Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 6 de 6
Filter
Add more filters










Database
Language
Publication year range
1.
Arch Physiol Biochem ; 129(4): 933-942, 2023 Dec.
Article in English | MEDLINE | ID: mdl-33632048

ABSTRACT

This study declared effect of spexin (SPX) on renal dysfunction in obese rats and its potential mitigating mechanisms which could mediated via galanin receptor-2 (GALR-2). Thirty two 32 Wistar male rats were arranged into four groups: control, high fat/fructose diet (HFFD), HFFD + SPX and HFFD + M871 (galanin receptor 2 antagonist)+SPX. At the termination of the experiment, urine volume, body mass index, Lee index and mean arterial blood pressure were assessed. Renal function was evaluated. Lipid profile, fasting glucose, insulin, insulin resistance and SPX levels were estimated. Also, renal histopathological, immunohistochemical and relative gene expression of renal tissue were done. Also, renal protein carbonyl, reduced glutathione, interferon gamma, monocyte chemoattractant protein-1, interleukin-10 and hydroxyproline were determined.Our results explored that SPX treatment prominently mitigated the metabolic changes and renal dysfunction induced by HFFD via GALR-2. SPX improved insulin resistance, dyslipidemia, renal oxidative stress, inflammation, apoptosis, and fibrosis. So, SPX can be considered as prospective therapeutic agent for treating renal dysfunction.


Subject(s)
Insulin Resistance , Kidney Diseases , Animals , Male , Rats , Kidney Diseases/drug therapy , Kidney Diseases/etiology , Kidney Diseases/prevention & control , Obesity/metabolism , Rats, Wistar , Receptor, Galanin, Type 2 , Receptors, Galanin
2.
Br J Pharmacol ; 179(13): 3363-3381, 2022 07.
Article in English | MEDLINE | ID: mdl-35064582

ABSTRACT

BACKGROUND AND PURPOSE: Varicocele is a leading cause of male infertility. Melatonin is a highly pleiotropic neurohormone. We aimed to characterize the melatonin epigenetic potential in varicocele and the involved molecular mechanisms. EXPERIMENTAL APPROACH: Fifty-two male albino rats were randomly divided into four groups (13 rats each): control (I), melatonin (II), varicocele (III) and melatonin treated varicocele (IV) groups. Left varicocele was induced by partial left renal vein ligation. Reproductive hormones, epididymal sperm functional parameters, testicular 3/17 ß-hydroxysteroid dehydrogenases, antioxidant enzymes, malondialdehyde, nicotinamide adenine dinucleotide phosphate oxidase, 8-hydroxy-2'-deoxyguanosine and histopathological/Johnsen's score were evaluated. Flow cytometry and Comet were carried out to explore extent of sperm and testicular DNA damage. Testicular expression of silent information regulator 1 (SIRT1), forkhead transcription factors-class O (type1) (FOXO1), tumour suppressor gene, P53, cation channels of sperm (CatSper) and steroidogenic acute regulatory protein was evaluated by western blot technique. Testicular expression of Bcl-2 and its associated X protein and nuclear factor kappa-light-chain-enhancer of activated B cells were assayed by immunohistochemical staining. Testicular miR-34a expression was quantified by quantitative reverse transcription-polymerase chain reaction. KEY RESULTS: The varicocele induced testicular histological injury, enhanced oxidative stress, P53-mediated apoptosis, DNA damage and increased testicular miR-34a expression paralleled with down-regulated SIRT1/FOXO axis. Melatonin treatment of varicocele rats displayed antioxidant/anti-apoptotic efficacy and improved reproductive hormones axis, CatSper expression and fertility parameters. MiR-34a/SIRT1/FOXO1 epigenetic axis integrates testicular melatonin mediated intracellular transduction cascades in varicocele. CONCLUSION AND IMPLICATIONS: Melatonin can be used as an adjuvant therapy to improve varicocele and its complication.


Subject(s)
Melatonin , MicroRNAs , Sirtuin 1 , Varicocele , Animals , Antioxidants/metabolism , Antioxidants/pharmacology , Epigenesis, Genetic , Fertility , Male , Melatonin/pharmacology , MicroRNAs/metabolism , Oxidative Stress , Rats , Sirtuin 1/genetics , Sirtuin 1/metabolism , Tumor Suppressor Protein p53/metabolism , Varicocele/metabolism , Varicocele/pathology
3.
J Physiol Biochem ; 77(2): 305-320, 2021 May.
Article in English | MEDLINE | ID: mdl-33635523

ABSTRACT

Diabetic retinopathy (DR) is the most common diabetic neurovascular complication, and the leading cause of preventable blindness among working-age individuals. Recently, agmatine, the endogenous decarboxylated L-arginine, has gained attention as a pleiotropic agent that modulates the diabetes-associated decline in quality of life, and exhibited varied protective biological effects. Diabetes was induced by a single streptozotocin (STZ, 50 mg/kg, i.p.) injection. When diabetes was verified, the animals were randomly allocated into three groups (16 rat each); diabetic, agmatine-treated diabetic (1 mg/kg, daily, for 12 weeks), and control group. Blood glucose homeostasis, retinal redox status, apoptotic parameters, nitric oxide synthase (NOS), nitric oxide (NO), vascular endothelial growth factor (VEGF), glutamate, glutamine, glutamine synthase (GS) activity, nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB), and mitogen-activated protein kinase (MAPKs) pathways were assayed biochemically. Retinal vascular permeability was measured. Retinal morphology was evaluated by hematoxylin and eosin staining. Retinal N-methyl-D-aspartic acid receptor1 (NMDAR1) and glutamate aspartate transporter (GLAST) mRNA were quantified. Glucose transporter 1, pro-caspase3, and glial fibrillary acidic protein (GFAP) expression were quantified by immunohistochemistry. Chronic agmatine treatment abrogated STZ-induced retinal neurodegeneration features including gliosis, and neuronal apoptosis, restored retinal vascular permeability, mostly through antioxidant, anti-apoptotic capacity, abolishing glutamate excitotoxicity, modulating the activity of NMDARs, MAPKs/NFκB, and NOS/NO pathways. By restoring the molecular and functional background of retinal neurovascular homeostatic balance, agmatine would be appropriate therapeutic option acting upstream of the DR, impeding its progression.


Subject(s)
Agmatine/pharmacology , Antioxidants/pharmacology , Diabetes Mellitus, Experimental/drug therapy , Diabetic Retinopathy/drug therapy , Hypoglycemic Agents/pharmacology , Neuroprotective Agents/pharmacology , Retina/drug effects , Animals , Blood Glucose/metabolism , Caspase 3/genetics , Caspase 3/metabolism , Diabetes Mellitus, Experimental/chemically induced , Diabetes Mellitus, Experimental/genetics , Diabetes Mellitus, Experimental/pathology , Diabetic Retinopathy/chemically induced , Diabetic Retinopathy/genetics , Diabetic Retinopathy/pathology , Excitatory Amino Acid Transporter 1/genetics , Excitatory Amino Acid Transporter 1/metabolism , Gene Expression Regulation/drug effects , Glial Fibrillary Acidic Protein/genetics , Glial Fibrillary Acidic Protein/metabolism , Glucose Transporter Type 1/genetics , Glucose Transporter Type 1/metabolism , Glutamate-Ammonia Ligase/genetics , Glutamate-Ammonia Ligase/metabolism , Glutamic Acid/metabolism , Male , NF-kappa B/genetics , NF-kappa B/metabolism , Nitric Oxide/metabolism , Nitric Oxide Synthase Type I/genetics , Nitric Oxide Synthase Type I/metabolism , Oxidative Stress , Rats , Receptors, N-Methyl-D-Aspartate/genetics , Receptors, N-Methyl-D-Aspartate/metabolism , Retina/metabolism , Retina/pathology , Streptozocin/administration & dosage , Treatment Outcome , Vascular Endothelial Growth Factor A/genetics , Vascular Endothelial Growth Factor A/metabolism
4.
J Biochem Mol Toxicol ; 35(5): e22725, 2021 May.
Article in English | MEDLINE | ID: mdl-33491863

ABSTRACT

This study investigated the potential effect of adrenomedullin (ADM) on metabolic and endocrinal dysfunctions in experimentally induced polycystic ovary. Twenty-four female Wistar rats were allocated into three groups: control; polycystic ovary syndrome (PCOS) in which PCOS was induced by letrozole, orally in a dose of 1 mg/kg once daily for 3 weeks; and ADM group in which ADM was injected intraperitonally in a dose of 3.5/µg/twice daily for 4 weeks. At the end of the experimental period, the serum sex hormone profile, ADM, fasting glucose, insulin, homeostatic model assessment of insulin resistance, and lipid parameters were determined. Ovarian tissue homogenates were used to determine malondialdehyde, total antioxidant capacity, glutathione peroxidase activity, tumor necrosis factor α, interleukin 6, B cell lymphoma-2 (Bcl-2), and Bcl-2 associated X protein. The profibrotic growth factors, including transforming growth factor ß1 and connective tissue growth factor, were determined; and also, the relative gene expression of endoplasmic reticulum (ER) stress, including (Xbox-binding protein-1 [XBP-1], activating transcription factor 6 [ATF6], and homologous protein [CHOP]), serine/threonine kinase 1 (Akt1), phosphatidylinositol 3-kinase (PI3K), and peroxisome proliferator-activated receptor γ (PPAR-γ) were determined. Finally, histopathological analysis of the ovaries was evaluated. PCOS group exhibited increased ER stress, suppressing of PI3K/Akt1 and PPAR-γ pathways, imbalance of sex hormonal profile, hyperglycemia, insulin resistance, dyslipidemia, increased profibrotic factors, and abnormal ovarian histopathological picture, while ADM treatment alleviated these disturbances occurring in the PCOS model. We concluded that ADM mitigated PCOS via attenuating the ER stress, in addition to activation of PI3K/Akt1 and PPAR-γ pathways, its antioxidant, anti-inflammatory, antiapoptotic, and antifibrotic properties.


Subject(s)
Adrenomedullin/pharmacology , Endoplasmic Reticulum Stress/drug effects , Gene Expression Regulation/drug effects , Polycystic Ovary Syndrome/metabolism , Signal Transduction/drug effects , Animals , Disease Models, Animal , Female , Letrozole/toxicity , Polycystic Ovary Syndrome/chemically induced , Polycystic Ovary Syndrome/drug therapy , Rats , Rats, Wistar
5.
IUBMB Life ; 72(7): 1379-1392, 2020 07.
Article in English | MEDLINE | ID: mdl-32107872

ABSTRACT

This study purposed to examine the prospective curative role of lipoxin A4 (LXA4 ) in induced gastric ulcer in rats and explore the possible involvement of mitochondrial dynamics signaling pathway. Forty-eight male Wistar rats were divided into four groups: control, indomethacin (IND), IND + omeprazole (IND + Omez), and IND+ LXA4 groups. At the end of the experiment, the gastric pH, gastric fluid volume, total gastric acidity, ulcer index, and curative index were estimated. The gene expression of mitochondrial related protein 1 and mitofusin 2 were determined. In addition, some mitochondrial parameters include mitochondrial transmembrane potential, complex-I activity and reactive oxygen species were measured. Also, some gastric biochemical parameters, histopathological, and immunohistochemical analyses of the gastric mucosa were determined. We found that IND induced gastric ulcer, as manifested by the biochemical, histopathological, and immunohistochemical analyses. Both Omez and LXA4 treatment for 15 days alleviated the IND-induced gastric ulcer as explored by ameliorating the biochemical, histopathological, and immunohistochemical findings. We concluded that LXA4 mitigated the IND-induced gastric ulcer via improving the mitochondrial dynamic imbalance and mitochondrial dysfunction, in addition to its anti-apoptotic, anti-inflammatory, and antioxidant properties.


Subject(s)
Anti-Inflammatory Agents/administration & dosage , Indomethacin/toxicity , Lipoxins/administration & dosage , Mitochondria/drug effects , Mitochondrial Dynamics , Stomach Ulcer/drug therapy , Animals , Anti-Inflammatory Agents, Non-Steroidal/toxicity , Male , Prospective Studies , Rats , Rats, Wistar , Reactive Oxygen Species/metabolism , Signal Transduction , Stomach Ulcer/chemically induced , Stomach Ulcer/metabolism , Stomach Ulcer/pathology
6.
Arch Biochem Biophys ; 671: 123-129, 2019 08 15.
Article in English | MEDLINE | ID: mdl-31295432

ABSTRACT

This study was designed to explore the effect of angiotensin 1-7 (Ang 1-7) on experimentally induced-preeclampsia in Wistar rats targeting the role of peroxisome proliferator-activated receptors gamma expression (PPARs-γ) & asymmetric dimethylarginine (ADMA). 30 female Wistar rats were divided into three groups: Normal pregnant (NP), preeclampsia (PE), and preeclampsia treated with Ang 1-7 (PE + Ang 1-7) groups. Reduced uterine perfusion pressure (RUPP) model was induced on GD14. On GD18, protein in urine, urine volume and urinary sodium excretion were determined. On GD19, the systolic blood pressure (SBP) was measured, and the gene expression of PPARs-γ were determined. The serum samples were separated for determination of Ang 1-7, ADMA, soluble fms-like tyrosine kinase (sFlt-1), vascular endothelial growth factor (VEGF), nitric oxide (NO) products, endothelial nitric oxide synthase (eNOS) activity, interleukin-6 (IL-6), interleukin-10 (IL-10), malondialdehyde (MDA), and total anti-oxidant capacity (T-AOC). Compared to NP group, SBP, urine protein, serum levels of ADMA, sFlt-1, IL-6 and MDA significantly increased, while expression of PPARs-γ, serum levels of Ang 1-7, VEGF, NO products, eNOS, IL-10 and T-AOC significantly decreased in PE group, while treatment of Ang 1-7 significantly ameliorated all these studied parameters as compared to PE group. We concluded that Ang 1-7 attenuated the symptoms of preeclampsia, which might be via increasing the expression of PPARs-γ and reduction of ADMA levels which could explain its anti-hypertensive, anti-angiogenic, anti-inflammatory and antioxidant effects.


Subject(s)
Angiotensin I/therapeutic use , Arginine/analogs & derivatives , PPAR gamma/metabolism , Peptide Fragments/therapeutic use , Pre-Eclampsia/drug therapy , Animals , Arginine/metabolism , Blood Pressure/drug effects , Female , Oxidative Stress/drug effects , Placenta/metabolism , Pregnancy , Proteinuria/drug therapy , Rats, Wistar , Sodium/urine
SELECTION OF CITATIONS
SEARCH DETAIL
...