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1.
J Ethnopharmacol ; 336: 118742, 2025 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-39197806

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: In traditional Persian medicine (TPM), people often use herbal infusions as a dosage form to treat diseases related to hyperglycemia, known as 'dam-kardeh'. Traditionally, herbal preparations of Eryngium bungei Boiss. (E. b), Tragopogon buphthalmoides (DC.) Boiss. (T. b), Salvia hydrangea DC. ex Benth. (S. h), and Juniperus polycarpos K. Koch. (J. p) are used to manage diabetes in Iran. However, there is no evidence of their effectiveness in controlling glucose levels and their mechanisms remain unclear. AIM OF THE STUDY: This study aimed to investigate whether traditional doses of plant infusions can have hypoglycemic and/or anti-hyperglycemic effects during fasting and/or postprandial states and establish the basis for future research on their potential mechanisms of action. MATERIALS AND METHODS: The effects of traditional doses of herbal extracts on blood glucose levels in STZ-NA-induced hyperglycemic rats were investigated in 2-h acute tests during fasting and postprandial states (with a glucose load). In addition, the potential inhibitory effect in vitro of enzymes involved in relevant pathways, such as gluconeogenesis (fructose-1,6-bisphosphatase, FBPase and glucose-6-phosphatase, G6Pase), carbohydrate breakdown (intestinal α-glucosidases), and insulin sensitivity (protein tyrosine phosphatase 1B, PTP-1B) was evaluated. Acute toxicity tests were carried out and HPLC-SQ-TOF was used to analyze the chemical profiles of the plant extracts. RESULTS: In the fasting state, T. b, S. h, and E. b were as effective as glibenclamide in lowering blood glucose levels in hyperglycemic rats. Moreover, all three suppressed G6Pase and FBPase enzymatic activity by 90-97% and 80-91%, respectively. On the other hand, significant postprandial hypoglycemic efficacy was observed for E. b, S. h, and T. b. Based on the AUC values, T. b caused a reduction comparable to the therapeutic efficacy of repaglinide. When investigating the possible mechanisms of action involved in this activity, E. b, S. h, and T. b showed significant inhibition of PTP-1B in vitro (>70%). Finally, all plant extracts showed no signs of acute toxicity. Several compounds that may contribute to biological activities were identified, including phenolic acids and flavonoid glycosides. CONCLUSIONS: The present study supports the traditional use of T. b, E. b and S. h for the control of diabetes in the fasting and postprandial state. Moreover, these plants were found to be rich in bioactive compounds with hypoglycemic and antihyperglycemic activities. On the other hand, J. p, showed a modest effect only in the fasting state and after 90 min. Further studies are needed to expand these results by analyzing the chemical composition and using complementary experimental models.


Assuntos
Glicemia , Diabetes Mellitus Experimental , Jejum , Hipoglicemiantes , Extratos Vegetais , Período Pós-Prandial , Animais , Hipoglicemiantes/farmacologia , Extratos Vegetais/farmacologia , Extratos Vegetais/administração & dosagem , Extratos Vegetais/química , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/sangue , Masculino , Irã (Geográfico) , Ratos , Medicina Persa , Ratos Wistar , Hiperglicemia/tratamento farmacológico , Plantas Medicinais/química , Estreptozocina , Juniperus/química
2.
Acta Cir Bras ; 39: e396124, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39356932

RESUMO

PURPOSE: To examine whether isoflurane preconditioning (IsoP) has a protective effect against renal ischemia/reperfusion injury (I/RI) in diabetic conditions and to further clarify the underlying mechanisms. METHODS: Control and streptozotocin-induced diabetic rats were randomly assigned to five groups, as follows: normal sham, normal I/R, diabetic sham, diabetic I/R, and diabetic I/R + isoflurane. Renal I/RI was induced by clamping renal pedicle for 45 min followed by reperfusion for 24 h. IsoP was achieved by exposing the rats to 2% isoflurane for 30 min before vascular occlusion. Kidneys and blood were collected after reperfusion for further analysis. Renal histology, blood urea nitrogen, serum creatinine, oxidative stress, inflammatory cytokines, and renal cell apoptosis were assessed. Furthermore, the expression of brahma related gene 1 (Brg1), nuclear factor-erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), and nuclear factor-κB (NF-κB) were determined. RESULTS: Compared with control, diabetic rats undergoing I/R presented more severe renal injury, oxidative stress, inflammatory reaction, and apoptosis with the impairment of Brg1/Nrf2/HO-1 signaling. All these alterations were significantly attenuated by pretreatment with isoflurane. CONCLUSIONS: These findings suggest that isoflurane could alleviate renal I/RI in diabetes, possibly through improving Brg1/Nrf2/HO-1 signaling.


Assuntos
Apoptose , Diabetes Mellitus Experimental , Precondicionamento Isquêmico , Isoflurano , Traumatismo por Reperfusão , Transdução de Sinais , Fatores de Transcrição , Animais , Masculino , Ratos , Anestésicos Inalatórios/farmacologia , Apoptose/efeitos dos fármacos , Diabetes Mellitus Experimental/complicações , DNA Helicases/metabolismo , Heme Oxigenase-1/metabolismo , Precondicionamento Isquêmico/métodos , Isoflurano/farmacologia , Rim/efeitos dos fármacos , Rim/irrigação sanguínea , Rim/patologia , Fator 2 Relacionado a NF-E2/metabolismo , NF-kappa B/metabolismo , Proteínas Nucleares/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Distribuição Aleatória , Ratos Sprague-Dawley , Traumatismo por Reperfusão/prevenção & controle , Transdução de Sinais/efeitos dos fármacos
3.
Cells ; 13(19)2024 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-39404390

RESUMO

Diabetes mellitus is associated with changes in intestinal morphology and the enteric nervous system. We previously reported constipation in Goto-Kakizaki (GK) rats, a non-obese model for type 2 diabetes mellitus. AIM: The morpho-quantitative analysis of myenteric plexus neurons in the small and large intestines of 120-day-old male GK rats was investigated. METHODS: The diabetes was confirmed by high fasting blood glucose levels. The myenteric plexus was evaluated through wholemount immunofluorescence. The morpho-quantitative analyses included evaluating neuronal density (neurons per ganglion) of the total neuronal population, the cholinergic and nitrergic subpopulations, and enteric glial cells per ganglion. The cell body area of 100 neurons per segment per animal was measured. RESULTS: The total neurons and nitrergic subpopulation were unaltered in the GK rats' small and large intestines. The cholinergic subpopulation exhibited decreased density in the three segments of the small intestine and an increased number in the proximal colon of the GK rats. The number of enteric glial cells increased in the ileum of the GK rats, which could indicate enteric gliosis caused by the intestinal inflammatory state. The area of the cell body was increased in the total neuronal population of the jejunum and ileum of the GK rats. Frequency histograms of the cell body area distribution revealed the contribution of cholinergic neurons to larger areas in the jejunum and nitrergic neurons in the ileum. CONCLUSION: The constipation previously reported in GK rats might be explained by the decrease in the density of cholinergic neurons in the small intestine of this animal model.


Assuntos
Motilidade Gastrointestinal , Plexo Mientérico , Animais , Plexo Mientérico/patologia , Masculino , Ratos , Neurônios Nitrérgicos/patologia , Neurônios Nitrérgicos/metabolismo , Neuroglia/patologia , Neuroglia/metabolismo , Diabetes Mellitus Tipo 2/patologia , Diabetes Mellitus Tipo 2/fisiopatologia , Neurônios Colinérgicos/patologia , Neurônios Colinérgicos/metabolismo , Neurônios/patologia , Neurônios/metabolismo , Modelos Animais de Doenças
4.
Cells ; 13(19)2024 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-39404410

RESUMO

Though the mechanisms are not fully understood, tryptophan (Trp) and physical exercise seem to regulate mechanical hypersensitivity in fibromyalgia. Here, we tested the impact of Trp supplementation and continuous low-intensity aerobic exercise on the modulation of mechanical hypersensitivity in a fibromyalgia-like model induced by acid saline in female rats. Twelve-month-old female Wistar rats were randomly divided into groups: [control (n = 6); acid saline (n = 6); acid saline + exercise (n = 6); acid saline + Trp (n = 6); and acid saline + exercise + Trp (n = 6)]. Hypersensitivity was caused using two intramuscular jabs of acid saline (20 µL; pH 4.0; right gastrocnemius), 3 days apart. The tryptophan-supplemented diet contained 7.6 g/hg of Trp. The three-week exercise consisted of progressive (30-45 min) treadmill running at 50 to 60% intensity, five times (Monday to Friday) per week. We found that acid saline induced contralateral mechanical hypersensitivity without changing the levels of Trp, serotonin (5-HT), and kynurenine (KYN) in the brain. Hypersensitivity was reduced by exercise (~150%), Trp (~67%), and its combination (~160%). The Trp supplementation increased the levels of Trp and KYN in the brain, and the activity of indoleamine 2,3-dioxygenase (IDO), and decreased the ratio 5-HT:KYN. Exercise did not impact the assessed metabolites. Combining the treatments reduced neither hypersensitivity nor the levels of serotonin and Trp in the brain. In conclusion, mechanical hypersensitivity induced by acid saline in a fibromyalgia-like model in female rats is modulated by Trp supplementation, which increases IDO activity and leads to improved Trp metabolism via the KYN pathway. In contrast, physical exercise does not affect mechanical hypersensitivity through brain Trp metabolism via either the KYN or serotonin pathways. Because this is a short study, generalizing its findings warrants caution.


Assuntos
Modelos Animais de Doenças , Fibromialgia , Condicionamento Físico Animal , Ratos Wistar , Serotonina , Triptofano , Animais , Triptofano/metabolismo , Triptofano/farmacologia , Fibromialgia/metabolismo , Feminino , Ratos , Serotonina/metabolismo , Cinurenina/metabolismo , Indolamina-Pirrol 2,3,-Dioxigenase/metabolismo , Hiperalgesia/metabolismo , Encéfalo/metabolismo , Encéfalo/efeitos dos fármacos , Encéfalo/patologia , Suplementos Nutricionais
5.
Cells ; 13(19)2024 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-39404421

RESUMO

Umbilical cord mesenchymal stem cell-derived extracellular vesicles (UC-EVs) are valuable in nanomedicine as natural nanocarriers, carrying information molecules from their parent cells and fusing with targeted cells. miRNA-126, specific to endothelial cells and derived from these vesicles, supports vascular integrity and angiogenesis and has protective effects in kidney diseases. OBJECTIVE: This study investigates the delivery of miRNA-126 and anti-miRNA-126 via UC-EVs as natural nanocarriers for treating nephrotoxic injury in vitro. METHOD: The umbilical cord-derived mesenchymal stem cell and UC-EVs were characterized according to specific guidelines. Rat kidney proximal tubular epithelial cells (tubular cells) were exposed to nephrotoxic injury through of gentamicin and simultaneously treated with UC-EVs carrying miRNA-126 or anti-miRNA-126. Specific molecules that manage cell cycle progression, proliferation cell assays, and newly synthesized DNA and DNA damage markers were evaluated. RESULTS: We observed significant increases in the expression of cell cycle markers, including PCNA, p53, and p21, indicating a positive cell cycle regulation with newly synthesized DNA via BrDU. The treatments reduced the expression of DNA damage marker, such as H2Ax, suggesting a lower rate of cellular damage. CONCLUSIONS: The UC-EVs, acting as natural nanocarriers of miRNA-126 and anti-miRNA-126, offer nephroprotective effects in vitro. Additionally, other components in UC-EVs, such as proteins, lipids, and various RNAs, might also contribute to these effects.


Assuntos
Vesículas Extracelulares , Células-Tronco Mesenquimais , Cordão Umbilical , Vesículas Extracelulares/metabolismo , Vesículas Extracelulares/transplante , Células-Tronco Mesenquimais/metabolismo , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/efeitos dos fármacos , Animais , Cordão Umbilical/citologia , Ratos , Humanos , Proliferação de Células/efeitos dos fármacos , MicroRNAs/metabolismo , MicroRNAs/genética , Ciclo Celular/efeitos dos fármacos , Dano ao DNA
6.
Molecules ; 29(19)2024 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-39407486

RESUMO

In this research, we aimed to determine the antioxidant activity of an atomized extract of Cnidoscolus diacanthus (Pax & K. Hoffm.) J.F. Macbr., known in Peru as "huanarpo hembra", and its effect on sex hormone levels. Its phytochemical profile was determined using liquid chromatography-mass spectrometry (LC-MS), while its total phenol content (TPC) and total flavonoids (TFs) were determined using the Folin-Ciocalteu method and the aluminum chloride method. Its antioxidant activity was determined using 2,2-diphenyl-1-picrylhydrazyl (DPPH), the radical 2,2-azino-bis-3-ethylbenzthiazolin-6 sulfonic acid (ABTS), and ferric-reducing antioxidant power (FRAP). The biological activity of C. diacanthus and its effect on sexual hormones were determined in Holtzman rats of both sexes. Phytochemical analysis revealed the presence of flavonoids and phenolic compounds in its leaves and stems, mainly rutin, quercetin, chlorogenic acid, and genistein. However, the stem extract contained higher total phenol (464.38 ± 4.40 GAE/g) and flavonoid (369.17 ± 3.16 mg QE/g of extract) contents than the leaf extract (212.38 ± 3.19 mg GAE/g and 121.49 ± 2.69 mg QE/g). For DPPH, ABTS, and FRAP, the Trolox-equivalent antioxidant capacity (TEAC) was 597.20 ± 5.40 µmol/g, 452.67 ± 5.76 µmol/g, and 535.91 ± 1.56 µmol/g, respectively, for the stems, while for the leaves, it was 462.39 ± 3.99 µmol/g, 202.32 ± 5.20 µmol/g, and 198.13 ± 1.44 µmol/g, respectively. In terms of the values for hormonal levels, at a dose of 100 mg/kg of the extract, testosterone levels of 1.430 ng/mL (with the leaf extract) and 1.433 ng/mL (with the stem extract), respectively, were found in the male rats. Regarding estradiol levels, in the female rats, these were 10.425 ng/mL (leaf extract) and 8.775 ng/mL (stem extract), while their levels of luteinizing hormone were 0.320 mIU/mL (leaf extract) and 0.273 mIU/mL (stem extract). For the follicle-stimulating hormone, levels of 0.858 mIU/mL (leaf extract) and 0.840 mIU/mL (stem extract) were found in the female rats, and levels of 0.220 mIU/mL (leaf extract) and 0.200 mIU/mL (stem extract) were found in the male rats. It is concluded that the C. diacanthus stem extract had a greater antioxidant capacity than the leaf extract, while both extracts had a superior effect on the sex hormone levels in the female rats compared to the male rats.


Assuntos
Antioxidantes , Extratos Vegetais , Folhas de Planta , Caules de Planta , Animais , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Folhas de Planta/química , Antioxidantes/farmacologia , Antioxidantes/química , Ratos , Masculino , Caules de Planta/química , Flavonoides/análise , Flavonoides/química , Flavonoides/farmacologia , Feminino , Peru , Hormônios Esteroides Gonadais/metabolismo , Fenóis/química , Fenóis/análise , Fenóis/farmacologia , Euphorbiaceae/química , Compostos Fitoquímicos/farmacologia , Compostos Fitoquímicos/química , Compostos Fitoquímicos/análise
7.
Molecules ; 29(19)2024 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-39407671

RESUMO

Wound healing is a complex and coordinated process involving interactions between cells and various messenger systems. This study conducted in vivo tests to determine the healing effect of propolis (PR)-based cream derived from the Amazon stingless bee, Scaptotrigona aff. postica, reared in açaí (Euterpe oleracea) monoculture, on induced wounds in rats. Data were obtained by monitoring injuries on 14 Wistar rats, divided into three groups (G1, G2 and G3), each receiving specific treatments: propolis-based cream (PR), collagenase (PC) and neutral cream (NC). Over the seven days of treatment, the lesions were measured using photographic records and ImageJ software to evaluate the healing effectiveness of the test cream. ImageJ software version 1.53g was used to compare the wound diameters for each treatment. After seven days, histopathological analyses of the induced lesions were performed. It was observed that collagenase (PC) and the test cream (PR) did not differ significantly in terms of wound diameter reduction. However, the propolis-based cream directly influenced the lesion maturation process and exhibited a milder inflammatory response compared to the positive control (PC). This effect is possibly associated with antimicrobial and anti-inflammatory compounds identified by GC/MS analysis in the propolis. Notably, this is the first report describing propolis of Scaptotrigona aff. postica obtained from açaí monocultures with strong healing potential, highlighting the identification of a high concentration of phenolic compounds that aid directly in wound repair.


Assuntos
Euterpe , Própole , Ratos Wistar , Cicatrização , Animais , Própole/farmacologia , Própole/química , Cicatrização/efeitos dos fármacos , Ratos , Abelhas , Euterpe/química , Masculino , Colagenases/metabolismo
8.
Int J Mol Sci ; 25(19)2024 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-39408569

RESUMO

Obesity causes insulin resistance (IR) through systemic low-grade inflammation and can lead to type 2 diabetes mellitus (T2DM). However, the mechanisms that cause IR and T2DM in non-obese individuals are unclear. The Goto-Kakizaki (GK) rat develops IR spontaneously and is a model of non-obese T2DM. These rats exhibit hyperglycemia beginning at weaning and exhibit lower body mass than control Wistar rats. Herein, we tested the hypothesis that macrophages of GK rats are permanently in a pro-inflammatory state, which may be associated with a systemic inflammation condition that mimics the pathogenesis of obesity-induced T2DM. Using eighteen-week-old GK and control Wistar rats, we investigated the proportions of M1 (pro-inflammatory) and M2 (anti-inflammatory) macrophages isolated from the peritoneal cavity. Additionally, the production of inflammatory cytokines and reactive oxygen species (ROS) in cultured macrophages under basal and stimulated conditions was assessed. It was found that phorbol myristate acetate (PMA) stimulation increased GK rat macrophage ROS production 90-fold compared to basal levels. This response was also three times more pronounced than in control cells (36-fold). The production of pro-inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α), tended to be upregulated in cultured macrophages from GK rats under basal conditions. Macrophages from GK rats produced 1.6 times more granulocyte-macrophage colony-stimulating factor (GM-CSF), 1.5 times more monocyte chemoattractant protein-1 (MCP-1) and 3.3 times more TNF-α than control cells when stimulated with lipopolysaccharide (LPS) (p = 0.0033; p = 0.049; p = 0.002, respectively). Moreover, compared to control cells, GK rats had 60% more M1 (p = 0.0008) and 23% less M2 (p = 0.038) macrophages. This study is the first to report macrophage inflammatory reprogramming towards a pro-inflammatory state in GK rats.


Assuntos
Diabetes Mellitus Tipo 2 , Inflamação , Macrófagos , Ratos Wistar , Espécies Reativas de Oxigênio , Animais , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/patologia , Diabetes Mellitus Tipo 2/imunologia , Ratos , Macrófagos/metabolismo , Macrófagos/imunologia , Espécies Reativas de Oxigênio/metabolismo , Inflamação/patologia , Inflamação/metabolismo , Masculino , Citocinas/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Modelos Animais de Doenças , Resistência à Insulina
9.
Acta Neurobiol Exp (Wars) ; 84(3): 275-287, 2024 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-39392023

RESUMO

The thalamic reticular nucleus controls information processing in thalamocortical neurons. GABAergic neurons present in this nucleus express the α3 subunit of post­synaptic GABAA receptors, which bind GABA from globus pallidus neurons. Pallidal neurons, in turn, have dopaminergic D4 receptors in their axon terminals. The thalamic reticular nucleus connects reciprocally with the thalamus, and it receives afferents from the brain cortex, as well as from other brain structures that have an important role in the modulation of the thalamic network. Based on the above, the purpose of this study was to assess the electrophysiological and molecular effects of unilateral lesion of the globus pallidus on the electric activity of the thalamic reticular nucleus. Two­month­old male rats were used. The right globus pallidus was lesioned with quinolinic acid. Seven days after the lesion, ipsilateral turning was registered, confirming the lesion. Afterward, electrophysiological evaluation of the right thalamic reticular nucleus' electrical activity was performed. Subsequently, mRNA expression for D4 receptors and subunit α3, as well as protein content were assessed in the right reticular nucleus. Pallidum lesion caused an increase in firing frequency and decreased firing bursts of reticular neurons. In addition, dopaminergic D4 mRNA, as well as protein increased. In contrast, GABAergic GABAA subunit α3 expression was suppressed, but protein content increased. These results show that the globus pallidus regulates firing in reticular neurons through D4 receptors and subunit α3 of GABAA receptor in the reticular nucleus of the thalamus.


Assuntos
Globo Pálido , Receptores de GABA-A , Animais , Masculino , Ratos , Potenciais de Ação/fisiologia , Globo Pálido/metabolismo , Neurônios/metabolismo , Ácido Quinolínico , Ratos Wistar , Receptores de Dopamina D4/metabolismo , Receptores de GABA-A/metabolismo , RNA Mensageiro/metabolismo , Núcleos Talâmicos/metabolismo
10.
PLoS One ; 19(10): e0311263, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39378196

RESUMO

We hypothesized that after synovial injury, collagen V (Col V) expose occult antigens, and Col V autoantibodies develop, indicating the loss of immune tolerance against this molecule, thus leading to damage to mesenchymal-derived cells as well as the extracellular matrix in experimental arthritis. Thus, the present study investigated the effects of oral administration of Col V on the synovium after the development of inflammation in mBSA/CFA-induced arthritis. After fourteen days of intraarticular administration of mBSA, 10 male Lewis rats were orally administered Col V (500 µg/300 µL) diluted in 0.01 N acetic acid (IA-Col V group). The arthritic group (IA group, n = 10) received only intraarticular mBSA. An intra-articular saline injection (20 µL) was given to the control group (CT-Col V, n = 5). IA group presented damaged synovia, the expansion of the extracellular matrix by cellular infiltrate, which was characterized by T and B lymphocytes, and fibroblastic infiltration. In contrast, after Col V oral immunotherapy IA-Col V group showed a significant reduction in synovial inflammation and intense expression of IL-10+ and FoxP3+ cells, in addition to a reduction in Col V and an increase in Col I in the synovia compared to those in the IA group. Furthermore, an increase in IL-10 production was detected after IA-Col V group spleen cell stimulation with Col V in vitro. PET imaging did not differ between the groups. The evaluation of oral treatment with Col V, after mBSA/CFA-induced arthritis in rats, protects against inflammation and reduces synovial tissue damage, through modulation of the synovial matrix, showing an immunotherapeutic potential in inhibiting synovitis.


Assuntos
Artrite Experimental , Colágeno Tipo V , Ratos Endogâmicos Lew , Membrana Sinovial , Animais , Masculino , Administração Oral , Ratos , Artrite Experimental/imunologia , Artrite Experimental/tratamento farmacológico , Artrite Experimental/patologia , Membrana Sinovial/imunologia , Membrana Sinovial/patologia , Colágeno Tipo V/imunologia , Colágeno Tipo V/administração & dosagem , Adjuvante de Freund/administração & dosagem , Imunoterapia/métodos , Interleucina-10 , Fatores de Transcrição Forkhead/metabolismo , Soroalbumina Bovina
11.
Braz J Biol ; 84: e286928, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39383417

RESUMO

Early postnatal administration of antibiotics has been linked to lasting effects on brain development and behavior. Research conducted on animals that are free from germs has demonstrated that the impact of microbiome colonization on the regulation of the hypothalamic-pituitary-adrenal (HPA) axis and neuroendocrine pathways is substantial, which play a crucial role in stress management. Nevertheless, it is still uncertain if the exposure to antibiotics in rat dams (F0-generation) before weaning is associated with neurobehavioral changes in rat offspring (F1-generation) during adulthood. In order to investigate the effects, we perturbed the intestinal microbiota of rat dams (F0 generation) by administering cefixime (CEF), an antibiotic commonly used for obstetric purposes, at clinically relevant doses (1 mg/kg, 2.5 mg/kg or 5 mg/kg). Anxiety-like behaviors in adult offspring was evaluated through the utilization of elevated plus maze (EPM) and open field paradigm (OFP) following a six-week interval from birth (PND42). Subsequent to behavioral assessments, the rats were euthanized, and their brains and blood was collected for biochemical analysis. Plasma corticosterone concentration was used to assess HPA activity, whereas the quantitative real-time polymerase chain reaction (PCR) was employed to determine the transcription levels of the glucocorticoid receptor (GR) Nr3c1. The offspring of F1 that were administered antibiotics before being weaned spent less time in the EPM open arm. The alterations were accompanied by increased levels of corticosterone in the bloodstream. The gene expression study revealed a decrease in the levels of mRNA transcription of Nr3c1. This research emphasizes the possible long-term effects of antibiotic exposure before weaning on the development of anxiety in offspring upon adulthood.


Assuntos
Antibacterianos , Ansiedade , Regulação para Baixo , Sistema Hipotálamo-Hipofisário , Sistema Hipófise-Suprarrenal , Ratos Wistar , Receptores de Glucocorticoides , Animais , Receptores de Glucocorticoides/metabolismo , Sistema Hipotálamo-Hipofisário/efeitos dos fármacos , Sistema Hipófise-Suprarrenal/efeitos dos fármacos , Feminino , Antibacterianos/farmacologia , Masculino , Regulação para Baixo/efeitos dos fármacos , Ratos , Corticosterona/sangue , Gravidez , Efeitos Tardios da Exposição Pré-Natal , Comportamento Animal/efeitos dos fármacos , Comportamento Animal/fisiologia , Teste de Campo Aberto/efeitos dos fármacos , Reação em Cadeia da Polimerase em Tempo Real , Animais Recém-Nascidos
12.
Acta Neurobiol Exp (Wars) ; 84(3): 266-274, 2024 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-39392022

RESUMO

Evidence is provided that the glycosylated flavonoid vitexin (apigenin­8­C­beta­D­glucopyranoside) attenuates pentylenetetrazole (PTZ)­induced acute tonic­clonic seizures in rats. However, the effects of chronic and systemic vitexin in PTZ­kindled rats remain unknown. The aim of this work was to investigate the effect of long­term treatment with vitexin in the PTZ­kindling model of epilepsy. Male Wistar rats received intraperitoneal injections of PTZ at a subconvulsive dose of 35 mg/kg every other day for 29 days. Either saline containing dimethyl sulfoxide - DMSO 1%  (vehicle), diazepam (2 mg/kg; positive control) or vitexin (2.5 mg/kg) was administered intraperitoneally 30 min before each PTZ injection. The behavioral reactions were recorded by 30 min immediately after each PTZ injection. Furthermore, on the 31st day, that is, 48 h after the latter dose of PTZ, the animals were euthanized and renal and hepatic biochemical markers were evaluated in blood serum. Chronic treatment with either diazepam or vitexin attenuated the seizures provoked by PTZ injections. Neither diazepam nor vitexin caused changes in renal levels of creatinine and urea and in hepatic levels of aspartate aminotransferase and alanine aminotransferase. Our findings suggest that chronic administration of vitexin attenuates the progression of PTZ­induced kindling without causing side effects on kidneys and liver.


Assuntos
Anticonvulsivantes , Apigenina , Diazepam , Excitação Neurológica , Pentilenotetrazol , Ratos Wistar , Convulsões , Animais , Masculino , Apigenina/farmacologia , Anticonvulsivantes/farmacologia , Excitação Neurológica/efeitos dos fármacos , Diazepam/farmacologia , Convulsões/tratamento farmacológico , Convulsões/induzido quimicamente , Modelos Animais de Doenças , Ratos , Fatores de Tempo , Convulsivantes/toxicidade , Epilepsia/tratamento farmacológico , Epilepsia/induzido quimicamente
13.
J Med Microbiol ; 73(10)2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39392377

RESUMO

Introduction. Tissue conditioners modified with antifungals are a potential alternative to denture stomatitis (DS) treatment.Gap Statement. Information on tissue response to this treatment before its clinical application is lacking.Aim. This study aimed to evaluate the tissue response of a tissue conditioner modified with antifungals in a rat model of DS.Methodology. After DS induction for 4 days under antibiotic therapy, Wistar rats had their intraoral devices (IODs) relined with the tissue conditioner Softone without (Soft) or with the MICs against Candida albicans of nystatin (Nys) or chlorhexidine (Chx) complexed or not with ß-cyclodextrin (Nys:ßCD and Chx:ßCD). Three controls were included: healthy rats [negative control (Nc)], rats using a sterile IOD [sterile device (Sd)] and rats with DS that did not receive treatment (DS). After 4 days of treatment, the palatal mucosa under the IODs underwent histological processing for morphohistopathological and histometric analyses, morphology of collagen fibres (birefringence), immunohistochemistry for the expression of cell proliferation (proliferating cell nuclear antigen) and cytokine (IL-1ß).Results. The Nc and Sd groups were similar (P>0.05), displaying epithelial and connective tissues without any discernible changes in the parameters assessed. The DS and Soft groups exhibited pronounced epithelial alterations, cell proliferation and expression of the cytokine IL-1ß. In groups treated with drug incorporation (Nys, Chx, Nys:ßCD and Chx:ßCD), all samples demonstrated a reduction in tissue inflammation or complete tissue recovery, with an epithelium compatible with health. For the immunohistochemical parameters, the Chx, Nys:ßCD and Chx:ßCD groups were comparable with Nc (P>0.05).Conclusion. The proposed treatment could be promising for DS, as it led to the tissue recovery of the palatal mucosa. Nevertheless, much lower concentrations of complexed antifungals were required to achieve a similar or higher degree of tissue response compared with uncomplexed drugs in a modified tissue conditioner formulation.


Assuntos
Antifúngicos , Candida albicans , Modelos Animais de Doenças , Mucosa Bucal , Nistatina , Ratos Wistar , Estomatite sob Prótese , beta-Ciclodextrinas , Animais , beta-Ciclodextrinas/química , Antifúngicos/farmacologia , Estomatite sob Prótese/tratamento farmacológico , Estomatite sob Prótese/microbiologia , Ratos , Nistatina/farmacologia , Nistatina/administração & dosagem , Candida albicans/efeitos dos fármacos , Mucosa Bucal/efeitos dos fármacos , Mucosa Bucal/microbiologia , Masculino , Clorexidina/farmacologia , Interleucina-1beta/metabolismo , Antígeno Nuclear de Célula em Proliferação/metabolismo , Testes de Sensibilidade Microbiana
14.
Sci Rep ; 14(1): 23689, 2024 10 10.
Artigo em Inglês | MEDLINE | ID: mdl-39390131

RESUMO

Chronic liver disease is closely linked to dietary intake factors, such as high consumption of simple carbohydrates including sucrose. In this study, the influence of sucrose on the development of hepatocellular carcinoma (HCC), the most common primary liver malignancy, was explored. Using the hepatocarcinogen diethylnitrosamine (DEN) to induce HCC in the rat, we co-administered sucrose with DEN. The co-administration significantly modified body, liver and pancreas weight, as well as, serum fatty acids and triglycerides. DEN caused liver structural alteration, fibrosis, and tumor formation; surprisingly, co-administration with sucrose restored hepatic lipids, improved liver architecture, and reduced fibrosis and tumor development. Sucrose intake negatively regulated tumor markers and cell proliferation, and reduced the expression of genes associated with lipid metabolism and oxidative stress response. These findings highlight a hepatoprotective effect of sucrose during DEN-induced hepatocarcinogenesis, underlining an intriguing role of high sucrose consumption during HCC development and providing new insights as well as possible pathways of cellular protection under sucrose intake on hepatocarcinogenesis.


Assuntos
Carcinoma Hepatocelular , Dietilnitrosamina , Neoplasias Hepáticas , Sacarose , Animais , Carcinoma Hepatocelular/induzido quimicamente , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/prevenção & controle , Sacarose/efeitos adversos , Sacarose/farmacologia , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/induzido quimicamente , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/prevenção & controle , Ratos , Masculino , Dietilnitrosamina/toxicidade , Fígado/metabolismo , Fígado/patologia , Fígado/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Metabolismo dos Lipídeos/efeitos dos fármacos , Substâncias Protetoras/farmacologia
15.
Braz J Med Biol Res ; 57: e13116, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39383377

RESUMO

Nephrotoxicity is a common complication that limits the clinical utility of cisplatin. Ferroptosis is an iron-dependent necrotic cell death program that is mediated by phospholipid peroxidation. The molecular mechanisms that disrupt iron homeostasis and lead to ferroptosis are yet to be elucidated. In this study, we aimed to investigate the involvement of nuclear receptor coactivator 4 (NCOA4), a selective cargo receptor that mediates ferroptosis and autophagic degradation of ferritin in nephrotoxicity. Adult male Sprague-Dawley rats were randomly-assigned to four groups: control group, cisplatin (Cis)-treated group, deferiprone (DEF)-treated group, and Cis+DEF co-treated group. Serum, urine, and kidneys were isolated to perform biochemical, morphometric, and immunohistochemical analysis. Iron accumulation was found to predispose to ferroptotic damage of the renal tubular cells. Treatment with deferiprone highlights the role of ferroptosis in nephrotoxicity. Upregulation of NCOA4 in parallel with low ferritin level in renal tissue seems to participate in iron-induced ferroptosis. This study indicated that ferroptosis may participate in cisplatin-induced tubular cell death and nephrotoxicity through iron-mediated lipid peroxidation. Iron dyshomeostasis could be attributed to NCOA4-mediated ferritin degradation.


Assuntos
Cisplatino , Ferroptose , Coativadores de Receptor Nuclear , Ratos Sprague-Dawley , Transdução de Sinais , Animais , Ferroptose/efeitos dos fármacos , Masculino , Cisplatino/toxicidade , Coativadores de Receptor Nuclear/metabolismo , Transdução de Sinais/efeitos dos fármacos , Ratos , Deferiprona/farmacologia , Sistema y+ de Transporte de Aminoácidos/metabolismo , Antineoplásicos , Peroxidação de Lipídeos/efeitos dos fármacos , Ferro/metabolismo , Rim/efeitos dos fármacos , Rim/metabolismo , Rim/patologia , Ferritinas/metabolismo , Nefropatias/induzido quimicamente , Nefropatias/metabolismo , Imuno-Histoquímica
16.
Acta Cir Bras ; 39: e397024, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39383420

RESUMO

PURPOSE: This study aimed to evaluate the effects of ozone therapy applied topically and/or by bagging on the healing of clean wounds induced in rat's skin. METHODS: One hundred and twenty male rats of about 16 weeks old was divided into five groups: G1) saline solution (0.9%); G2) sunflower oil; G3) ozonated sunflower oil; G4) ozone bagging; G5) association of ozonated sunflower oil and ozone bagging. The wounds were evaluated through macroscopic, morphometric, histopathologic, and tensile strength analyses. RESULTS: Analysis among groups showed a lower percentage of wound contraction in G1 compared to G4 only in M7D. The tensile strength of the wounds showed differences among groups in the seventh (M7D) and the 14th (M14D) postoperative day, and among time points in G1 (M14D > M7D). The elongation of the wounds showed differences in G3 (M7D > M14D). Histological evaluation of the wounds showed significant change in bleeding, mixed to mononuclear infiltrate, congestion, and tissue disorganization for tissue organization between groups and time points. CONCLUSIONS: Ozone therapy applied topically and/or by bagging was not deleterious to the healing of clean wounds induced in rat's skin, but ozone bagging showed the best contribution to the healing process.


Assuntos
Ozônio , Ratos Wistar , Pele , Resistência à Tração , Cicatrização , Animais , Ozônio/administração & dosagem , Ozônio/uso terapêutico , Ozônio/farmacologia , Cicatrização/efeitos dos fármacos , Masculino , Pele/lesões , Pele/efeitos dos fármacos , Pele/patologia , Ratos , Resistência à Tração/efeitos dos fármacos , Óleo de Girassol , Administração Tópica , Fatores de Tempo , Resultado do Tratamento , Modelos Animais de Doenças , Reprodutibilidade dos Testes
17.
Sci Rep ; 14(1): 23567, 2024 10 09.
Artigo em Inglês | MEDLINE | ID: mdl-39384890

RESUMO

Brain death (BD) provides most of the donor organs destined for lung transplantation (LTx). However, the organs may be affected by inflammatory and oxidative processes. Based on this, we hypothesize that the angiotensin-converting enzyme 2 (ACE2) activation can reduce the lung injury associated with LTx. 3 h after BD induction, rats were injected with saline (BD group) or an ACE2 activator (ACE2a group; 15 mg/kg-1) and kept on mechanical ventilation for additional 3 h. A third group included a control ventilation (Control group) prior to transplant. After BD protocol, left LTx were performed, followed by 2 h-reperfusion. ACE2 activation was associated with better oxygenation after BD management (p = 0.01), attenuating edema (p = 0.05) followed by the reduction in tissue resistance (p = 0.01) and increase of respiratory compliance (p = 0.02). Nrf2 expression was also upregulated in the ACE2a group (p = 0.03). After transplantation, ACE2a group showed lower levels of TNF-α (p = 0.02), IL-6 (p = 0.001), IL-1ß (p = 0.01), ROS (p = 0.004) and MDA (p = 0.002), in addition to higher CAT activity (p = 0.04). In conclusion, our study suggests that ACE2 activation improves anti-inflammatory and antioxidant activity in a model of LTx.


Assuntos
Enzima de Conversão de Angiotensina 2 , Morte Encefálica , Inflamação , Transplante de Pulmão , Estresse Oxidativo , Animais , Enzima de Conversão de Angiotensina 2/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Transplante de Pulmão/efeitos adversos , Ratos , Inflamação/metabolismo , Masculino , Peptidil Dipeptidase A/metabolismo , Doadores de Tecidos , Pulmão/metabolismo , Pulmão/patologia
18.
Acta Cir Bras ; 39: e396524, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39356933

RESUMO

PURPOSE: This work aimed to investigate the effects of Tanshinone IIA (Tan IIA) on myocardial cell (MC) apoptosis in a rat model of heart failure (HF). METHODS: Tan IIA was extracted from Salvia miltiorrhiza Bunge (SMB) using an ethanol reflux method. Fifty rats were randomly divided into five groups: sham (no treatment), mod (HF model establishment), low dose (LD: 0.1 mL/kg Tan IIA), medium dose (MD: 0.3 mL/kg Tan IIA), and high dose (HD: 0.5 mL/kg Tan IIA), with 10 rats in each group. The effects of different doses of Tan IIA on cardiac function, MC apoptosis, and the levels of proteins associated with the PI3K/Akt/mTOR signaling pathway were compared. RESULTS: Mod group showed a significant decrease in systolic arterial pressure, mean arterial pressure, heart rate, left ventricular systolic pressure, left ventricular ejection fraction, left ventricular fractional shortening, and the levels of p-PI3K, p-Akt, and p-mTOR proteins versus sham group (p < 0.05). Additionally, the left ventricular end-diastolic diameter (LVIDd), end-systolic diameter, diastolic pressure, and MC apoptosis were significantly increased (p < 0.05). LD, MD, and HD groups exhibited significant improvements across various indicators of cardiac function and MC apoptosis versus mod group (p < 0.05). CONCLUSIONS: Tan IIA may improve cardiac function and inhibit MC apoptosis in rats with HF by modulating the PI3K/Akt/mTOR signaling pathway.


Assuntos
Abietanos , Apoptose , Modelos Animais de Doenças , Insuficiência Cardíaca , Miócitos Cardíacos , Salvia miltiorrhiza , Animais , Apoptose/efeitos dos fármacos , Salvia miltiorrhiza/química , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/fisiopatologia , Masculino , Abietanos/farmacologia , Abietanos/uso terapêutico , Miócitos Cardíacos/efeitos dos fármacos , Distribuição Aleatória , Transdução de Sinais/efeitos dos fármacos , Ratos Sprague-Dawley , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Proto-Oncogênicas c-akt/efeitos dos fármacos , Ratos , Serina-Treonina Quinases TOR/metabolismo , Serina-Treonina Quinases TOR/efeitos dos fármacos , Fosfatidilinositol 3-Quinases/metabolismo , Reprodutibilidade dos Testes
19.
Acta Cir Bras ; 39: e396924, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39356936

RESUMO

PURPOSE: Tamoxifen, a widely used drug for breast cancer treatment, is associated with adverse effects on the liver, including the development of fatty liver. This study aimed to investigate the potential protective effect of caffeine against tamoxifen-induced fatty liver in Wistar rats. METHODS: Rats were divided into normal control, tamoxifen + saline, and tamoxifen + caffeine. Plasma samples were assessed for biochemical markers related to oxidative stress, inflammation, liver function, and cell damage. Additionally, liver histopathology was examined to quantify the extent of fatty infiltration. RESULTS: In the tamoxifen + saline group, elevated levels of plasma malondialdehyde (MDA), tumor necrosis factor-alpha (TNF-α), alanine aminotransferase (ALT), cytokeratin 18, and soluble ST2 were observed compared to the normal control group, indicating increased oxidative stress, inflammation, and liver injury (p < 0.01). Moreover, histopathological examination revealed a significant increase in fatty infiltration (p < 0.001). However, in the tamoxifen + caffeine group, these markers were markedly reduced (p < 0.05, p < 0.01), and fatty infiltration was significantly mitigated (p < 0.001). CONCLUSIONS: The findings suggest that caffeine administration attenuates tamoxifen-induced fatty liver in rats by ameliorating oxidative stress, inflammation, liver injury, and cell damage. Histopathological evidence further supports the protective role of caffeine. This study highlights the potential of caffeine as a therapeutic intervention to counter tamoxifen-induced hepatic complications, contributing to the optimization of breast cancer treatment strategies.


Assuntos
Cafeína , Fígado Gorduroso , Malondialdeído , Estresse Oxidativo , Ratos Wistar , Tamoxifeno , Animais , Cafeína/farmacologia , Cafeína/uso terapêutico , Tamoxifeno/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Malondialdeído/análise , Fígado Gorduroso/induzido quimicamente , Fígado Gorduroso/prevenção & controle , Fígado Gorduroso/tratamento farmacológico , Feminino , Fígado/efeitos dos fármacos , Fígado/patologia , Alanina Transaminase/sangue , Ratos , Antineoplásicos Hormonais/farmacologia , Fator de Necrose Tumoral alfa/sangue , Fator de Necrose Tumoral alfa/análise , Biomarcadores/sangue , Biomarcadores/análise , Modelos Animais de Doenças
20.
Acta Cir Bras ; 39: e396724, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39356935

RESUMO

PURPOSE: To describe an experimental surgical model in rats using a dual-plane technique for evaluation of biomaterials in an in-vivo silicone implant coverage. METHODS: This study was developed following the ISO 10993-6 standard. In this study, 40 male Wistar rats weighing between 250 and 350 g were used, distributed into two groups: experimental, biomaterial superimposed on the minimammary prosthesis (MP); and control, MP without implantation of the biomaterial, with eight animals at each biological point: 1, 2, 4, 12, and 26 weeks. Thus, at the end of biological points (1, 2, 4, 12, and 26 weeks; n = 8 animals per week), the tissue specimens achieved were fixed in buffered formalin and stained with hematoxylin-eosin. RESULTS: Macroscopically, throughout the study, no postoperative complications were apparent. In the histological analysis, it was possible to observe the evolution of the inflammatory response, tissue repair, and fibrous capsule during the biological points. CONCLUSIONS: The experimental model described in this study proved to be suitable for evaluating the biomaterial used in the coverage of breast silicone implants.


Assuntos
Materiais Biocompatíveis , Implantes de Mama , Ratos Wistar , Géis de Silicone , Animais , Masculino , Ratos , Teste de Materiais , Modelos Animais , Silicones , Fatores de Tempo
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