo , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patologia , Linhagem Celular Tumoral , Liberação Controlada de Fármacos , Glioma/metabolismo , Glioma/patologia , Grafite/química , Grafite/farmacocinética , Concentração de Íons de Hidrogênio , Idoxuridina/farmacocinética , Fenômenos Magnéticos , Masculino , Nanopartículas/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/farmacocinética , Coelhos , Radiossensibilizantes/farmacocinética , Ratos Wistar , Carga Tumoral/efeitos dos fármacos
19.
Iran J Allergy Asthma Immunol ; 19(6): 602-611, 2020 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-33463129

RESUMO

The T-cell immunoglobulin and mucin-3 (TIM-3)/galectin-9 (Gal-9) autocrine loop is an indispensable signaling in acute myeloid leukemia (AML) cells, which induces their self-renewal through activation of nuclear factor-kappa b (NF-kB) and ß-catenin pathways. In this study, we evaluated the effects of oridonin and doxorubicin on the TIM-3/Gal-9 autocrine loop. We also evaluated oridonin anti-inflammatory and anti-cancer properties on U937 cells, as an AML cell line in comparison to doxorubicin as a common anthracycline drug for AML treatment. Cell counting kit-8 (CCK-8) was applied to evaluate the cytotoxicity of oridonin and doxorubicin on U937 cells and also to determine the impact of galectin-9 (Gal-9) on their proliferation. The effects of oridonin and doxorubicin on Gal-9, TIM-3, and interleukin-1ß (IL-1ß) gene expression were determined by real-time polymerase chain reaction (RT-PCR). The Gal-9 secretion level was measured by enzyme-linked immunosorbent assay (ELISA) and activation of NF-kB pathway was assessed by western blotting. In a dose-dependent manner, oridonin and doxorubicin were capable to eradicate U937 cells while Gal-9 expanded them. Following the treatment of U937 cells with oridonin, the expression of Gal-9, TIM-3, and IL-1ß genes was down-regulated, and the Gal-9 secretion and NF-kB phosphorylation were diminished, whereas doxorubicin increased all of these factors. Doxorubicin is a common treatment agent in AML, but it may induce inflammation and up-regulate the TIM3/Gal-9 autocrine loop, consequently can enhance the possibility of disease relapse. Meanwhile, oridonin is capable to inhibit the essential signaling pathways in AML cells and reduce the inflammation and expansion of tumor cells and postpone AML recurrence.


Assuntos
Diterpenos do Tipo Caurano/farmacologia , Galectinas/metabolismo , Receptor Celular 2 do Vírus da Hepatite A/metabolismo , Imunoglobulinas/metabolismo , Inflamação/tratamento farmacológico , Leucemia Mieloide Aguda/tratamento farmacológico , Linfócitos T/efeitos dos fármacos , Linhagem Celular Tumoral , Doxorrubicina , Humanos , Inflamação/metabolismo , Leucemia Mieloide Aguda/metabolismo , NF-kappa B/metabolismo , Transdução de Sinais/efeitos dos fármacos , Linfócitos T/metabolismo , Células U937
20.
Acta Neurobiol Exp (Wars) ; 79(4): 352-366, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31885392

RESUMO

Methylphenidate (MPH) abuse causes adverse neurobehavioral and neurochemical effects. Some herbal components such as crocin have shown neuroprotective properties. The current study evaluates the potential role of the cyclic AMP response element binding protein (CREB)­brain­derived neurotrophic factor (BDNF) signaling pathway in mediating the neuroprotective effects of crocin against MPH­induced neurotoxicity in rats. Seventy adult male rats were randomly divided into seven groups. Group 1 and 2 received 0.7 ml/rat of normal saline and 10 mg/kg of MPH, respectively. Groups 3, 4, 5, and 6 were treated simultaneously with MPH (10 mg/kg) and crocin (10, 20, 40, and 80 mg/kg, respectively) for 21 days. Group 7 was treated with crocin (80 mg/kg) alone for 21 days. The Morris water maze (MWM) and open field test were used to assess cognitive and locomotor activities. Hippocampal neurotoxicity parameters and levels of BDNF and CREB were evaluated. Simultaneous treatment with various doses of crocin reduced the MPH­induced cognition disturbances and hyperlocomotion. In addition, lipid peroxidation increased with MPH treatment and levels of the oxidized forms of glutathione (GSSG), interleukin 1 beta (IL­1ß), tumor necrosis factor alpha (TNF­α), and Bax increased. MPH treatment decreased levels of the reduced form of glutathione (GSH), P­CREB, Bcl­2, and BDNF in the hippocampus. MPH also reduced activity of superoxide dismutase, glutathione peroxidase, and glutathione reductase in the hippocampus. In contrast, crocin attenuated MPH­induced oxidative stress, inflammation, and apoptosis, and increased levels of P­CREB and BDNF. Thus, crocin - likely via stimulation of the P­CREB/BDNF signaling pathway - displayed neuroprotection against MPH­induced neurotoxicity.


Assuntos
Fator Neurotrófico Derivado do Encéfalo/fisiologia , Carotenoides/uso terapêutico , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/fisiologia , Hipocampo/efeitos dos fármacos , Intoxicação por MPTP/tratamento farmacológico , Proteínas do Tecido Nervoso/fisiologia , Fármacos Neuroprotetores/uso terapêutico , Transdução de Sinais/efeitos dos fármacos , Animais , Fator Neurotrófico Derivado do Encéfalo/biossíntese , Fator Neurotrófico Derivado do Encéfalo/genética , Carotenoides/farmacologia , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/biossíntese , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/genética , Comportamento Exploratório , Glutationa/metabolismo , Glutationa Peroxidase/metabolismo , Glutationa Redutase/metabolismo , Hipocampo/metabolismo , Peroxidação de Lipídeos , Masculino , Aprendizagem em Labirinto , Proteínas do Tecido Nervoso/biossíntese , Proteínas do Tecido Nervoso/genética , Fármacos Neuroprotetores/farmacologia , Oxirredução , Proteínas Proto-Oncogênicas c-bcl-2/biossíntese , Proteínas Proto-Oncogênicas c-bcl-2/genética , Distribuição Aleatória , Ratos , Ratos Wistar , Transdução de Sinais/fisiologia , Superóxido Dismutase/metabolismo , Natação , Proteína X Associada a bcl-2/biossíntese , Proteína X Associada a bcl-2/genética
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