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1.
Bol. latinoam. Caribe plantas med. aromát ; 20(3): 303-314, may. 2021. tab, ilus
Article in English | LILACS | ID: biblio-1343478

ABSTRACT

In this study, against streptozotocin (STZ) induced diapetic nephropathy (DN); it is aimed to investigate the use of thymoquinone (TQ) and ß-aminoisobutyric acid (BAIBA) and to compare the effects of these agents. With random selection of 35 male rats, five groups (seven rats in each group) were constituted as follows: Control, STZ, STZ + TQ, STZ + BAIBA, STZ + TQ + BAIBA. In the STZ group; body weight, glutathione (GSH) and insulin levels decreased, relative kidney weight, malondialdehyde (MDA), glucose, blood urea nitrogen (BUN) and creatinine (Cr) levels were increased. Also, in kidney tissue; histopathological changes (such as thickening of the capsular, glomerular and tubular basement membranes, increased mesangial matrix amount, increased cytoplasmic vacuolization in some of the tubular epithelial cells, increased tumor necrosis factor-alpha (TNF-α) expression, and inflammatory cell infiltrations in interstitial tissue) were detected. It was observed that these changes occurring after diabetes mellitus (DM) reversed significantly in TQ, BAIBA and TQ + BAIBA groups.


En este estudio, contra la nefropatía diapética (ND) inducida por estreptozotocina (STZ); tiene como objetivo investigar el uso de timoquinona (TQ) y ácido ß-aminoisobutírico (BAIBA) y comparar los efectos de estos agentes. Con la selección aleatoria de 35 ratas macho, se constituyeron cinco grupos (siete ratas en cada grupo) como sigue: Control, STZ, STZ + TQ, STZ + BAIBA, STZ + TQ + BAIBA. En el grupo STZ; el peso corporal, los niveles de glutatión (GSH) y de insulina disminuyeron, el peso relativo de los riñones, el malondialdehído (MDA), la glucosa, el nitrógeno ureico en sangre (BUN) y los niveles de creatinina (Cr) aumentaron. Además, en tejido renal; se detectaron cambios histopatológicos (como engrosamiento de las membranas basales capsular, glomerular y tubular, aumento de la cantidad de matriz mesangial, aumento de la vacuolización citoplasmática en algunas de las células epiteliales tubulares, aumento de la expresión del factor de necrosis tumoral alfa (TNF-α) e infiltraciones de células inflamatorias en tejido intersticial). Se observó que estos cambios que ocurren después de la diabetes mellitus (DM) se revirtieron significativamente en los grupos TQ, BAIBA y TQ + BAIBA.


Subject(s)
Animals , Male , Rats , Benzoquinones/administration & dosage , Diabetic Nephropathies/drug therapy , Aminoisobutyric Acids/administration & dosage , Blood Urea Nitrogen , Body Weight , Immunohistochemistry , Rats, Sprague-Dawley , Streptozocin , Oxidative Stress , Creatinine/analysis , Disease Models, Animal , Glucose/analysis , Glutathione/analysis , Kidney/drug effects
2.
Braz. j. med. biol. res ; 54(11): e11352, 2021. tab, graf
Article in English | LILACS | ID: biblio-1339450

ABSTRACT

Diabetes mellitus is associated with neural and micro- and macrovascular complications. Therapeutic options for these complications are limited and the delivery of mesenchymal stem cells into lesions have been reported to improve the healing process. In this work, the effects of the administration of a lineage of human bone marrow mesenchymal stem cells immortalized by the expression of telomerase (hBMSC-TERT) as a potential therapeutic tool for wound healing in diabetic rats were investigated. This is the first description of the use of these cells in diabetic wounds. Dorsal cutaneous lesions were made in streptozotocin-induced diabetic rats and hBMSC-TERT were subcutaneously administered around the lesions. The healing process was evaluated macroscopically, histologically, and by birefringence analysis. Diabetic wounded rats infused with hBMSC-TERT (DM-TERT group) and the non-diabetic wounded rats not infused with hBMSC-TERT (CW group) had very similar patterns of fibroblastic response and collagen proliferation indicating improvement of wound healing. The result obtained by birefringence analysis was in accordance with that obtained by the histological analysis. The results indicated that local administration of hBMSC-TERT in diabetic wounds improved the wound healing process and may become a therapeutic option for wounds in individuals with diabetes.


Subject(s)
Humans , Animals , Rats , Telomerase , Diabetes Mellitus, Experimental , Mesenchymal Stem Cells , Wound Healing , Streptozocin
3.
Bol. latinoam. Caribe plantas med. aromát ; 20(2): 132-146, 2021. ilus, tab
Article in English | LILACS | ID: biblio-1342208

ABSTRACT

We investigated the effects of dichloromethane extract (DME) from Myrcia splendenson alterations caused by type 2 diabetes in the blood and kidney of rats, in order to reduce side effects caused by synthetic drugs. Rats received streptozotocin (60 mg/kg),15 minutes after nicotinamide (120 mg/kg) or water. After 72 hours, the glycemic levels were evaluated to confirm diabetes and the animals received (15 days) DME (25, 50, 100 or 150 mg/Kg) or water. DME partially reversed hyperglycemia and (100 and 150 mg/kg) reversed hypertriglyceridemia. Histopathological findings elucidated that DME reduced damage to pancreatic islets. DME 150 mg/kgreversed the increases in TBA-RS, the reduction in the sulfhydryl content, 100 and 150 mg/kg increased CAT, reversed the decrease in GSH-Px and increased it activity in the blood. DME 150 mg/kg reversed CAT and GSH-Px reductions in the kidney. We believe that DME effects might be dependent on the presence of phenolic compounds.


Investigamos los efectos del extracto de diclorometano (DME)de Myrcia splendens sobre las alteraciones causadas por la diabetes tipo 2 en la sangre y los riñones de las ratas, para reducir los efectos secundarios causados por las drogas sintéticas. Las ratas recibieron estreptozotocina (60 mg/kg), 15 minutos después de la nicotinamida (120 mg/kg) o agua. Después de 72 horas, se confirmo la diabetes y los animales recibieron (15 días) DME (25, 50, 100 o 150 mg/Kg) o agua. DME revierte parcialmente la hiperglucemia y revierte la hipertrigliceridemia. DME redujo el daño a los islotes pancreáticos. DME revirtió los aumentos en TBA-RS, la reducción en el contenido de sulfhidrilo, aumentó la CAT, revirtió la disminución en GSH-Px y aumentó su actividad en la sangre. Además, DME revirtió las reducciones de CAT y GSH-Px en el riñón. Creemos que los efectos provocados por DME pueden depender de la presencia de compuestos fenólicos.


Subject(s)
Animals , Male , Rats , Plant Extracts/administration & dosage , Myrtaceae/chemistry , Diabetes Mellitus, Experimental/drug therapy , Hypoglycemic Agents/administration & dosage , Methylene Chloride/administration & dosage , Blood Glucose/drug effects , Plant Extracts/chemistry , Chromatography, High Pressure Liquid , Rats, Wistar , Streptozocin , Oxidative Stress/drug effects , Spectrometry, Mass, Electrospray Ionization , Phenolic Compounds/analysis , Hypolipidemic Agents/administration & dosage , Antioxidants/administration & dosage
4.
Article in English | WPRIM | ID: wpr-880354

ABSTRACT

BACKGROUND@#Periploca aphylla is used by local population and indigenous medicine practitioners as stomachic, tonic, antitumor, antiulcer, and for treatment of inflammatory disorders. The aim of this study was to evaluate antidiabetic effect of the extract of P. aphylla and to investigate antioxidant and hypolipidemic activity in streptozotocin (STZ)-induced diabetic rats.@*METHODS@#The present research was conducted to evaluate the antihyperglycemic potential of methanol extract of P. aphylla (PAM) and subfractions n-hexane (PAH), chloroform (PAC), ethyl acetate (PAE), n-butanol (PAB), and aqueous (PAA) in glucose-overloaded hyperglycemic Sprague-Dawley rats. Based on the efficacy, PAB (200 mg/kg and 400 mg/kg) was tested for its antidiabetic activity in STZ-induced diabetic rats. Diabetes was induced via intraperitoneal injection of STZ (55 mg/kg) in rat. Blood glucose values were taken weekly. HPLC-DAD analysis of PAB was carried out for the presence of various polyphenols.@*RESULTS@#HPLC-DAD analysis of PAB recorded the presence of rutin, catechin, caffeic acid, and myricetin. Oral administration of PAB at doses of 200 and 400 mg/kg for 21 days significantly restored (P < 0.01) body weight (%) and relative liver and relative kidney weight of diabetic rats. Diabetic control rats showed significant elevation (P < 0.01) of AST, ALT, ALP, LDH, total cholesterol, triglycerides, LDL, creatinine, total bilirubin, and BUN while reduced (P < 0.01) level of glucose, total protein, albumin, insulin, and HDL in serum. Count of blood cells and hematological parameters were altered in diabetic rats. Further, glutathione peroxidase, catalase, superoxide dismutase, glutathione reductase, and total soluble protein concentration decreased while concentration of thiobarbituric acid reactive substances and percent DNA damages increased (P < 0.01) in liver and renal tissues of diabetic rats. Histopathological damage scores increased in liver and kidney tissues of diabetic rats. Intake of PAB (400 mg/kg) resulted in significant improvement (P < 0.01) of above parameters, and results were comparable to that of standard drug glibenclamide.@*CONCLUSION@#The result suggests the antihyperglycemic, antioxidant, and anti-inflammatory activities of PAB treatment in STZ-compelled diabetic rat. PAB might be used as new therapeutic agent in diabetic patients to manage diabetes and decrease the complications.


Subject(s)
1-Butanol/chemistry , Administration, Oral , Animals , Diabetes Mellitus, Experimental/drug therapy , Dose-Response Relationship, Drug , Hypoglycemic Agents/chemistry , Male , Periploca/chemistry , Phytochemicals/chemistry , Plant Extracts/chemistry , Rats , Rats, Sprague-Dawley , Streptozocin/adverse effects
5.
Braz. j. med. biol. res ; 53(7): e9628, 2020. tab, graf
Article in English | LILACS, ColecionaSUS | ID: biblio-1132530

ABSTRACT

Ophiopogonin D (OP-D) is the principal pharmacologically active ingredient from Ophiopogon japonicas, which has been demonstrated to have numerous pharmacological activities. However, its protective effect against renal damage in streptozotocin (STZ)-induced diabetic nephropathy (DN) rats remains unclear. The present study was performed to investigate the protective effect of OP-D in the STZ-induced DN rat model. DN rats showed renal dysfunction, as evidenced by decreased serum albumin and creatinine clearance, along with increases in serum creatinine, blood urea nitrogen, TGF-β1, and kidney hypertrophy, and these were reversed by OP-D. In addition, STZ induced oxidative damage and inflammatory response in diabetic kidney tissue. These abnormalities were reversed by OP-D treatment. The findings obtained in the present study indicated that OP-D might possess the potential to be a therapeutic agent against DN via inhibiting renal inflammation and oxidative stress.


Subject(s)
Animals , Male , Rats , Saponins/therapeutic use , Oxidative Stress/drug effects , Ophiopogon/chemistry , Diabetes Mellitus, Experimental/drug therapy , Diabetic Nephropathies/drug therapy , Inflammation/prevention & control , Spirostans/therapeutic use , Rats, Sprague-Dawley , Streptozocin
6.
Article in English | LILACS, BBO | ID: biblio-1135564

ABSTRACT

Abstract Objective: To investigate the differences of receptor activator of nuclear factor-κB ligand (RANKL) and Osteoprotegerin (OPG) expressions between normoglycemic and hyperglycemic Wistar rats (Rattus Novergicus) during Orthodontic Tooth Movement (OTM). Material and Methods: This study was true experimental with post-test group only. Thirty-two healthy male Wistar rats, weighted around 200-250 grams, 12-20 weeks old, were used as OTM animal study. They were divided into 2 groups (n=16), normoglycemic rats (normal blood glucose 80-120 mg/dl) and hyperglycemic rats (>250 mg/dl) induced by Streptozotocin with a dose of 30 mg in PBS injection intraperitoneally. A NiTi closed coil spring was mounted between maxillary first molar and incisors with the light force 10gf/mm2 in both groups to induce OTM. The studied animals were then terminated on days 1, 3, 6, and 9, respectively, and premaxilla was extracted. RANKL and OPG expression were examined utilizing immunohistochemistry (IHC) analysis. One-way ANOVA and Tukey HSD (p<0.05) were utilized to analyze the differences in the expression of RANKL and OPG between groups. Results: The hyperglycemic group on day 1, 9 rats showed a significant increase in the expression of RANKL, whereas OPG expression decreased significantly on days 1, 3, and 9. Conclusion: There was a significant increase of RANKL expression and a decrease of OPG expression in hyperglycemic rats as documented immunohistochemically.


Subject(s)
Animals , Rats , Tooth Movement Techniques , Rats, Wistar , Streptozocin , Diabetes Mellitus , RANK Ligand , Hyperglycemia , Immunohistochemistry , Epidemiology, Experimental , Analysis of Variance , Investigative Techniques , Osteoprotegerin , Molar
7.
Braz. J. Pharm. Sci. (Online) ; 56: e18772, 2020. tab, graf
Article in English | LILACS | ID: biblio-1285509

ABSTRACT

There is emerging evidence for a dysregulation of insulin signaling in the brains of patients with Alzheimer's disease (AD) with overlapping molecular features to Type 2 Diabetes Mellitus (T2DM). In addition, T2DM is a known risk factor of AD. The goal of this study was to investigate the neurogenic and neuroprotective potential of rosmarinic acid (RA) in a streptozotocin (STZ)-induced combined with high fat diet (HFD) mouse model of diabetes. Animals were divided into four experimental groups (control, diabetic, diabetic + RA, RA only). Behavioral analysis was performed to assess spatial learning and anxiety levels of animals, whereas quantitative real time PCR was carried out to assess the gene expression levels of neuronal markers of neurogenesis (Ki67, DCX and NeuN). A significant decrease in memory and spatial learning was observed in the diabetic mice, which was substantially improved by RA treatment. RA also increased the gene expression of NeuN, DCX and Ki67, which were dysregulated in the diabetic model. This study proposes RA as a potential therapeutic agent to mitigate neuronal dysfunction associated with T2DM by promoting adult hippocampal neurogenesis.


Subject(s)
Animals , Male , Mice , Diabetes Mellitus, Type 2/diagnosis , Alzheimer Disease/diagnosis , Risk Factors , Streptozocin/pharmacokinetics , Neurogenesis/genetics , Real-Time Polymerase Chain Reaction/methods
8.
Int. j. high dilution res ; 19(3): 2-17, 2020.
Article in English | LILACS, HomeoIndex | ID: biblio-1146520

ABSTRACT

IntroductionDiabetes Mellitusis an emerging endocrine and metabolic disorder which has affected millions of people globally. Homeopathic system of medicine uses ultra-molecular doses for treatment of Diabetes Mellitus. Homeopathic medicines are prepared from plant, mineral, sarcodes,nosodes and animal parts. Insulinum 6 CH, Pancreatinum 6CH and Uranium nitricum 6 CHareused in homeopathy for treatment of Diabetes Mellitus. However,no preclinical studies have been investigated for the anti-diabetic effect and its safety.MethodsHomeopathic medicines Insulinum 6CH, Pancreatinum 6CHandUranium nitricum6CH(1012)dilution factor were used to examine antihyperglycemic effects in streptozotocin induced diabetic rats. After 28 daysoftreatment,bodyweight, Hematology, Biochemistry (serum glucose, urea, creatinine, SGPT, SGOT, ALP, Triglyceride and HDL-cholesterol), Oral Glucose Tolerance Test, HbA1C with histopathologyof (Liver, Kidney, Pancreas) weremeasured.ResultsAfter Streptozotocin induction, the animals have shown significant increase in the fasting blood glucose level (p<0.01) as compared to normal control animals. Treatment with homeopathic medicine Insulinum 6CH, Pancreatinum 6CHandUranium nitricum6CHpotency showed significant decrease in levels of Glucose (p<0.05), OGTT, Total protein (P<0.001), ALP (P<0.05), Cholesterol (P<0.001), SGPT (P<0.001), SGOT (p<0.01), Urea, HbA1C as compared to diabetic animal.ConclusionsIn the present study homeopathic medicine Insulinum 6CH, Pancreatinum 6CH andUranium nitricum6CHpotency exhibitantihyperglycemic effects in streptozotocin induced diabetic rats.(AU)


Subject(s)
Insulinum/therapeutic use , Pancreatinum/therapeutic use , Sarcodes , Uranium/therapeutic use , Streptozocin , Diabetes Mellitus/therapy , Homeopathy , Hypoglycemic Agents
9.
Article in English | WPRIM | ID: wpr-811139

ABSTRACT

BACKGROUND: Epithelial-to-mesenchymal transition (EMT) is required for renal fibrosis, which is a characteristic of diabetic nephropathy (DN). Our previous study demonstrated that fibroblast growth factor 21 (FGF21) prevented DN associated with the suppressing renal connective tissue growth factor expression, a key marker of renal fibrosis. Therefore, the effects of FGF21 on renal fibrosis in a DN mouse model and the underlying mechanisms were investigated in this study.METHODS: Type 1 diabetes mellitus was induced in C57BL/6J mice by intraperitoneal injections of multiple low doses of streptozotocin. Then, diabetic and non-diabetic mice were treated with or without FGF21 in the presence of pifithrin-α (p53 inhibitor) or 10-[4′-(N,N-Diethylamino)butyl]-2-chlorophenoxazine hydrochloride (10-DEBC) hydrochloride (Akt inhibitor) for 4 months.RESULTS: DN was diagnosed by renal dysfunction, hypertrophy, tubulointerstitial lesions, and glomerulosclerosis associated with severe fibrosis, all of which were prevented by FGF21. FGF21 also suppressed the diabetes-induced renal EMT in DN mice by negatively regulating transforming growth factor beta (TGF-β)-induced nuclear translocation of Smad2/3, which is required for the transcription of multiple fibrotic genes. The mechanistic studies showed that FGF21 attenuated nuclear translocation of Smad2/3 by inhibiting renal activity of its conjugated protein p53, which carries Smad2/3 into the nucleus. Moreover pifithrin-α inhibited the FGF21-induced preventive effects on the renal EMT and subsequent renal fibrosis in DN mice. In addition, 10-DEBC also blocked FGF21-induced inhibition of renal p53 activity by phosphorylation of mouse double minute-2 homolog (MDM2).CONCLUSION: FGF21 prevents renal fibrosis via negative regulation of the TGF-β/Smad2/3-mediated EMT process by activation of the Akt/MDM2/p53 signaling pathway.


Subject(s)
Animals , Connective Tissue Growth Factor , Diabetes Mellitus, Type 1 , Diabetic Nephropathies , Epithelial-Mesenchymal Transition , Fibroblast Growth Factors , Fibroblasts , Fibrosis , Hypertrophy , Injections, Intraperitoneal , Kidney , Mice , Phosphorylation , Streptozocin , Transforming Growth Factor beta , Tumor Suppressor Protein p53
10.
Article in English | WPRIM | ID: wpr-811138

ABSTRACT

BACKGROUND: Recent studies have shown that microRNAs (miRNAs) are involved in the process of cardiomyocyte apoptosis. We have previously reported that granulocyte-colony stimulating factor (G-CSF) ameliorated diastolic dysfunction and attenuated cardiomyocyte apoptosis in a rat model of diabetic cardiomyopathy. In this study, we hypothesized a regulatory role of cardiac miRNAs in the mechanism of the anti-apoptotic effect of G-CSF in a diabetic cardiomyopathy rat model.METHODS: Rats were given a high-fat diet and low-dose streptozotocin injection and then randomly allocated to receive treatment with either G-CSF or saline. H9c2 rat cardiomyocytes were cultured under a high glucose (HG) condition to induce diabetic cardiomyopathy in vitro. We examined the extent of apoptosis, miRNA expression, and miRNA target genes in the myocardium and H9c2 cells.RESULTS: G-CSF treatment significantly decreased apoptosis and reduced miR-34a expression in diabetic myocardium and H9c2 cells under the HG condition. G-CSF treatment also significantly increased B-cell lymphoma 2 (Bcl-2) protein expression as a target for miR-34a. In addition, transfection with an miR-34a mimic significantly increased apoptosis and decreased Bcl-2 luciferase activity in H9c2 cells.CONCLUSION: Our results indicate that G-CSF might have an anti-apoptotic effect through down-regulation of miR-34a in a diabetic cardiomyopathy rat model.


Subject(s)
Animals , Apoptosis , Diabetic Cardiomyopathies , Diet, High-Fat , Down-Regulation , Glucose , Granulocyte Colony-Stimulating Factor , In Vitro Techniques , Luciferases , Lymphoma, B-Cell , MicroRNAs , Models, Animal , Myocardium , Myocytes, Cardiac , Rats , Streptozocin , Transfection
11.
Acta cir. bras ; 34(11): e201901106, Nov. 2019. tab, graf
Article in English | LILACS | ID: biblio-1054683

ABSTRACT

Abstract Purpose: To investigate whether GDF11 ameliorates myocardial ischemia reperfusion (MIR) injury in diabetic rats and explore the underlying mechanisms. Methods: Diabetic and non-diabetic rats subjected to MIR (30 min of coronary artery occlusion followed by 120 min of reperfusion) with/without GDF11 pretreatment. Cardiac function, myocardial infarct size, creatine kinase-MB (CK-MB), lactate dehydrogenase (LDH), superoxide dismutase (SOD) 15-F2tisoprostane, autophagosome, LC3II/I ratio and Belcin-1 level were determined to reflect myocardial injury, oxidative stress and autophagy, respectively. In in vitro study, H9c2 cells cultured in high glucose (HG, 30mM) suffered hypoxia reoxygenation (HR) with/without GDF11, hydrogen peroxide (H2O2) and autophagy inhibitor 3-methyladenine (3-MA) treatment, cell injury; oxidative stress and autophagy were assessed. Results: Pretreatment with GDF11 significantly improved cardiac morphology and function in diabetes, concomitant with decreased arrhythmia severity, infarct size, CK-MB, LDH and 15-F2tisoprostane release, increased SOD activity and autophagy level. In addition, GDF11 notably reduced HR injury in H9c2 cells with HG exposure, accompanied by oxidative stress reduction and autophagy up-regulation. However, those effects were completely reversed by H2O2 and 3-MA. Conclusion: GDF11 can provide protection against MIR injury in diabetic rats, and is implicated in antioxidant stress and autophagy up-regulation.


Subject(s)
Animals , Male , Autophagy/drug effects , Myocardial Reperfusion Injury/metabolism , Myocardial Reperfusion Injury/drug therapy , Oxidative Stress/drug effects , Diabetes Mellitus, Type 1/metabolism , Growth Differentiation Factors/pharmacology , Reference Values , Superoxide Dismutase/analysis , Cardiotonic Agents/pharmacology , Myocardial Reperfusion Injury/pathology , Up-Regulation/drug effects , Cell Line , Blotting, Western , Reproducibility of Results , Rats, Sprague-Dawley , Streptozocin , Microscopy, Electron, Transmission , Diabetes Mellitus, Experimental/metabolism , Hemodynamics/drug effects , Antioxidants/pharmacology
12.
J. bras. nefrol ; 41(3): 315-322, July-Sept. 2019. tab, graf
Article in English | LILACS | ID: biblio-1040245

ABSTRACT

Abstract Introduction: It is hypothesized that increased macrophage migration inhibitory factor (MIF) expression may contribute to diabetic nephropathy (DN) pathogenesis. The aim of the present study was to investigate the renal effects of MIF inhibition in a diabetic experimental model. Methods: Eighteen male Wistar rats (230 ± 20 g) were divided into three groups: 1) control, 2) diabetic (STZ, 50 mg/kg, dissolved in saline, ip), 3) diabetic + MIF antagonist (p425, 1 mg/kg per day, ip, on the 21th day, for 21 consecutive days). The treatment started since we founwd a significant increase in urine albumin excretion (UAE) rate in the diabetic rats in comparison with the control rats. The rats were kept individually in metabolic cages (8 AM-2 PM) and urine samples were collected in the 21 and 42th day. At the end, blood and tissue samples were collected for biochemical (BS, UPE, urine GAG, BUN, Cr, Na, and K) and histological analyses. Results: The results of this study showed that MIF antagonist (p425) significantly decreased urine protein and GAG excretion, urine protein/creatinine ratio, and serum BUN and Cr in the streptozotocin-induced DN in the rats. Pathological changes were significantly alleviated in the MIF antagonist (p425)-administered DN rats. Conclusion: Collectively, these data suggested that MIF antagonist (p425) was able to protect against functional and histopathological injury in the DN.


Resumo Introdução: Supõe-se que elevações da expressão do fator de inibição da migração de macrófagos (MIF) possam contribuir para a patogênese da nefropatia diabética (ND). O objetivo do presente estudo foi investigar os efeitos renais da inibição do MIF em um modelo experimental diabético. Métodos: Dezoito ratos Wistar machos (230 ± 20g) foram divididos em três grupos: 1) controle, 2) diabético (STZ 50 mg/kg dissolvida em soro fisiológico, IP), 3) diabético + antagonista do MIF (p425 1 mg/kg por dia IP no 21o dia por 21 dias consecutivos). O tratamento começou após a identificação de aumento significativo na albuminúria nos ratos diabéticos em relação aos controles. Os ratos foram mantidos individualmente em gaiolas metabólicas (8h-14h) e amostras de urina foram colhidas no 21o e no 42o dia. Ao final do estudo, amostras de sangue e tecido foram colhidas para análises bioquímicas (BS, excreção urinária de proteína, excreção urinária de GAGs, BUN, Cr, Na e K) e histológicas. Resultados: O presente estudo demonstrou que o antagonista do MIF (p425) diminuiu significativamente proteinúria, excreção urinária de GAGs , relação proteína/creatinina na urina, BUN e Cr no grupo com ND induzida por estreptozotocina. As alterações patológicas foram significativamente abrandadas nos ratos com ND que receberam antagonista do MIF (p425). Conclusão: Coletivamente, os dados sugerem que o antagonista do MIF (p425) teve efeito protetor contra lesões funcionais e histopatológicas da ND.


Subject(s)
Animals , Male , Rats , Macrophage Migration-Inhibitory Factors/antagonists & inhibitors , Intramolecular Oxidoreductases/antagonists & inhibitors , Protective Agents/therapeutic use , Protective Agents/pharmacology , Diabetes Mellitus, Experimental/pathology , Diabetic Nephropathies/therapy , Blood Glucose , Rats, Wistar , Streptozocin/pharmacology , Creatinine/urine , Creatinine/blood , Diabetes Mellitus, Experimental/chemically induced , Diabetes Mellitus, Experimental/urine , Diabetes Mellitus, Experimental/blood , Diabetic Nephropathies/urine , Diabetic Nephropathies/pathology , Diabetic Nephropathies/blood , Albuminuria/drug therapy , Disease Models, Animal , Glycosaminoglycans/urine , Kidney/pathology , Macrophage Activation
13.
Article in Chinese | WPRIM | ID: wpr-772078

ABSTRACT

OBJECTIVE@#To investigate the effects of exendin-4 on hepatic lipid metabolism, fibrosis and oxidative stress in mice with streptozotocin (STZ)-induced diabetes and explore the underlying mechanisms.@*METHODS@#C57BL/6J mice were fed with high-fat diet (HFD) for 4 weeks and received intraperitoneal injections of 120 mg/kg STZ to induce diabetes. After successful modeling, the mice were randomized into diabetic control group and exendin-4 treatment group (DM+E4), and in the latter group, the mice were given a daily dose of 1 nmol/kg of exendin-4 for 8 weeks. The changes in the body weight (BW) and random blood glucose (RBG) in the mice were recorded. The mRNA expressions of the genes related with liver lipid metabolism, fibrosis and oxidative stress were analyzed using RT-PCR, and the structural changes of the liver tissues were observed with HE, Sirius red and oil red O staining; the expressions of TGF-β1, Nrf2 and HO-1 proteins in the liver tissues were detected using Western blotting.@*RESULTS@#The diabetic mice showed significantly higher RBG levels and BW with obvious lipid deposition, fibrosis and oxidative stress in the liver as compared with the normal control mice ( < 0.001). Exendin-4 treatment of the diabetic mice did not significantly lessened liver lipid deposition but obviously reduced the levels of RBG and TG ( < 0.05), lowered the expression levels of liver fibrosis-related genes TGF-β, -SMA and Col-Ⅰ ( < 0.05), increased the expression levels of the antioxidant genes Nrf2, HO-1 and GPX4 ( < 0.01), and enhanced the protein expressions of Nrf2 and HO-1 in the liver tissues ( < 0.01).@*CONCLUSIONS@#Exendin-4 improves liver fibrosis and oxidative stress in diabetic mice by activating Nrf2/HO-1 pathway without significantly reducing liver lipid deposition.


Subject(s)
Animals , Diabetes Mellitus, Experimental , Exenatide , Liver , Liver Cirrhosis , Mice , Mice, Inbred C57BL , NF-E2-Related Factor 2 , Oxidative Stress , Streptozocin
15.
Article in Chinese | WPRIM | ID: wpr-781658

ABSTRACT

To investigate the role of thioredoxin interacting protein(TXNIP)/ nucleotides-binding oligomerization domain-like receptor protein(NLRP)3 inflammasome in the sciatic nerve of streptozotocin(STZ)-induced diabetic rats. The diabetic rat model was established by single intraperitoneal injection of STZ.The rats with matched sex and age were taken as normal control group.The blood glucose and body weight were monitored.The mechanical withdrawal threshold was measured by von Frey filaments at 12 weeks after the model was established.At 12 weeks,the rats were sacrificed and the sciatic nerves were separated for Luxol fast blue staining,the expressions of TXNIP,NLRP3,caspase-1,and interleukin(IL)-1β were detected by immunohistochemistry and Western blot method,and the levels of IL-1β and IL-18 in serum were measured by enzyme-linked immunosorbent assay(ELISA). The expression of TXNIP protein in the sciatic nerve of diabetic rats was 3.78±0.08,which significantly increased than that in the normal control group(0.99±0.06)(=26.980,<0.0001).Compared with the normal control group(0.97±0.05),the expression of NLRP3 protein in the diabetic group(2.44±0.16)was significantly higher(=8.885,<0.0001).The expression of cleaved caspase-1 was 4.45±0.19 in the diabetic group and 1.08±0.06 in the normal control group,and the difference was significant(=16.900,<0.0001).The expression of IL-1β protein in the diabetic group(4.50±0.16)was significantly higher than that(1.19±0.08)in the normal control group(=18.630,<0.0001).Compared with the normal control group,the levels of IL-1β [(110.50±8.80)pg/ml (17.97±3.18)pg/ml,=9.892,<0.0001] and IL-18 [(591.70±8.78)pg/ml (160.70±8.33)pg/ml,=35.620,<0.0001] in the serum of diabetic rats significantly increased. The pathogenesis of diabetic peripheral neuropathy may be related to increased expression of TXNIP,activation of NLRP3 inflammasome,and downstream inflammation,which may provide a new target for diabetic peripheral neuropathy therapy.


Subject(s)
Animals , Diabetes Mellitus, Experimental , Inflammasomes , Nucleotides , Rats , Sciatic Nerve , Streptozocin , Thioredoxins
16.
Article in Chinese | WPRIM | ID: wpr-776545

ABSTRACT

OBJECTIVE@#To investigate the therapeutic effects of the black buckwheat leaf (BBL) in type 2 diabetes mellitus mice and its effects on pancreas and spleen.@*METHODS@#Forty male C57 / B16 mice (SPF) were randomly divided into normal control (NC) group (n=10) and the experimental group (n=30), the experimental group were fed with high sugar and high fat, combined with intraperitoneal injection of streptozotocin in small dose to establish the model of type 2 diabetes mellitus (T2DM). Those thirty model mice were randomly divided into 3 groups (n=10), diabetes mellitus group (DM), low dose of BBL (DM+L) treated group, high dose of BBL (DM+H) treated group. The mice in the NC group and the DM group were given normal saline per day, and the DM+L group and DM+H group were treated with black tartary buckwheat at the doses of 0.21g/kg·d and 0.42g/kg·d respectively. After 14 days. All mice were executed by cervical dislocation, then blood samples were collected, pancreas and spleen were removed for subsequent experiments. The serum levels of fasting blood glucose (FBG), triglyceride (TG), total cholesterol (TCH) and insulin were detected. TNF-α protein in spleen tissue was detected by ELISA kit. The morphology of pancreas tissue was observed by HE staining, and the spleen coefficient was calculated. The expression levels of insulin receptor substrate-1(IRS-1) mRNA and IRS-1 protein in pancreatic tissue were detected.@*RESULTS@#Compared with the control group, the serum levels of FBG, TC and TCH in the model group were increased significantly, while the serum level of insulin was decreased significantly (P<0.05), the expression of TNF-α protein in spleen tissues was obviously raised, the expressions of IRS-1 mRNA and IRS-1 protein in pancreatic tissue in model group were decreased significantly (P<0.05). Compared with the model group, the serum levels of FBG, TC and TCH were decreased significantly in the BBL treated groups. The serum insulin level, spleen coefficient, TNF-α protein expression level in spleen tissue, IRS-1 mRNA expression and IRS-1 protein expression levels in pancreatic tissue in BBL treated group were increased significantly (P< 0.05). High-dose black tartary buckwheat leaves (0.42g/kg·d) exerted a more significant effect.@*CONCLUSION@#Stem and leaf of black bitter buckwheat has significant therapeutic effects on reducing blood sugar and blood fat in type 2 diabetic mice, and has certain protective effects on pancreas and spleen of diabetic mice.


Subject(s)
Animals , Diabetes Mellitus, Experimental , Drug Therapy , Diabetes Mellitus, Type 2 , Drug Therapy , Fagopyrum , Chemistry , Male , Mice , Mice, Inbred C57BL , Pancreas , Plant Leaves , Chemistry , Plant Stems , Chemistry , Random Allocation , Spleen , Streptozocin
17.
Article in Chinese | WPRIM | ID: wpr-776542

ABSTRACT

OBJECTIVE@#To analyze the changes of blood biochemical index and the pathological changes of myocardium and kidney in type 2 diabetic mouse at different time points, which can provide the basis for the selection of type 2 diabetic modeling time for later research.@*METHODS@#After 6 weeks of feeding with high-fat diet, 24 healthy male ICR mice were injected with streptozocin (STZ, 30 mg/kg) intraperitoneally for 5 days to establish diabetic models. After 9 days, a random blood glucose ≥ 11.1 mmol / L was measured as diabetic mice. 4, 6 and 8 weeks after successfully preparing the diabetic mouse, 8 diabetic mice (a group)would be sacrificed each time. Then the biochemical and pathological conditions were analyzed: ① the indexes of heart and kidney were calculated. ②the serum levels of creatine kinase (CK), lactate dehydrogenase (LDH), creatinine (Cr) and blood urine nitrogen (BUN) were determined. ③ Histopathological changes of myocardium and renal tissues were observed by hematoxylin and eosin (HE) staining. Masson staining was used to observe the fibrosis of myocardium. PAS staining was adopted to observe the pathological changes of renal tissue. In addition, 8 ICR male mice were taken as the control group.@*RESULTS@#At the 4, 6 and 8 week, cardiac organ coefficient, the values of LDH and CK were all increased compared with the control group. Cardiomyocyte hypertrophy and myocardial fibrosis could be observed. Renal organ coefficient, the values of Cr and BUN were increased. Glomerular hypertrophy, basement membrane thickening and atrophy could be perceived.@*CONCLUSION@#At the 6 week, related biochemical and pathological changes in diabetic mice were comparatively obvious and breeding time was relatively short. Thus, 6 weeks after the preparation of the diabetic mice would be the optimal time for type 2 diabetes mellitus modeling, proper for inventions of drugs and other research purposes including pathology, physiology, biochemistry, etc.


Subject(s)
Animals , Diabetes Mellitus, Experimental , Pathology , Diabetes Mellitus, Type 2 , Pathology , Disease Models, Animal , Kidney , Pathology , Male , Mice , Mice, Inbred ICR , Streptozocin
18.
Article in Chinese | WPRIM | ID: wpr-776498

ABSTRACT

OBJECTIVE@#To investigate the therapeutic effects of puerarin on rats with type 2 diabetes mellitus (T2DM).@*METHODS@#T2DM models were established by high fat and high glucose feeding combined with a one-time intraperitoneal injection of streptozotocin (STZ, 60 mg/kg). Then the rats were randomly divided into normal group, model group, metformin group (MET, 40 mg/kg), puerarin low-dose group, medium-dose group and high-dose group (40, 80, 160 mg/kg), n=10. After the model was successfully established, rats were treated with corresponding drug intervention by intragastrical administration for 4 weeks. The body weight and fasting blood glucose (FBG) were measured per week, and blood samples were collected 24 h after the last administration, and serum levels of blood glucose, serum triglyceride (TG), total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-C), high-density lipoprotein-cholestrol (HDL-C), serum enzyme activities of aspartate aminotransferase (AST), alanine aminotransferase (ALT), blood urea nitrogen (BUN), serum creatinine (SCr), and blood uric acid (UA) were measured.@*RESULTS@#As compared with normal group, the body weight was decreased after 4 weeks-intervention in the model group, and the levels of FBG, TC, TG, LDL-C, ALT, AST, BUN, SCr and UA were all increased,while HDL-C level was decreased (P<0.05). As compared with model group,the body weight was increased after 4 weeks-intervention in metformin group and puerarin groups, and the levels of FBG, TC, TG, LDL-C, ALT, AST, BUN, SCr and UA were decreased (P<0.01); meanwhile, HDL-C level was increased significantly (P<0.05).@*CONCLUSION@#Puerarin can reduce the weight loss of T2DM rats, decrease the blood lipid and blood glucose levels of T2DM rats, which can be used to control T2DM.


Subject(s)
Animals , Blood Glucose , Diabetes Mellitus, Experimental , Drug Therapy , Diabetes Mellitus, Type 2 , Drug Therapy , Isoflavones , Pharmacology , Lipids , Blood , Random Allocation , Rats , Streptozocin , Weight Loss
19.
Article in English | WPRIM | ID: wpr-739800

ABSTRACT

BACKGROUND: This study investigated the role of NR2B in a modulated pain process in the painful diabetic neuropathy (PDN) rat using various pain stimuli. METHODS: Thirty-two Sprague-Dawley male rats were randomly allocated into four groups (n=8): control, diabetes mellitus (DM) rats and diabetic rats treated with ifenprodil at a lower dose (0.5 µg/day) (I 0.5) or higher dose (1.0 µg/day) (I 1.0). DM was induced by a single injection of streptozotocin at 60 mg/kg on day 0 of experimentation. Diabetic status was assessed on day 3 of the experimentation. The responses on both tactile and thermal stimuli were assessed on day 0 (baseline), day 14 (pre-intervention), and day 22 (post-intervention). Ifenprodil was given intrathecally for 7 days from day 15 until day 21. On day 23, 5% formalin was injected into the rats' hind paw and the nociceptive responses were recorded for 1 hour. The rats were sacrificed 72 hours post-formalin injection and an analysis of the spinal NR2B expression was performed. RESULTS: DM rats showed a significant reduction in pain threshold in response to the tactile and thermal stimuli and higher nociceptive response during the formalin test accompanied by the higher expression of phosphorylated spinal NR2B in both sides of the spinal cord. Ifenprodil treatment for both doses showed anti-allodynic and anti-nociceptive effects with lower expression of phosphorylated and total spinal NR2B. CONCLUSION: We suggest that the pain process in the streptozotocin-induced diabetic rat that has been modulated is associated with the higher phosphorylation of the spinal NR2B expression in the development of PDN, which is similar to other models of neuropathic rats.


Subject(s)
Animals , Diabetes Mellitus , Diabetic Neuropathies , Formaldehyde , Humans , Hyperalgesia , Male , N-Methylaspartate , Pain Measurement , Pain Threshold , Phosphorylation , Rats , Rats, Sprague-Dawley , Receptors, N-Methyl-D-Aspartate , Spinal Cord , Streptozocin
20.
Yonsei Medical Journal ; : 667-678, 2019.
Article in English | WPRIM | ID: wpr-762093

ABSTRACT

PURPOSE: The aim of this study was to investigate how type I diabetes mellitus (T1D) affects the folliculogenesis and oocyte development, fertilization, and embryo development. MATERIALS AND METHODS: A comparative animal study was conducted using two different mouse models of T1D, a genetic AKITA model and a streptozotocin-induced diabetes model. Ovarian function was assessed by gross observation, immunoblot, immunohistochemistry, oocyte counting, and ELISA for serum hormones (insulin, anti-Mullerian hormone, estradiol, testosterone, and progesterone). Maturation and developmental competence of metaphase II oocytes from control and T1D animals was evaluated by immunofluorescent and immunohistochemical detection of biomarkers and in vitro fertilization. RESULTS: Animals from both T1D models showed increased blood glucose levels, while only streptozotocin (STZ)-injected mice showed reduced body weight. Folliculogenesis, oogenesis, and preimplantation embryogenesis were impaired in both T1D mouse models. Interestingly, exogenous streptozotocin injection to induce T1D led to marked decreases in ovary size, expression of luteinizing hormone/chorionic gonadotropin receptor in the ovaries, the number of corpora lutea per ovary, oocyte maturation, and serum progesterone levels. Both T1D models exhibited significantly reduced pre-implantation embryo quality compared with controls. There was no significant difference in embryo quality between STZ-injected and AKITA diabetic mice. CONCLUSION: These results suggest that T1D affects folliculogenesis, oogenesis, and embryo development in mice. However, the physiological mechanisms underlying the observed reproductive effects of diabetes need to be further investigated.


Subject(s)
Animals , Anti-Mullerian Hormone , Biomarkers , Blood Glucose , Body Weight , Corpus Luteum , Diabetes Mellitus , Diabetes Mellitus, Type 1 , Embryonic Development , Embryonic Structures , Enzyme-Linked Immunosorbent Assay , Estradiol , Female , Female , Fertility , Fertilization , Fertilization in Vitro , Gonadotropins , Humans , Immunohistochemistry , Lutein , Mental Competency , Metaphase , Mice , Oocytes , Oogenesis , Ovary , Pregnancy , Progesterone , Reproduction , Streptozocin , Testosterone
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