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1.
Biochem Genet ; 2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38536569

RESUMO

Non-alcoholic fatty liver disease is a multifactorial disorder with complicated pathophysiology ranging from simple steatosis to steatohepatitis and liver fibrosis. Trimethylamine-N-oxide (TMAO) production is believed to be correlated with choline deficiency. This study investigated the expression of miRNA-34a, miRNA-122, and miRNA-192 in the fatty liver cell model treated with different concentrations of TMAO. A fatty liver cell model was developed by exposing HepG2 cells to a mixture of palmitate and oleate in a ratio of 1:2 at a final concentration of 1200 µM for 24 h. The confirmed fatty liver cells were treated with 37.5, 75, 150, and 300 µM of TMAO for 24 h. RT-qPCR was used to quantify the expression of microRNAs in a cellular model. The cellular expression of all microRNAs was significantly higher in treated fatty liver cells compared to normal HepG2 cells (P < 0.05). Only 75 and 150 µM of TMAO significantly increased the expression of miRNA-34a and miRNA-122 compared to both fatty and normal control cells (P < 0.05). Our results provided an experimental documentation for the potential effect of TMAO to change the expression of miR-34a and miR-22 as a mechanism for contributing to the pathogenesis of non-alcoholic fatty liver disease.

2.
Cell J ; 25(7): 461-469, 2023 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-37543859

RESUMO

OBJECTIVE: This study aimed to compare the effect of different physical training on the mechanism of ceramidedependent insulin resistance in the flexor hallucis longus (FHL) muscle of diabetic rats. MATERIALS AND METHODS: In this experimental study, 7 healthy as a healthy control (HC) group, and 21 diabetics (55 mg/ kg Streptozotocin) Wistar rats (200-220 g; 8-10 weeks old) divided into the diabetic control (DC), moderate continuous training (MCT), and moderate intensity interval training (MIIT) groups. Both MCT (55-70% of maximal oxygen uptake (VO2max), and MIIT (85% VO2max) groups trained for 10-25 minutes at a speed of 10-20 m/minutes. The changes in the expression of blood glucose, insulin, insulin resistance, lipid profile and total ceramide were measured as well as ceramide synthase-1, Glucose transporter type 4 (GLUT4), Protein kinase B known as Akt, phosphorylated protein kinase B known as pAkt, protein kinase C (PKC), and tumour necrosis factor α (TNFα). RESULTS: Blood glucose, triglyceride (TG) and ceramide synthase-1 (CS1) expression levels in the MCT group decreased in comparison with the DC group. FHL protein expression of GLUT4 in the MCT group was higher than the DC group. FHL expression of GLUT4, pAKT, AKT/pAKT, PKC, CS1 and total ceramide in the MIIT group were higher than the DC group. Cholesterol, low-density lipoprotein (LDL), TG, and TNF-α protein expression in the MIIT group were lower than the DC group. GLUT4, PKC, pAKT, AKT/pAKT in the MIIT group were higher, and total ceramide and TNF-α were lower in the MIIT group than the MCT group. CONCLUSION: It seems that both training plan MIIT and MCT have favorable effects on the metabolism of glucose, insulin, lipids, and the decrease of TNFα level in the diabetes, but in connection with the improvement of the ceramides mechanism, it seems that the MIIT training plan is more optimal than MCT training plan.

3.
Neurochem Res ; 48(7): 2187-2195, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-36856963

RESUMO

Temporal lobe epilepsy (TLE) is the most common form of partial and drug-resistant epilepsy, characterized by recurrent seizures originating from temporal lobe structures like the hippocampus. Hippocampal sclerosis and oxidative stress are two important factors in the pathogenesis of TLE that exacerbate epileptic seizures in this form of epilepsy. Recently, royal jelly (RJ) shown to have neuroprotective and antioxidant activities in several neurodegenerative models. Therefore, the aim of the present study was to investigate the pretreatment effect of RJ on epileptic seizures, hippocampal neuronal loss, and oxidative stress in the rat model of kainic acid (KA)-induced TLE. To this aim, 40 male Wistar rats weighing 200-250 g were divided into 4 groups, including control, vehicle, KA, and RJ + KA. Rats received RJ (150 mg/kg/day) for 14 days before induction of TLE with KA. Epileptic behaviors were evaluated according to Racine's scale. Oxidative stress markers including, malondialdehyde (MDA), total oxidant status (TOS) and total antioxidant capacity (TAC) as well as neuronal loss in the CA1 region of the hippocampus (using Nissl staining) were evaluated in all groups. Our findings showed that RJ pretreatment significantly reduced the seizure score and increased the latency to the first seizure. RJ also reduced MDA and TOS while increasing TAC. In addition, RJ reversed neuronal damage in the hippocampal CA1 and CA3 areas. In conclusion, our results suggest that RJ has anticonvulsant and neuroprotective effects in KA induced TLE via its antioxidative properties.


Assuntos
Epilepsia do Lobo Temporal , Epilepsia , Animais , Masculino , Ratos , Anticonvulsivantes , Antioxidantes , Modelos Animais de Doenças , Epilepsia/tratamento farmacológico , Epilepsia do Lobo Temporal/induzido quimicamente , Epilepsia do Lobo Temporal/tratamento farmacológico , Epilepsia do Lobo Temporal/patologia , Hipocampo , Ácido Caínico/toxicidade , Ratos Wistar , Convulsões/induzido quimicamente , Convulsões/tratamento farmacológico , Convulsões/patologia
4.
Neurochem Res ; 48(6): 1775-1782, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36689085

RESUMO

Huntington's disease (HD) is a progressive, neurodegenerative, and inherited disease. Antioxidants have been shown to be effective in slowing disease progression in animal models of HD and are under investigation in human clinical trials. α-pinene, a member of the monoterpene class, has been shown to exert antioxidant activity. Therefore, this study aimed to investigate the impact of α-pinene on animal model of HD. Thirty-two male Wistar rats received 3-Nitropropionic acid (3-NP) for induction of the disease model or treated with α-pinene + 3-NP in different groups. Motor skill, and biochemical evaluations to detect oxidant/antioxidant markers in rat cortex and striatum were performed in all groups. We found that α-pinene significantly improved 3-NP-induced changes in the body weight, rotarod activity, time taken to cross the narrow beam, and locomotor activity. Biochemical analysis revealed that α-pinene significantly decreased the 3NP-induced elevation in oxidant markers, nitrite, and malondialdehyde in both cortex and striatum. In addition, α-pinene counteracted the 3-NP-induced fall in antioxidant enzymes, including superoxide dismutase, catalase, and glutathione in the cortex and striatum. In conclusion, we found that α-pinene prevented the motor dysfunction induced by 3-NP in the animal model of Huntington's disease. Oxidants-antioxidant balance might be involved in the protective effect of α-pinene.


Assuntos
Doença de Huntington , Fármacos Neuroprotetores , Humanos , Ratos , Masculino , Animais , Antioxidantes/farmacologia , Ratos Wistar , Doença de Huntington/induzido quimicamente , Doença de Huntington/tratamento farmacológico , Atividade Motora , Peroxidação de Lipídeos , Modelos Animais , Oxidantes , Nitrocompostos/farmacologia , Modelos Animais de Doenças , Fármacos Neuroprotetores/uso terapêutico , Comportamento Animal
5.
Life Sci ; 311(Pt A): 121156, 2022 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-36356894

RESUMO

BACKGROUND: Triple-negative breast cancer (TNBC) is the most aggressive type of cancer without any approved targeted therapy. Epigenetic processes have a pivotal role in cancer cell progression and while histone deacetylase 8 (HDAC8) has been proven as a potential oncogene in breast cancer, its underlying molecular mechanism is not known. Therefore, the present study, aimed to evaluate the underlying mechanism of the HDAC8 carcinogenesis in breast cancer progression. METHODS: The potential role of HDAC8 in cancer cell processes such as apoptosis, invasion, migration, angiogenesis, and cancer stem cells (CSCs) markers were evaluated by using flow cytometry Annexin V-FITC/propidium iodide (PI), reverse transcription-polymerase chain reaction (RT-qPCR), Matrigel-coated transwell plates and wound healing assay on both cell lines. The impact of HDAC8 on tumor development was also studied using a breast cancer xenograft model. RESULTS: HDAC8 expression was significantly downregulated in the cell lines, post-transfection with KO-vector. Downregulation of HDAC8 dramatically decreased cell migration, angiogenesis, and invasion while inducing apoptosis in MDAMB-468 and MDA-MB-231 cell lines. HDAC8 knocked out TNBC cell lines had lower levels of cancer stemness markers, such as prominin-1 (CD133), CD44, BMI1, and Aldehyde dehydrogenase 1 (ALDH1). Additionally, the knockout of HDAC8 inhibited tumor growth in a breast cancer xenograft model. CONCLUSION: The findings show that knocking out HDAC8 retains several anticancer actions in BC cells, such as inducing apoptosis, reducing migration, invasion, angiogenesis and removing CSCs markers.


Assuntos
Neoplasias de Mama Triplo Negativas , Humanos , Neoplasias de Mama Triplo Negativas/patologia , Linhagem Celular Tumoral , Deleção de Genes , Histona Desacetilases/genética , Histona Desacetilases/metabolismo , Células-Tronco Neoplásicas/metabolismo , Proteínas Repressoras/genética
6.
Mol Biol Rep ; 49(7): 5927-5937, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35348964

RESUMO

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is a multifactorial disorder with complicated pathophysiology. Trimethylamine-N-oxide (TMAO) has been thought to be correlated with the pathogenesis of NAFLD. The single nucleotide polymorphisms (SNPs) of hepatic flavin-containing monooxygenase 3 (FMO3) regulate the concentration of TMAO. This case-control study investigated the plasma levels of TMAO as well as its possible correlation with the frequency of specific genotype of FMO3 (-2650C>G, -2543T>A, -2177G>C, -2589C>T, -2106G>A polymorphisms) in Kurdish patients with NAFLD. METHODS AND RESULTS: In 85 confirmed NAFLD patients and 30 healthy individuals, triglycerides (TG), total cholesterol (Chol), low-density lipoprotein (LDL), high-density lipoprotein (HDL), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) activities were measured. TMAO was also measured using the LC-MS/MS method. High-resolution melting analysis was applied to determine FMO3 genotypes. Plasma TMAO levels were significantly higher in patients (p = 0.030). A CC genotype with a frequency of 12.9% for SNP -2177G>C was found in Kurdish NAFLD patients. The distribution of the GC genotype was also significantly different (p = 0.017). CONCLUSIONS: The current results provide documentation for high circulatory levels of TMAO and its possible correlation with the presence of the specific genotype -2177G>C FMO3 in Kurdish NAFLD patients.


Assuntos
Hepatopatia Gordurosa não Alcoólica , Estudos de Casos e Controles , Cromatografia Líquida , Flavinas , Humanos , Metilaminas , Oxigenases de Função Mista , Hepatopatia Gordurosa não Alcoólica/genética , Óxidos , Oxigenases , Espectrometria de Massas em Tandem
7.
J. physiol. biochem ; 78(1): 185-197, feb. 2022.
Artigo em Inglês | IBECS | ID: ibc-215882

RESUMO

Nonalcoholic fatty liver disease (NAFLD) is a common chronic liver disease that is rapidly becoming a public health problem. An imbalance in lipid distribution to the hepatocytes and metabolism causes hepatocyte steatosis. Vaspin is a newly discovered adipokine that has been linked to a variety of metabolic disorders. The effects of vaspin on steatosis and fibrosis pathogenesis and related mechanisms are unclear. Thus, this study investigated the molecular mechanism of vaspin on hepatocyte steatosis and fibrosis. HepG2 cells were treated with 1.2 mM free fatty acid and the intracellular lipid values were measured by flow cytometry and Nile red assay. RT-qPCR was used to assess the effect of vaspin and blocking of the GRP78 receptor on the expression of lipogenesis, oxidation, uptake, and secretion of fatty acid (FA), as well as AMPK activity. In co-cultured HepG2 and LX-2 cell lines, the expression of main proteins of hepatocyte fibrosis was analyzed using Western blot analysis. In the HepG2 cell line, we discovered that vaspin increased oxidation, FA secretion and gene expression, and AMPK activity and decreased lipogenesis and FA uptake and gene expression. Western blot analysis in co-cultured HepG2 and LX-2 cell lines showed that α-SMA and TGF-β1 protein expression decreased. The data demonstrated that vaspin acts as a novel regulator of hepatocyte steatosis through the GRP78 receptor, effectively reducing hepatocyte fibrosis through AMPK activation and decreasing NF-κB gene expression. (AU)


Assuntos
Humanos , Animais , Camundongos , Serpinas , Hepatopatia Gordurosa não Alcoólica , Proteínas Quinases Ativadas por AMP , Adipocinas , Fibrose , Hepatócitos/metabolismo , Fígado/metabolismo , Camundongos Endogâmicos C57BL
8.
Inflammopharmacology ; 30(1): 283-290, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35022915

RESUMO

Ulcerative colitis (UC), limited to the colon's innermost lining, has become a global health problem. Immunomodulatory and monoclonal antibodies are used to treat UC despite their side effects and limitations. Phenytoin is used to heal wounds owing to its effects on growth factors, collagen, and extracellular matrix synthesis. This study aimed to evaluate the effect of topical phenytoin administration in UC. Phenytoin was administered in two doses during the treatment. Eighty male Wistar rats (230-280 g) were divided randomly into ten groups of sham, control, hydrocortisone, phenytoin 1%, and 3% groups in 6- or 12-day treatment protocols. The UC model was induced by the administration of acetic acid 4% into the colon. Animals were killed on the 7th and 13th postoperative days. The main outcome measures included body weight loss, microscopic score, and ulcer index measured using specific criteria. Growth factors were measured by western blotting. Results illustrated that body weight loss was reversed in the treatment groups. Ulcer index had decreased on 6- and 12-day treatment protocols. Microscopic scores in 6-day enema treatment significantly decreased compared to the control groups. Transforming growth factor-beta (TGFß) significantly increased in a time-dependent manner and platelet-derived growth factor (PDGF) and vascular endothelial growth factor (VEGF) significantly increased in a time- and dose-dependent manner in phenytoin 1% and 3% in the 6- and 12-day protocols. Phenytoin dose- and time-dependently reversed weight loss. In addition, histopathological parameters included microscopic scores, and the ulcer index was decreased through the induction of growth factors TGFß, PDGF, and VEGF and consequently accelerated ulcer healing.


Assuntos
Colite Ulcerativa , Fator de Crescimento Derivado de Plaquetas , Ácido Acético , Animais , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/tratamento farmacológico , Masculino , Fenitoína/efeitos adversos , Fator de Crescimento Derivado de Plaquetas/efeitos adversos , Ratos , Ratos Wistar , Fator de Crescimento Transformador beta , Fatores de Crescimento Transformadores/efeitos adversos , Fator A de Crescimento do Endotélio Vascular
9.
J Physiol Biochem ; 78(1): 185-197, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35001345

RESUMO

Nonalcoholic fatty liver disease (NAFLD) is a common chronic liver disease that is rapidly becoming a public health problem. An imbalance in lipid distribution to the hepatocytes and metabolism causes hepatocyte steatosis. Vaspin is a newly discovered adipokine that has been linked to a variety of metabolic disorders. The effects of vaspin on steatosis and fibrosis pathogenesis and related mechanisms are unclear. Thus, this study investigated the molecular mechanism of vaspin on hepatocyte steatosis and fibrosis. HepG2 cells were treated with 1.2 mM free fatty acid and the intracellular lipid values were measured by flow cytometry and Nile red assay. RT-qPCR was used to assess the effect of vaspin and blocking of the GRP78 receptor on the expression of lipogenesis, oxidation, uptake, and secretion of fatty acid (FA), as well as AMPK activity. In co-cultured HepG2 and LX-2 cell lines, the expression of main proteins of hepatocyte fibrosis was analyzed using Western blot analysis. In the HepG2 cell line, we discovered that vaspin increased oxidation, FA secretion and gene expression, and AMPK activity and decreased lipogenesis and FA uptake and gene expression. Western blot analysis in co-cultured HepG2 and LX-2 cell lines showed that α-SMA and TGF-ß1 protein expression decreased. The data demonstrated that vaspin acts as a novel regulator of hepatocyte steatosis through the GRP78 receptor, effectively reducing hepatocyte fibrosis through AMPK activation and decreasing NF-κB gene expression.


Assuntos
Hepatopatia Gordurosa não Alcoólica , Serpinas , Proteínas Quinases Ativadas por AMP/genética , Proteínas Quinases Ativadas por AMP/metabolismo , Adipocinas/metabolismo , Animais , Chaperona BiP do Retículo Endoplasmático , Fibrose , Células Hep G2 , Hepatócitos/metabolismo , Humanos , Metabolismo dos Lipídeos , Fígado/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Hepatopatia Gordurosa não Alcoólica/etiologia , Hepatopatia Gordurosa não Alcoólica/genética , Serpinas/genética , Serpinas/metabolismo , Serpinas/farmacologia , Transdução de Sinais
10.
Biol Trace Elem Res ; 200(7): 3265-3274, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34599428

RESUMO

Cerium oxide (CeO2) has potential applications in medicine and various consumer products. This study investigated the effect of CeO2 on the expression of genes associated with apoptosis and testicular development in mouse embryos. The experimental groups of pregnant mice were injected intraperitoneally with CeO2 at a concentration of 10 mg/kg on days 7 and 14 of pregnancy. Six days after birth, the testicles of neonatal male mice were collected for mRNA expression determination using real-time PCR, protein expression analysis by immunohistochemistry, and apoptotic cell population determination using the TUNEL assay. The results showed that the mRNA expression of the Bax, Caspase-3, and Gsk3-ß genes, unlike the Bcl2 gene, decreased significantly in the experimental group compared to the control group. The expression ratio of Bax/Bcl2 in the experimental group was lower than in the control group. A similar trend was observed in the population of apoptotic cells. In the experimental group, the expression levels of, Gata4, Sox8, and Rad54 at both the mRNA and protein levels increased significantly compared to the control group. Based on the results of this study, CeO2 at a concentration of 10 mg/kg, in addition to producing anti-apoptotic effects on the testicular cells of neonatal mice, can increase the expression of genes involved in testicular development and performance. The current experimental study proved the protective effects of 10 mg/kg CeO2 in developmental and apoptosis genes of testicular tissue in 6-day-old NMRI mice fetuses; however, more experiments are required to evaluate the possible side effects and interactions.


Assuntos
Cério , Nanopartículas Metálicas , Animais , Apoptose/genética , Cério/farmacologia , Feminino , Feto/metabolismo , Quinase 3 da Glicogênio Sintase/farmacologia , Masculino , Camundongos , Nanopartículas , Gravidez , Proteínas Proto-Oncogênicas c-bcl-2 , RNA Mensageiro/genética , Proteína X Associada a bcl-2/metabolismo
11.
Basic Clin Neurosci ; 13(1): 35-46, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36589015

RESUMO

Introduction: Probiotics, including lactobacilli, have immunomodulatory activities with promising effects on inflammatory diseases. In this study, we evaluate the effect of Enterococcus durans (Edu) and three various strains of lactobacilli (Lacto-mix), including L. rhamnosus, L. casei, and L. plantarum, to prevent Experimental Autoimmune Encephalomyelitis (EAE) features. Methods: C57BL/6 female mice were inoculated with Myelin Oigodendrocyte Glycoprotein (MOG35-55) in CFA (complete Freund's adjuvant) to induce EAE. Five groups (n=6 in each group) of animals received saline or probiotics by oral gavage with 200 µL of lactobacilli (1.5×108 CFU/mL) for 2 weeks before the immunization and during the test for one month. Results: Histopathological studies showed an increase in infiltration of inflammatory cells and destruction of the myelin membrane in the EAE group but a decrease in inflammatory cells in the probiotic-treated animals. Pro-inflammatory cytokines (Interleukin [IL]-17 and Interferon [IFN]-γ) concentration in the supernatant of the brain and spinal cord tissues showed a significant increase in the EAE compared with the normal saline group (P<0.01). While in the spinal cord tissue, there was a decrease in IL-17 in those animals treated with the Lactomix and Edu + Lacto-mix (P<0.01) and a significant decrease in IFN-γ in those animals that received Edu (P<0.05). Western blot analysis of matrix metalloproteinase-9 and myelin basic protein showed a decrease and increase in treatment and EAE groups, respectively, compared to the normal control group. Conclusion: Our data suggest that probiotic Enterococcus durans and Lacto-mix prevents EAE, but further studies are needed to clarify the exact mechanisms and their application in preclinical and clinical trials. Highlights: Dysfunction of the blood-brain barrier, migration of inflammatory cells into the Central Nervous System (CNS), and an increase in the pro-inflammatory factors, are the hallmarks in the pathogenesis of Multiple Sclerosis (MS) and Experimental Autoimmune Encephalomyelitis (EAE).The optimal effects of probiotic strains may involve the simultaneous use of more than one strain.Probiotic Enterococcus durans and Lacto-mix have a preventive effect against EAE. Plain Language Summary: Multiple Sclerosis (MS) is a myelin-degenerating autoimmune disease in the central nervous system. Experimental Autoimmune Encephalomyelitis (EAE), due to its similar clinical and pathologic features to MS, is widely used in many model studies of this disease. The microbiome refers to a genomic set of germs (bacteria, arches, fungi, and viruses), a commensal flora that lives in the intestine and niche of humans and other mammals. The microbiome affects the host's physiological system, especially the balance between health and disease. Additionally, the importance of the microbiome is evident in regulating the intestine-brain axis, or the coordination of the digestive and the central nervous system. In this regard, probiotics, including lactobacilli, have antioxidant and anti-inflammatory properties in vitro and in vivo. Probiotic strains have a wide range of health-improvement effects, and a combination of strains with specific properties provides a broader range of antimicrobial spectrum and stronger anti-inflammatory effects. Considering the critical role of probiotics in the immune system, this study aimed to investigate the possible role of Enterococcus durans alone or in combination with Lactobacillus mixture (L. rhamnosus, L. casei, and L. plantarum) on the EAE animal model of MS.

12.
Brain Res Bull ; 173: 184-192, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34051296

RESUMO

Parkinson's disease (PD) and diabetes mellitus share similar pathophysiological characteristics, genetic and environmental factors. It has been reported that people with diabetes mellitus appear to have a remarkable higher incidence of PD than age matched non diabetic individuals. Evidences suggest that use of antidiabetic glitazone is associated with a diminished risk of PD incidence in patients with diabetes. This study examined the effect of lobeglitazone, a member of thiazolidinedione class, in rat model of Parkinson's disease with diabetes co-morbidity. Rats received either rotenone and/or a combination of streptozocin and a high calorie diet for disease induction and they were treated with different doses of lobeglitazone or its vehicle. Behavioral tests comprising rotarod, bar test and rearing test were conducted to evaluate the motor function. Changes in the level tyrosine hydroxylase, TNF-α and NF-κB were analyzed using ELISA. In the same brain regions the possible changes in PPAR-γ receptor level were evaluated. Findings showed that although lobeglitazone tends to reverse the effect of rotenone in animals with diabetes, it was just able to prevent partly the motor defect in rearing test. Furthermore, lobeglitazone (1 mg/kg) reversed, in substantia nigra and striatum, the changes in tyrosine hydroxylase, TNF-α, NF-κB and PPAR-γ receptor content induced by rotenone in rats with diabetic condition. Although other preclinical studies are needed, these findings suggest that lobeglitazone is a promising neuroprotective candidate for clinical trials for PD patients with diabetes co-morbidity.


Assuntos
Diabetes Mellitus Experimental/fisiopatologia , Hipoglicemiantes/farmacologia , Atividade Motora/efeitos dos fármacos , Destreza Motora/efeitos dos fármacos , Doença de Parkinson Secundária/fisiopatologia , Pirimidinas/farmacologia , Tiazolidinedionas/farmacologia , Animais , Diabetes Mellitus Experimental/induzido quimicamente , Diabetes Mellitus Experimental/complicações , Modelos Animais de Doenças , Masculino , Doença de Parkinson Secundária/induzido quimicamente , Doença de Parkinson Secundária/complicações , Ratos , Ratos Wistar , Rotenona
13.
Avicenna J Phytomed ; 11(3): 302-313, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34046326

RESUMO

OBJECTIVE: Depression is one of the most common mood disorders. Considering the evidence on the effect of Cinnamomum on mood disorders, this study investigatedthe effect of hydroalcoholic extract of Cinnamomum (HEC) in an animal model of depression. MATERIALS AND METHODS: Thirty-two male rats were selected and divided into four groups (n=8) including: control, depressed, and depressed treated with200 and 400 mg/kg HEC. Depression induction protocol was conducted in all groups except for the control group. Sucrose preference test (SPT) and forced swimming test (FST) were done to analyze the depression score. After four weeks, the animals brain cortex was removed and BDNF protein and tyrosine receptor kinase B (TrkB) gene expression levels were determined by ELISA and Real Time PCR, respectively. RESULTS: The results of this study showed that 400 mg/kg of HEC increased the tendency to drink the sucrose solution. Furthermore, immobility time significantly increased in the depressed group compared to the control group while it was attenuated by administration of 400 mg/kg extract on the 28th day versus the depressed group. Also the extract at both doses increased swimming time compared to the depressed group. In addition, an increase in the BDNF protein and TrkB gene expression levels was observed in the prefrontal cortex of the treatment groups. CONCLUSION: We found that HEC ameliorated depression symptoms in rats and these effects were probably due to an increase in BDNF proteins and its receptor, TrkB, gene expressions in the prefrontal cortex.

14.
J Physiol Biochem ; 77(2): 331-339, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33635524

RESUMO

The unfolded protein response (UPR) plays a pivotal role in some exercise training-induced physiological adaptation. Our aim was to evaluate the changes in the protein kinase R-like endoplasmic reticulum kinase (PERK) arm of the UPR and hypertrophy signaling pathway following 8 weeks of resistance training and creatine (Cr) supplementation in rats. Thirty-two adult male Wistar rats (8 weeks old) were randomly divided into 4 groups of 8: untrained + placebo (UN+P), resistance training + placebo (RT+P), untrained + Cr (UN+Cr), and resistance training + Cr (RT+Cr). Trained animals were submitted to the ladder-climbing exercise training 5 days per week for a total of 8 weeks. Cr supplementation groups received creatine diluted with 1.5 ml of 5% dextrose orally. The flexor hallucis longus (FHL) muscle was extracted 48 h after the last training session and used for western blotting. After training period, the RT+Cr and RT+P groups presented a significant increase in phosphorylated and phosphorylated/total ratio hypertrophy indices, phosphorylated and phosphorylated/total ratio PERK pathway proteins, and other downstream proteins of the PERK cascade compared with their untrained counterparts (P < 0.05). The increase in hypertrophy indices were higher but PERK pathway proteins were lower in the RT-Cr group than in the RT+P group (P < 0.05). There was no significant difference between the untrained groups (P > 0.05). Our study suggests that resistance training in addition to Cr supplementation modifies PERK pathway response and improves skeletal muscle hypertrophy.


Assuntos
Creatina/administração & dosagem , Hipertrofia/genética , Músculo Esquelético/metabolismo , Condicionamento Físico Animal/métodos , Processamento de Proteína Pós-Traducional , Resposta a Proteínas não Dobradas , eIF-2 Quinase/genética , Fator 4 Ativador da Transcrição/genética , Fator 4 Ativador da Transcrição/metabolismo , Adaptação Fisiológica , Animais , Suplementos Nutricionais , Fator de Iniciação 2 em Eucariotos/genética , Fator de Iniciação 2 em Eucariotos/metabolismo , Hipertrofia/etiologia , Hipertrofia/metabolismo , Masculino , Fosforilação , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Ratos Wistar , Treinamento Resistido , Transdução de Sinais , Serina-Treonina Quinases TOR/genética , Serina-Treonina Quinases TOR/metabolismo , Fator de Transcrição CHOP/genética , Fator de Transcrição CHOP/metabolismo , eIF-2 Quinase/metabolismo
15.
Neurochem Res ; 46(6): 1372-1379, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33611726

RESUMO

Huntington's disease (HD) is a progressive, neurodegenerative and inherited disease and recent years have witnessed the understanding of the cellular and molecular mechanisms related to HD. Safranal, an organic compound isolated from saffron, has been reported to have anti-apoptotic, anti-inflammatory and antioxidant activity and has studied in chronic and neurodegenerative disease. Therefore, this study was aimed to investigate the effect of safranal on 3-NP induced locomotor activity and biochemical alterations in rats. To this aim, 40 male Wistar rats weighting 250-300 g were divided into 5 groups (n = 8) including sham, 3-NP group (10 mg/kg) as control and treatment groups (3-NP + safranal 0.75, 1.5 and 3 mg/kg) in two weeks duration of treatment. Behavioral/movement assessments in addition to oxidant/antioxidant markers in rat cortex and striatum were evaluated in control and treatment groups. Here, we found that safranal significantly alleviated 3-NP-induced changes of body weight, rotarod activity, number of vacuous chewing movements (VCMs), and locomotor activity. In addition, brain tissue assessments in cortex and striatum revealed that safranal could prevent the elevation of nitrite and malondialdehyde (MDA) levels as well as decrease of superoxide dismutase (SOD), catalase activity and glutathione (GSH) induced by 3-NP. In conclusion our results showed that safranal prevented the motor dysfunction induced by 3-NP in animal model of Huntington's disease. This effect might be due to its modulating effect on oxidants-antioxidant balance.


Assuntos
Antioxidantes/uso terapêutico , Cicloexenos/uso terapêutico , Doença de Huntington/tratamento farmacológico , Fármacos Neuroprotetores/uso terapêutico , Terpenos/uso terapêutico , Animais , Comportamento Animal/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Catalase/metabolismo , Córtex Cerebral/efeitos dos fármacos , Córtex Cerebral/enzimologia , Glutationa/metabolismo , Doença de Huntington/induzido quimicamente , Doença de Huntington/enzimologia , Locomoção/efeitos dos fármacos , Masculino , Malondialdeído/metabolismo , Mastigação/efeitos dos fármacos , Nitrocompostos , Propionatos , Ratos Wistar , Teste de Desempenho do Rota-Rod , Superóxido Dismutase/metabolismo
16.
Arab J Gastroenterol ; 22(1): 34-39, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32928706

RESUMO

BACKGROUND AND STUDY AIMS: Obstructive cholestasis increases the levels of oxidants and inflammatory mediators, leading to liver damage. Previous studies have found that Cichorium intybus possesses anti-inflammatory effects. In the present study, the effects of the hydroalcoholic extract of C. intybus leaves were assessed in a rat model of obstructive cholestasis. MATERIAL AND METHODS: Male Wistar rats were randomly divided into five groups (n = 6 rats per group): sham-operated, control [bile duct ligation (BDL) + vehicle)] and BDL + extract treatment (100, 200 and 400 mg/kg/day, i.p.) groups. Rats received treatments for 7 consecutive days. On the eighth day, prothrombin time (PT); serum albumin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase and total and direct bilirubin levels and total antioxidant and paraoxonase activities were measured using colorimetric methods. In addition, tumour necrosis factor-α and nitric oxide (NO) levels were measured using enzyme-linked immunosorbent assay. RESULTS: The hydroalcoholic extract of C. intybus significantly decreased PT and the serum levels of AST, ALT, TNF-α and NO compared with the control group (p < 0.05). On the other hand, the serum albumin levels were increased in the extract-treated groups compared with the control group (p < 0.05). CONCLUSION: The hydroalcoholic extract of C. intybus protects the liver against injury induced by obstructive cholestasis.


Assuntos
Colestase , Cichorium intybus , Animais , Colestase/complicações , Colestase/tratamento farmacológico , Ligadura , Fígado , Extratos Vegetais/farmacologia , Ratos , Ratos Wistar
17.
Adv Biomed Res ; 8: 56, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31673529

RESUMO

BACKGROUND: Ulcerative colitis (UC) is an inflammatory disease which is characterized by infiltration of inflammatory cells, crypt abscesses, distortion of the mucosal glands, and goblet cell depletion. The existence of neutrophil-rich inflammation in colon tissues of patients with UC is one of the most significant histological features of this disease. Nonetheless, the expression of CXCR chemokine receptors which appear as the main chemical mediators governing the migration of neutrophils into the mucosal tissue of patients with UC has not been well clarified. MATERIALS AND METHODS: In this experimental study, the UC model was induced in Wistar rats by administration of 2 ml 4% acetic acid into the large colon through the rectum. Animals were anesthetized after 48 h; their colon tissue samples were isolated for macroscopic and histopathological examination. The expression of receptor1-7 of CXC chemokine was assessed by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) technique. RESULTS: Heavy infiltration of neutrophils, coagulative necrosis, and ulcers were observed in H and E staining, which pathologically proved the UC model. qRT-PCR results indicated that CXCR2 as one of the important ELR+ chemokine family receptors bears the highest expression in the UC group (32 fold) than the control group (P ≤ 0.05). In addition, other CXCRs of this group including CXCR1 did not possess any change (P > 0.05). In contrast, RLR negative chemokine family receptors did not show any changes with the normal group. CONCLUSION: The results showed that CXCR2 is the only receptor for CXCL family which was remarkably upregulated in experimental UC and that CXCR2 might play a significant role in the pathogenesis of UC.

18.
J Inflamm Res ; 12: 167-174, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31417300

RESUMO

Background: The presence of neutrophil-rich inflammation in colon tissues of patients with ulcerative colitis (UC) is one of the most important histological characteristics of this disease. However, the expression of CXCL chemokines governing the infiltration of neutrophils in UC has not been well elucidated. Materials and methods: In this experimental study, the UC model was induced in Wistar rats by administration of 2 mL 4% acetic acid into the large colon through the rectum. Animals were anesthetized after 48 hrs; their colon tissue samples were isolated for macroscopic and histopathological examinations. The expression of CXCL family was assessed by reverse transcription polymerase chain reaction (qRT-PCR) technique. Results: Heavy infiltration of neutrophils, coagulation necrosis, and ulcers were observed in H&E staining, which pathologically proved the UC model. qRT-PCR results showed that ELR+ CXC chemokines such as CXCL6 and CXCL3 had the highest expression in the UC group, which was 49 and 28 times higher than that of the control group, respectively. In addition, other chemokines of this group including CXCL1, CXCL2, and CXCL7 had a significant increase compared to the control group (P≤0.05). However, ELR- CXC chemokines such as CXCL4, CXCL13, and CXCL16 showed a smaller upregulation, while CXCL14 chemokine showed a significant decrease compared to the control group (P≤0.05). However, the expression of CXCL9-12 and CXCL17 did not change. Conclusion: The results showed that the ELR+ CXC chemokines, especially CXCL6 and CXCL3, many involved in the pathogenesis of UC; therefore, CXCL6 and CXCL3 chemokines can be used as therapeutic targets for UC, although more studies using human samples are required.

19.
Basic Clin Neurosci ; 9(2): 147-156, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29967674

RESUMO

INTRODUCTION: This study aimed to investigate sleep architecture in patients with primary snoring and obstructive sleep apnea. METHODS: In this study, we analyzed polysomnographic data of 391 clients who referred to Sleep Disorders Research Center (SDRS). These people were classified into three groups based on their Apnea-Hypopnea Index (AHI) and snoring; control, Primary Snoring (PS), and Obstructive Sleep Apnea (OSA) group. Sleep architecture variables were then assessed in all groups. RESULTS: The results of this study indicated a decrease in deep sleep or Slow Waves Sleep (SWS) and increase in light sleep or stage 1 of non-REM sleep (N1) in OSA patients compared with the control and PS groups. After controlling the effects of confounding factors, i.e. age and Body Mass Index (BMI) (which was performed through multiple regression analysis) significant differences were observed among the three groups with regard to N1. However, with regard to SWS, after controlling confounding variables (age and BMI), no significant difference was found among the groups. CONCLUSION: The results indicated that OSA, regardless of age and BMI, may increase light (N1) sleep possibly via a decline in blood oxygen saturation (SpO2 ). Such increase in N1 may be responsible for brain arousal. In addition, by controlling confounding factors (age and BMI), OSA did not affect SWS in OSA patients. However, further research is necessary to determine sleep architecture in more detail in the patients with OSA.

20.
Acta Anaesthesiol Taiwan ; 54(2): 65-9, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27440278

RESUMO

OBJECTIVE: Tolerance to the analgesic effect is the main side effect of chronic administration of opioids. Several drugs have been studied to try to find agents to prevent the development of this phenomenon. In the present study we aimed to evaluate the effect of thalidomide on morphine-induced tolerance to the analgesic effect. METHODS: Groups of male rats were randomly rendered and received daily morphine in combination with thalidomide vehicle or thalidomide (2.5 mg/kg, 5 mg/kg, or 10 mg/kg, intraperitoneally). Nociception was measured using the plantar test apparatus. Latency time was recorded when the animal reacted to the light stimulus; licking or raising its hind paw. Treatments and evaluations continued until completion of tolerance to the analgesic effect of morphine. RESULTS: Our findings indicated that tolerance was achieved following 11 days of morphine administration, while thalidomide postponed the day of tolerance completion for 4 days (2.5 mg/kg and 5 mg/kg thalidomide) or 10 days (10 mg/kg thalidomide). Moreover, thalidomide prevented the morphine-induced shift to the right of the ED50 in the dose-response curve. CONCLUSION: It was concluded that thalidomide attenuated the morphine-induced tolerance to the analgesic effect.


Assuntos
Morfina/farmacologia , Talidomida/farmacologia , Animais , Relação Dose-Resposta a Droga , Tolerância a Medicamentos , Masculino , Ratos , Ratos Wistar
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